IJSIR Vol.5 Issue (ii)

VOLUME – 5, ISSUE – 2 (JULY-DECEMBER) 2017

Editorial
I am happy to convey that second issue of third volume of "International Journal of Scientific
and Innovative Research (IJSIR)", a bi-annual journal has been published by Sky Institute,
Lucknow in an effort to promote multidisciplinary scientific and innovative research of
societal benefit. This journal covers all branches of science, technology, engineering, health,
agriculture and management. Research articles in the field of education are also encouraged in
order to promote educational technology aiming at improvement in present educational
system. As research and development (R & D) has been playing a significant role in overall
development of society, continuous multidisciplinary innovative research in science and
technology is needed to address the challenges in context to changing environmental
conditions in the present era of gradual increase in industrial and technological advancement
at global level. Efforts should be made to develop eco-friendly technologies in order to
providesolutionsfordevelopingsocially,economicallyandculturallysustainablesociety.
The present issue of International Journal of Scientific and Innovative Research (IJSIR)
contains 18 research papers I articles covering different areas of science and technology. All
these papers are well written and informative in content. I express my thanks to members of
Committee for EditorialAssistance Dr. B.C.Tripathi, Dr. Pankaj Verma, Shri Sanjay Pandey,
Shri Sanjay Dixit and Mr. Shamshul Hasan Khan for their hard work and devotion in giving
the final shape to the journal. I am thankful to all faculty members, scientists and research
scholars of different universities, research organizations and technical institutions for
contributing their research articles for publication in the present issue of the journal. The help
provided by faculty members and supporting staff of Sky Institute in publishing the present
volume of the journal is also acknowledged. I hope scientists, academicians and young
researcherswillbegreatlybenefitedbythispublicationfortheirresearchwork.
I request humbly to the readers and contributors of our journal to continue encouraging us for
regular publication of the journal. Any suggestion and comment for the improvement in the
qualityofthejournalarealwayswelcome.
Dr. B. R. Pandey
Editor-in-Chief

EDITOR-IN-CHIEF
Dr. B.R. Pandey
Director (Research)
Sky Institute, Kursi Road, Lucknow, U.P, India
Dean, Faculty of Science & Technology, Sai Nath University, Jharkhand, India
Former Joint Director, Council of Science & Technology, UP, Lucknow
(Department of Science and Technology, UP Government), India
Former Professor, International Institute of Herbal Medicine (IIHM), Lucknow, U.P., India
E-mail Id: editorijsir02@gmail.com, Mobile-: 9794849800
COMMITTEE FOR EDITORIALASSISTANCE
Dr. B.C.Tripathi
Assistant Prof., Deptt. of Education,
Rama P.G. College, Chinhat,
Lucknow, Uttar Pradesh
Dr. Pankaj Verma
Senior Research Fellow, Deptt. of
Oral & Maxillofacial Surgery, Faculty
of Dental Sciences, K.G. Medical
University, Lucknow, Uttar Pradesh
Shri Sanjay Pandey
Assistant Prof., National Institute
of Fashion Technology, Raebareli,
Uttar Pradesh
Shri Ashish Tiwari
Research Scholar, Sai Nath University,
Ranchi, Jharkhand
Shri Sanjay Dixit
Scientist, Sky Institute, Lucknow,
Uttar Pradesh
Shamshul Hasan Khan
Scientist, Sky Institute, Lucknow,
Uttar Pradesh
ADVISORY BOARD
Prof.(Dr.)S. P. Ojha
Former Vice Chancellor, CCS Meerut University, Meerut, Uttar Pradesh
Prof.(Dr.)V.K. Srivastava
Former Prof & Head, Deptt. of Community Medicine King George Medical
University, Lucknow.
Former Director, Integral Institute of Medical Sciences & Research, Integral
University, Lucknow
Former Vice -Chancellor,
Texila American University, Georgetown, Guyana, South America
Prof.(Dr.) M.I. Khan
Prof & Head, Deptt. of Mechanical Engg., Integral University, Lucknow, Uttar
Pradesh
Prof. (Dr.) S.K. Avasthi
Former Director, H.B.T.I., Kanpur, Uttar Pradesh
Prof.(Dr.) Amrika Singh
Prof & Head (Chemistry), Deptt. of Applied Sciences,
Institute of Engg. & Technology, Sitapur Road, Lucknow, Uttar Pradesh
Prof. (Dr.) U.N. Dwivedi
Prof & Ex- Head, Deptt of Biochemistry, Former Pro- Vice Chancellor, Former
Dean, Faculty of Science, University of Lucknow, Lucknow, U.P.
Prof. (Dr.) U.K. Misra
Head, Deptt. of Neurology, Ex Dean,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, U.P.
Dr. A.K. Gupta
Former Deputy Director General,
Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi
Prof.(Dr.) V.K.Tondon
Former Prof & Head, Deptt. of Chemistry, Ex- Dean Faculty of Science,
University of Lucknow, Lucknow, Uttar Pradesh
Prof. (Dr.) Amod Kumar Tiwari,
Prof.- Director, Bhabha Institute of Engg.& Technology, Kanpur, U.P.
Prof.(Dr.) Chandra Dhar Dwivedi
Former Prof. & Chairman, Deptt. of Pharmaceutical Sciences, College of
Pharmacy, South Dakota State University, Borokings, South Dakota, USA
Prof. (Dr.) Vimal Kishore
Prof. & Chairman, Deptt. of Basic Pharmaceutical Sciences,
Xevier College of Pharmacy, University of Louisiana, 7325, Palmetto Street
New Orlens, Louisiana USA
Prof. (Dr.) S.P. Singh
Former Prof & Head, Deptt. of Pharmacology,
G. S. V. M. Medical College, Kanpur, Uttar Pradesh
Prof. (Dr.) R. L. Singh
Prof & Head, Department of Biochemistry & Coordinator Biotechnology
Program , Dr. R. M. L. University Faizabad, Uttar Pradesh
Dr. Sarita Verma
Head, Deptt. of Home Sci., Mahila P.G. College, Kanpur, Uttar Pradesh
Prof. (Dr.) S.K.Agarwal
Pro. & Ex-Head, Deptt. of Biochemistry, Lucknow University, Lucknow,
U.P.
Dr. Bharat Sah
Director,
National Institute of Fashion Technology, Raebareli, Uttar Pradesh
Prof. (Dr.)N.S. Verma
Prof., Deptt. of Physiology,
K. G. Medical University, Lucknow, Uttar Pradesh
Prof. (Dr.)A.K. Tripathi
Prof. & Head, Deptt. of Clinical Hematology & Medical Oncology,
Prof.(Dr.)C.M. Pandey
Prof. & Head, Deptt. of Biostatistics & Health Informatics,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow,
Uttar Pradesh
Dr. Rupesh Chaturvedi
Associate Prof., School of Biotechnology,
Jawaharlal Nehru University, New Delhi, Former Asstt. Prof., Deptt. of
Pharmaceutical Sciences , College of Pharmacy, Vanderbilt University,
Tennessee, USA
Dr. S.Sinha
Asstt. Prof. Deptt. of Internal Medicine, CD University,
C. David Giffen School of Medi., University of California, Los Angeles, USA
Dr. K.Raman
Principal Scientist, Martek Biosciences Corporation, 6480 Dobbin Road,
Columbia, MD 21045, USA Dr. P.K.Agarwal
Editor –in – Chief, Natural Product Communication,
Natural Product Inc 7963, Anderson Park Lane West Terville, OH, USA
Dr. R.K.Singh,
Chief Scientist, Division of Toxicology, CSIR-Central Drug Research
Institute, Jankipuram Extension, Lucknow, Uttar Pradesh
Dr. Mohd. Tarique
Prof., Deptt of Physical Edu., Lucknow University, Lucknow, Uttar Pradesh
International Journal of Scientific and Innovative Research 2017; 5(2)
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EDITORIAL BOARD
Prof.(Dr.) Y.B. Tripathi
Prof. & Head, Deptt. of Medicinal Chemistry,Institute of Medical Sciences, Banaras
Hindu University Varanasi, Uttar Pradesh
Prof.(Dr.) R.K. Singh
Prof. & Head , Deptt. of Biochemistry, Shri Guru Ram RaiInstitute of Medical & Health
Sciences, Dehradun, Uttarakhand & Former Prof. & Head, Department of Biochemistry,
K. G. Medical University, Lucknow, U.P.
Prof. (Dr.) R.S.Diwedi
Former Director, National Research Centre for Groundnut (NRCG) , ICAR, Junagarh,
Gujarat & Former Principal Scientist – Head, Deptt. of Plant Physiology, Indian Institute
of Sugarcane Research, Lucknow, Uttar Pradesh
Prof. (Dr.) Nuzhat Husain
Prof. & Head , Deptt of Pathology & Acting Director, R. M. L. Institute of Medical
Sciences, Lucknow,Uttar Pradesh
Prof. (Dr.) Amita Jain
Prof. Deptt. of Microbiology, K.G. Medical University, Lucknow, U.P.
Dr. Sudhir Mahrotra
Associate Prof., Deptt. of Biochemistry, Lucknow University, Lucknow, U.P.
Prof. (Dr.) Vibha Singh
Prof., Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental Sciences,
Prof. (Dr.) U.S. Pal
Prof. & Head, Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental Sciences,
Prof. (Dr. ) K.K. Pant
Prof. & Head, Deptt. of Pharmacology & Therapeutics,
Dr. C.M.K.Tripathi
Former Deputy Director & Head, Division of Fermentation Technology, CSIR- Central
Drug Research Institute , Lucknow, Uttar Pradesh
Dr. R.D. Tripathi
Chief Scientist & ProfessorPlant Ecology & Environmental Science Division, Uttar
Pradesh CSIR-National Botanical Research Institute, Lucknow, U.P.
Prof.(Dr.) Ashwani K. Srivastav
Prof. & Head, Deptt. of Biosciences, Integral University,Lucknow,
Former Senior Scientist, Birbal Sbahani Institute Paleobotany, Lucknow, U.P.
Prof.(Dr.) L. Pandey
Prof. & Head , Postgraduate Deptt . of Physics,Former Dean, Faculty of Science, Rani
Durgawati University, Jabalpur, Madhya Pradesh, India
Prof .(Dr.) Bali Ram
Prof., Deptt. of Chemistry, Banaras Hindu University, Varanasi, Uttar Pradesh
Prof.(Dr.) J.P.N.Rai
Prof.& Head, Deptt. of Environmental Sciences, G.B. Pant University of Agr. &
Technology, Pant Nagar, Uttarakhand
Prof.(Dr. )R. S. Dubey
Prof. & Head, Deptt. of Biochemistry, Banaras Hindu University, Varanasi, U.P.
Prof. (Dr.) Omkar
Deptt. of Zoology, Lucknow University, Lucknow, Uttar Pradesh
Prof.(Dr.) Sudhir Kumar
Prof., Deptt. of Zoology, Lucknow University, Lucknow, Uttar Pradesh
Prof.(Dr.) Naveen Khare
Prof., Deptt. of Chemistry, Lucknow University, Lucknow, Uttar Pradesh
Prof.(Dr.) S. M. Natu
Prof., Deptt. of Pathalogy,K.G. Medical University, Lucknow, Uttar Pradesh
Dr. Kusum Lata Mishra,
In-charge, Coagulation Laboratory, Deptt. of Pathology,
K.G. Medical University, Lucknow, Uttar Pradesh
Prof.(Dr.)V.K. Sharma,
Prof., Deptt. of Chemistry, Lucknow University, Uttar Pradesh
Prof.(Dr.) R.K. Shukla
Prof., Deptt. of Physics, Lucknow University, Lucknow Uttar Pradesh
Prof.(Dr.)Anil Gaur
Prof., Deptt. of Biotechnology & Genetic Engg., G.B. Pant University of Agr. &
Technology, Pant Nagar, Uttarakhand
Dr. Mahesh Pal
Principal Scientist ,Phytochemistry Division, CSIR- National Botanical Research
Institute, Lucknow, Uttar Pradesh
Dr. Vinod Singh
Assoc. Prof. & Head, Deptt. of Microbiology, Baruktulla University, Bhopal, M.P.
Dr. Anchal Srivastava,
Prof., Deptt of Physics, Lucknow University,Lucknow, Uttar Pradesh
Dr. K.K.Verma
Assoc. Prof., Deptt. of Physics & Electronics.Dr. R. M. L. Awadh University ,
Faizabad,Uttar Pradesh
Dr. Atul Gupta
Senior Scientist, CSIR- Central Institute of Medicinal & Aromatic Plants,
Dr. Saudan Singh,
Senior Principal Scientist, CSIR- Central Institute of Medicinal & Aromatic
Plants , Lucknow, Uttar Pradesh
Dr. S.K.Tiwari
Senior Principal Scientist ,CSIR- National Botanical Research Institute,
Dr. Shivani Pandey,
Asstt. Prof., Deptt. of Biochemistry,K.G.Medical University, Lucknow, U.P.
Dr. B.C. Yadav,
Lucknow Associate Prof. & Coordinator, Deptt. of Applied Physics, School for
Physical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, U.P.
Dr. Shalini Bariar
Associate Professor, Thakur Institute of Management Studies and
Research,, Mumbai, India
Dr.A.K.Pandey
Principal Scientist, National Bureau of Fish Genetic Resources,Lucknow, U.P.
Dr.S.K.Pandey
G.M. LML Factory, Kanpur Uttar Pradesh
Dr. Suneet Kumar Awasthi,
Asst. Prof, Deptt.of Physics J.P. University, Noida, Uttar Pradesh
Dr.G. N. Pandey
Asst. Prof, Deptt. of Physics Amity University, Noida ,Uttar Pradesh
Dr. Mukesh Verma
Asst. Prof., Deptt. of Physical Education, Dr. R.M.L. Avadh University,
Faizabad, Uttar Pradesh
Dr. Abhay Singh,
Head, Physical Education, Delhi Public School, Lucknow Uttar Pradesh
Dr. Santosh Gaur
Asst. Prof. Deptt. of Physical Education, Jawahar Lal Nehru P.G. College,
Barabanki, Uttar Pradesh
Dr.Sanjeev Kumar Jha
Senior Scientist, DEOACC Patna
Dr. Shivlok Singh
Scientist, DEOACC, Lucknow, Uttar Pradesh
Dr. Anurag Tripathi,
Asstt . Prof. , Deptt. of Electrical Engg., Institute of Engg. & Technology,
Sitapur Road, Lucknow, Uttar Pradesh
Prof. V.P.Sharma
Senior Principal Scientist, CSIR-Indian Institute of Toxicology Research,
Dr. Krishna Gopal
Former Deputy Director & Head , Aquatic Toxicology Division, CSIR- Indian
Institute of Toxicology Research, Lucknow, Uttar Pradesh
Dr. S.P. Shukla
Prof. , Deptt. of Civil Engg., Institute of Engg. & Technology, Sitapur Road ,
Dr. Ajay Mishra
Associate Prof. , Deptt. of Geology, Lucknow University, Lucknow , U. P.
Dr. Ashutosh Singh
Prof., Deptt. of Chemistry,Saket P.G. College, Ayodhya, Faizabad, U. P.
Dr. S.K. Singh
Principal, Gita College of Education , Nimbari, Panipat, Haryana
Shri Sudesh Bhat
Advisor (Education), Sky Institute, Lucknow, Uttar Pradesh
Dr. Krishna Gopal
Asst. Prof., Deptt. of English,Rama University, Kanpur, Uttar Pradesh
Dr. Chandra K. Dixit
Department of Physics Professor &Dean, Faculty of Science & Technology
Dr. Shakuntala Misra National Rehablitationuniversity,Lucknow
Professor (Dr.) Vivek Mishra
Director, ITM School of Management,Lucknow,U.P.,India
Anuj Kumar Gupta
Assistant Professor, ITM School of Management,Lucknow,U.P.,India
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ABOUT EDITOR-IN- CHIEF : DR. B. R. PANDEY
Dr. B. R. Pandey is a well-known academician and scientist with brilliant academic career and research
accomplishments. He has done M.Sc. (organic chemistry) from Banaras Hindu University,Varanasi, India in
the year 1972. He has done PhD in Medicinal Chemistry under the guidance of world renowned Biochemist
& Medicinal Chemist, Professor S.S. Parmar, Professor of Medicinal Chemistry & Chemical Pharmacology,
Department of Pharmacology & Therapeutics, K. G. Medical College, Lucknow (Presently K. G. Medical
University), Faculty of Medicine, University of Lucknow, Lucknow, India in the year 1976. Dr. Pandey has
all throughout first class educational qualifications and his research interest covers medicinal chemistry,
biochemical pharmacology, neurochemistry, neuro-toxicology, environmental chemistry, herbal medicine
& natural products. He is having extensive research experience of more than 40 years and published several
research papers in peer reviewed journals of international repute. His research particularly on the studies of
central nervous system acting drugs and anti-inflammatory drugs and their biochemical mode of action
using animal models and enzymes such as monoamine oxidase, acetylcholine esterase, purine catabolizing
enzymes , proteolytic enzymes, membrane stabilizing enzymes, respiratory enzymes, microsomal enzymes
etc. has been well recognized as evidenced by his research publications. Further, his research on developing
herbal medicines has been found very useful in prevention and treatment of chronic diseases and other
refractory diseases for which modern system of medicine have no permanent cure. He has worked on the
position of Joint Director, Council of Science & Technology, U.P., Lucknow, Department of Science &
Technology, Uttar Pradesh Government, India from the year 1979 to 2011, where he successfully executed
several R & D projects in various disciplines of Science &Technology including chemical & pharmaceutical
sciences, medical sciences, biological sciences, environmental sciences etc. During his tenure as Joint
Director, he has been instrumental in launching and implementing important schemes: Young Scientists
Scheme,Young Scientist Visiting Fellowship Scheme, Establishment of Centre of Excellence- Encephalitis
Research Centre of Excellence in Sanjay Gandhi Post Graduate Institute of Medical Sciences ( SGPGIMS),
Lucknow , U. P. India ; Centre of Excellence in Materials Science ( nano materials) in Z. H. College of Engg.
& Technology,Aligarh Muslim University,Aligarh, U.P. India, Establishment of Patent Information Centre
in the premises of Council of Science & Technology , U.P. He has also worked on the post of Secretary ( as
additional charge ) , Council of Science & Technology, U.P. several times and functioned asAdministrative
Head of the Organization. Prior to taking over the position of Joint Director, Council of Science &
Technology, U.P. in the year 1979, he has worked as Junior Research Fellow/ Senior Research Fellow
(Council of Scientific & Industrial Research, New Delhi ), Assistant Research Officer ( Jawaharlal Nehru
Laboratory of Molecular Biology) at Department of Pharmacology & Therapeutics, K.G. Medical College
(presently K. G. Medical University), Faculty of Medicine, University of Lucknow, Lucknow, India from
the year 1972 to 1979 and involved in multidisciplinary biomedical research leading to drug development .
He has worked as Visiting Scientist / Faculty in the Department of Physiology, School of Medicine,
University of North Dakota, Grand Forks, North Dakota, USA and also visited scientific institutions in
Sweden, U.K. and U.S.A. under Training Program on Capacity Building in Environmental Research
Management (World Bank Funding Project). After his superannuation in the year 2011, he has been
associated with International Institute of Herbal Medicine (IIHM), Lucknow, India as Professor and is
presently associated with Sky Institute, Lucknow, India as Director (Research) and Dean, Faculty of Science
& Technology, Sai Nath University, Jharkhand, India and involved in programs related to higher education
andresearchof scientific&technologicalfields. Hehas organizedseveralnationalandinternational
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conferences. He has actively participated in national and international conferences, symposia and
workshops and presented research papers and chaired scientific / technical sessions. He is life member and
fellow of many scientific societies such as National Academy of Sciences India, Society of Toxicology of
India, Indian Academy of Neurosciences, Bioved Research Society India, International Society for Herbal
Medicine (ISHM), Society of Biological Sciences and Rural Development, India. He has been member of
several scientific expert committees/ advisory committees to evaluate scientific research proposals. Dr.
Pandey has been actively associated with various universities and institutions in India as examiner for
conducting graduate, post graduate and doctoral level examinations in disciplines like chemical sciences,
pharmaceutical sciences, biochemical sciences, biotechnology and allied areas and member of Board of
Studies for the academic development in the department. He has been approved research supervisor for
guiding research in chemistry, biotechnology and related areas from various universities of India leading to
PhD Degree. In view of his vast research and administrative experience and broad R & D vision, Dr. Pandey
has been associated with International Journal of Scientific & Innovative Research (IJSIR) as Editor-in-
Chief.
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ADVANCED MICRO AND NANO DRUG DELIVERY SYSTEM 01 - 13
IN CANCER THERAPY
Pradeep Kumar, C.K. Dixit
ANTICANCER PLANTS: A REVIEW 14 - 19
*
V. Lakshmi, S.K.Agarwal and A.A.Mahdi
AGING IN INSECTS: AN OVERVIEW 20 - 27
Kalpana Singh
APPLICATION OF CARBON NANOTUBE AS A GAS SENSOR 28 - 31
Roshni Yadav and C.K.Dixit
AN OVERVIEW OF ANDROGRAPHIS PANICULATA 31 - 38
(BURM. F.) NEES
Vijai Lakshmi, Santosh Kumar Agarwal and Abbas Ali Mahdi
MOLECULAR DOCKING AND QSAR STUDIES OF 39 - 46
ANTIPSYCHOTIC RISPERIDONE DERIVATIVES AGAINST
SEROTON IN 5-HT RECEPTOR2A
* 1 2 1
Kiran Bhargava , Prahlad Kishore Seth , Kamlesh Kumar Pant , Rakesh Kumar
1 1
Dixit and RajendraNath
MOLECULAR DOCKING AND ADME/TOX STUDY OF 47 - 54
NIC LOSAMIDE DERIVATIVES AGAINST NS3 HELICASE OF JEV
Anjali Singh, Ajay Kumar, Vivek Srivastava
EFFECT OF PLANT EXTRACTS ON MOSQUITO 55 - 62
POPULATION
K. Singh and S. Nandan
FORMULATION AND EVALUATION OF POLYHERBAL 63 - 68
OINTMENT
Swapnil Dukare, Prajkta Gaikwad, Kolhe Shilpa Savata, S.L. Jadhav
COMPARATIVE STUDY ON MATCHING CRITERION 69 - 72
AND MOTION ESTIMATION OF ARRIVAL WAVES
Mohit Bajpai
IMPOTENCE OF COMPETENCY MAPPING 73 - 78
INTO KNOWLEDGE MANAGEMENT
Pushpendra Dixit
CONTROLANALOGUE ARRIVAL DATA USING 79 - 82
DIGITAL VISUAL INFORMATION
Mohit Bajpai
SECURITY FOR DEVELOPMENT OF 83 - 90
GPS EDUCATIONAL SYSTEM
Madhulata Nirmal
METHOD OF CHILDS LEARNING USING 91 - 94
CARTOONS AND NASQL
Madhulata Nirmal
STEADY STATE THERMALANALYSIS OF DISC 95 - 103
BRAKE ROTOR GRAY CAST IRON F12801
1 2
Hredey Mishra , Vikas Mishra
CONTENTS
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TRANSIENT THERMALANALYSIS OF DISC BRAKE 104 - 112
ROTOR GRAY CAST IRON F12801
1 2
Hredey Mishra , Vikas Mishra
THE EFFECT OF EXERTION ON HEART RATE AND RATING 113 - 116
OF PERCEIVED EXERTION IN INDOLENT FEMALES
1 1 2 1,3
Aisha Ansari , Mohammad Shahid Ali , Jagatheesan Alagesan , *Prathap S
EFFECT OF A SHORT BOUT OF EXERCISE ON CARDIORESPIRATORY 117 - 121
CHANGES IN IDEAL WEIGHT POPULATION
1 1 2 1,3
Mohammad Shahid Ali , Aisha Ansari , Jagatheesan Alagesan , *Prathap S
CONTENTS
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ADVANCED MICRO AND NANO DRUG DELIVERY SYSTEM
IN CANCER THERAPY
*Pradeep Kumar, C.K. Dixit
Radiation physics Laboratory, Dr. Shakuntala Misra National Rehabilitation
University, Lucknow, Uttar Pradesh, India
Address for correspondence: Pradeep Kumar, Radiation physics Laboratory, Dr.Shakuntala Misra
National Rehabilitation University Lucknow, Uttar Pradesh, India;
Email ID: pk_phyphd2016@dsmnru.ac.in
ABSTRACT
The diagnosis of cancer is more affected if the delivery of any drug at the right time and in the target
where it is needed and it is also necessary to known the required level of drug to appreciate the full
potential of therapeutic molecules. These requirementsare already more important inthe case of cancer
chemotherapies due to their high toxicity which could lead to serious side effects. Polymer conjugation is
also a drug delivery system in the diagnosis of cancer as well as nano and micro delivery system. Both
these methods are very important to diagnosis of cancer and improved the drug administrationand the
efficiency and safety of conventional chemotherapies. It also revolutionized in the pharmaceutical
andbiomedical industries in cancer therapy. In this review paper we have introduced the developments in
nanotechnology which offer researchers opportunities to significantly transform cancer therapies. This
technology has enabled the manipulation of the biological and physicochemical competence of
nanoparticles to facilitate more efficient drug targeting and delivery.This technology provides a better
resultthantraditionalmethodinthetreatmentofcancer.
Keywords:Cancer; Nanotechnology; Chemotherapy; Microand Nano particles;Treatment of Cancer by
Therapymethod
After more than a decennary of research and
development, micro and nanotechnology has
reshaped the tradition thinking of using material
[1]
for drug delivery in micro and nano range. Nano
and microscale molecules are smaller than human
cells by 100 to 10,000 times but are similar in size
to large biomolecules such as enzymes and
receptors. Nano and microscale devices are very
smaller size due to this these can easily enter most
cells, and those smaller than 20 nm can move out
of blood vessels as they broadcast by all the body.
Nano and microdevices are applicable to serve as
customized, targeted drug delivery vehicles to
carry large doses of chemotherapeutic agents or
therapeutic genes into malignant cells while
sparing healthy cells means that micro and nano
drug delivery are now showing much promise for
[1]
numerousdrug deliveryapplication.
Typically, micro and nanotechnology is
dened as the use of material and system whose
structures and components exhibit novel and
signicantly change properties when control is
[1]
gained at the micro and nano scale. The
advanced development of drug delivery has
improved therapeutic and toxicological
properties of existing chemotherapies and
[3]
facilitated the implementation of new one. By
including the drug in technologically optimized
drug delivery system or conjugating the drug with
different polymers, it is possible to modify the
pharmacokinetics and bio-distribution of the
drugs, improving the efcacy and security of the
[3]
therapy.
In cancer treatment, micro and nano
particles can further rely on the enhanced
permeability and retention effect caused by leaky
tumor for better drug accumulation at tumor sites.
These benets have made therapeutic nano-
particles a promising condition to replace
tradition chemotherapy, where intravenous
injection of toxic poses a serious threat to healthy
[1]
tissueandresultindose limitingsideeffect.
INTRODUCTION
1
International Journal of Scientific and Innovative Research 2017; 5(2) : 1 ‐ 13
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Table 1:
Late 1970 Current Future
First nanoscale drug delivery
system was lipid vesicles
Nowdays, liposome, cream,
capsule, tablets, gel, aqueous
solution, aerosols/spary
delivery are used as form of
delivery.
Nano and micro enabled
technology will take the
maximum share of the market
up nearly 90% of drug
delivery market.
Consider impossible to
administer the pharmaceutical
suspensions by intravenous
means due to abvious risks of
embolism.
15% of market uses
nanoparticles for drug delivery
system.
Safe, effective and without
side effect. No wastages and
increased bioavailabidity are
going to be basis of future
drug delivery.
CANCER
Cancers are abnormal cells which are different
from healthy cells because these cells divide more
rapidly than healthy cells. These cells found in
collective behavior. Due to this behavior they
form a mass of tissues is called a tumor. These
cancerous cells that come in excess amount cause
many problems to the bodies of patients. Figure-1,
which shows below, shows the difference
betweennormalandabnormalcell.
[Source- normal cell vs. bludder cancer cell ENCOGENCOGNITIVE
COM- 254*148-SEARCH BY IMAGE]Fig-1
GENETIC OF CANCER
Before we know fully main issue of this report
which deals with application of nanotechnology
in cancer prevention, detection and treatment, we
must indicate the underlying causes and the
genetic mechanisms involved in cancer. Here we
present an over-simplied text of what is known
[4]
on thegeneticofcancerfor sakeof brevity.
Cancer or neoplasm, on the other hand,
aggregate tissues composed of cells that divide
and grow abnormally. The intact number of
geneticchanges required for these malfunctions
remains unresolved for any cancer, but for adult
cancers believed to range from 5 to 15 nano -
[5]
meter. The division of the abnormal cell is
continues, and formed a large collection of cell.
This type cluster of abnormal cells is known as a
malignant tumour, and can furiously damage the
surrounding tissue as it sucks up essential
[6]
nutrients and displaces healthy cells. Eventually,
when the quantity of tumor is very large, then it
creates more problems in the bloodstream and
forming tumors in the other parts of body. This
latestphenomenonis known as metastasis.
2
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Effectively, it multiplies the cancer as well as its
effects and eventually will prove fatal to the
patient. In the below gure-2 and gure-3, show
that how generate abnormal cell in our body and
takeapartoftumorwhichiscalledcancer.
[Source-CANCER CELL CANCER RESEARCH UK Cancer research UK 375*263-search by image]
Fig-2
[Source-CANCER CELL CANCER RESEARCH UKCancer research UK 375*263-search by image]
Fig -3
CHEMOTHERAPY
Chemotherapy is a type of treatment for cancer. It
uses special drugs to kill cancer cell in body.
Chemotherapeutic proxy work by destroying
rapidly dividing cells, which is the main property
[17]
of neoplastic cells. Chemotherapy usually
assigns to the use of medicines or drugs to
treatment of cancer. The goal of chemotherapy is
[8,
to stop or slow the growth of cancer cells.
9]
Chemo drugs target rapidly growing cancer cell,
but they can also affect healthy cells that grow
rapidly. To remove this problem a new method is
created and is called radiation therapy. In this
treatment drug is not used to treat a cancer. It gives
abetterresultincomparisontoothertreatment.
Ordinarily, chemotherapy (chemo) hand
over to the use of medicines or drugs to treat
cancer. Therefore chemotherapy have important
role in treatment of cancer. But knowing what
chemotherapy is, how it works, and what to
expect can often help calm your fears. It can also
give you a better sense of control over your cancer
[10]
treatment.
1. How is Chemotherapy Used to Treat
Cancer?
Chemotherapy is most impotent method
for drug in treatment of any disease.
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Chemotherapeutic agents work by destroying
rapidly dividing cells, which is the main property
of neoplastic cells. But mostly people think that
chemotherapy is used for drugs in cancer
[17]
treatment.It's oftenshortenedto“chemo.”
Surgery and radiation therapy are also
treatment methodsfor cancer, remove and kill, or
damage cancer cells in a certain area, but chemo
can work throughout the whole body. This means
chemotherapy can kill cancerous cells that have
elaboration (metastasized) to parts of the body far
awayfromtheoriginal(primary)tumor.
2.Goalsof chemotherapytreatment
The main goals for chemotherapy (chemo) in
cancer treatment are three types which are
following:
1. Cure
2. Control
3. Palliation
2.1.Cure
Normally chemotherapy destroyed the cancerous
cell – it goes away and doesn't come back. But
tradition method doesn't promiseto prevention,
diagnosis and treatment of cancer therefore
many doctors don't use the word “cure” except as
a possibility or intention. So, when giving
treatment that has a chance of remedying a
person's cancer, the doctor may describe it as
treatment with curative occasion.There are no
guarantees, and though cure may be the goal, it
doesn't always work out that way. It often takes
many years to know if a person's cancer is really
cured.
2.2.Control
When the treatment (cure) of cancer is not
possible then the goal may be to control the
disease. Chemo is used to shrink tumors and/or
stop growing and spreading of cancer cells.
Therefore it can help the person with cancer feel
betterandlivelonger.
2.3.Palliation
Chemotherapy can also be used torepel
symptoms caused by the abnormal cells indite.
Thisiscalledpalliativechemotherapyorpalliation.
When cancer is in the last stage ie advanced stage,
meaning that it is not under control and abnormal
cells has spread from where it started to other parts
of the body. In this condition the goal may be to
improve the quality of life or help the person feel
better. For instanter, chemo may be used to help
shrink atumorthat'scausingpainor pressure.
3.Limitationsofconventionalchemotherapies
Chemotherapy is one of the main important
method for treatment of cancer but it has high
toxicity due to this it has some drawback, which is
proved harmful on the human body of cancer
patients, which could lead to serious side
effects,reducing the administrable and the
therapeutic effect and the main drawback of
conventional chemotherapy is that healthy cell are
also affected because it cannot give selective
[18,19]
actiononlytothecancerouscells.
Traditional chemotherapeutic agents often get
washed out from the circulation being devoured
by macro and nano phase. Cancerous cell are not
totally effective by chemotherapy because the
circulation of chemotherapeutic agents for a very
short time and cannot interact with the cancerous
cells. The major drawback behind the failure of
traditional chemotherapy is the poor solubility of
[20]
the drugs. Therefore the administered drugs
remain unsuccessful or cannot bring the desired
[21–22]
output.
In this review paper weare addressingthat the
treatment of cancerous cell is possible by nano
and micro drug delivery in chemotherapy which is
more effectively than traditional chemotherapy.
To improve the output for treatment of cancer it is
essential to transport the therapeutically active
molecule mainly to the target where it is needed
[10]
and at therequired time and level. This could be
achieved by embedding the drugs into nontoxic
and biodegradable polymers from which the drug
[11]
willbereleasedinasustainedmanner.
RADITIONTHERAPY
One of the most common treatments for cancer is
Radiation therapy. It uses high-energy particles or
waves, such as x-rays, gamma rays, electron
beams, or protons, to destroy or damage cancer
cells. Other names for radiation therapy are
[28]
radiotherapy,irradiation,orx-raytherapy.
Radiation can be used or used with other
treatments, such as surgery or chemotherapy. In
fact, denite drugs are known to be radio
sensitizers (RAY-dee-oh-SENS-it-tie-zers). This
means they can actually make the cancer cells
more sensitive to radiation, which helps the
[28]
radiationtobetterkillcancercells.
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MICRO AND NANO - TECHNOLOGIES
The dreadful opportunities exist for using micro
and nanoparticles as controlled drug delivery
systems for cancer treatment.[32]The term
“microparticle” refers to a particle with a diameter
of 1- 1000 mm, while “nanopaticle” is used when
the particle is <1 mm in size. However, under this
term it is possible to distinguish several reservoirs
including micro/nanocapsules, micro/nano
spheres, liposomes, etc. All these devices differ
not only in the structure (Figure 5) but also in their
biopharmaceutical cretic and therapeutic uses .
[33]The manufacturing protocol of each molecule
differs also considerably and the scale-up could be
a challenge for some of these devices. An
important issue to be considered when
manufacturing these systems is the drug load that
the reservoir can carry. This drug load depends on
the size and the structure of the device, ranging
fromsomefewmoleculesofthedrug toafew
5
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Examples of different drug delivery approaches that are FDA-approved or are in clinical development
as anti cancer treatments. Reproduced from Moses et al, 2003 with kind permission from Cancer Cell.
Figure 4

tens. Therefore, selection of drugs with potent
pharmaceutical activity is necessary in order to
have therapeutic effects in the released dose.
Furthermore, it is essential that the drug will not
be altered during the fabrication process and the
storage. Finally, interactions between drug and
the reservoir must be optimized to facilitate drug
release only in the target where it is needed and at
the desired kinetic-release. Natural and synthetic
polymers including albumin, brinogen, alginate,
chitosan and collagen have been used for the
structure of micro and nanoparticles. However,
among all of them, lactic-glycolic acid
copolymers are the most frequently employed
materials due to their biocompatibility and
biodegradability. Following a multiple emulsion
process, a drug can be entrapped into a poly
(lactic-co-glycolic) (PLGA) microsphere and
released at a zero-order kinetic by diffusion of the
drug through the polymer reservoir and the slow
degradation of the polymer matrix. These
advantages resulted in the rst two PLGA
microparticle extended-release formulations that
were approved by the US Food and Drug
Administration (FDA). One of themreleased the
]
recombinant humangrowth hormone (rhGH)
whereas the other microparticle-based drug
delivery system released the euteinizing-
hormone-releasing hormone (LHRH) agonist
[34]
leuprorelin acetate. The latter is currently on the
market under the name of Lupron® Depot and it is
approved in the United States for the palliative
treatment of advanced prostate cancer. However,
there are still few microencapsulated structure on
clinical trials addressing cancer treatments. In
fact, a recent review of National Cencer Institute
revealed that from the 1200 open clinical trials in
the United States only one to be testing a
microparticulate system for controlled drug
[35]
delivery. Experts, however, predict that within
the next 5-10 years some of the structure currently
understudy might progress to the clinical
evaluation and perhaps become marketed therapy
[36]
notso far.
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Although the total drug-load is reduced con-
siderably and the manufacture process is more
complex, the nano-scale devices present some
advantages over the micro-systems. In fact,
submicron systems show higher intracellular
uptake than microsized particles, thereby
allowing drug-release in different cellular com-
partments such as cytoplasm and nucleus. Nano-
particles can be also easily conjugated with a
ligand to favour a targeted therapeutic approach
and as it has been reported, some nanoparticles
can cross the blood-brain barrier (BBB). For
example, doxorubicin bound to polysorbate-
coated nano-particles can cross the intact BBB,
reaching therapeutic concentrations in the brain.
When these particles were administered in
gliobla-stoma-bearing rats, a very aggressive
human cancer with short survival times,
signicantly higher survival times were observed
in the treated animal group compared with all
[37]
other groups. Depending on the elaboration
method and the materials employed different
nanosystems can be distinguished including
micelles, nano-capsules, dendrimers, nano-
spheres, solid lipid nano particles and ceramic
nano-particles. The principal characteristics and
some of the recent research using eachnano-
systems isreviewedinTable2.
7
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Schematics of different nano technology based drug delivery systems for cancer therapy. Reproduced
from Sahoo and Labhas et.war, 2003 with kind permission from Drug Discovery Today. Figure 5:

Nano-technology can be used for more efcient
drug delivery system to tumor. Nano-particles can
control the basic functions of cells, and
potentially kill cancer cells, by virtue of their size
alone without the need for drugs. One of the
important mission of passive lipo-somal drug
delivery is to cancer. Lipo-somes are one of the
most well-known drug delivery carriers
employed in the treatment of cancer. Due to their
advantages, lipo-somal formulations provide a
substantial increase in anti-tumor efcacy
comparing with the free drug or standard
[38]
chemotherapy regimens. Liposomes are
composed of a double lipid bilayer which
encloses an aqueous space that can be employed
totransportanticancerdrugs.
The shape of liposome is a spherical vesicle
having at least one lipid bilayer. Liposome can be
used as a administration of nutrients and
pharmaceutical drug. Liposomes are nano-
particles ranging from 20 nm to 500 um in
diameter. They are small spheres, the wall that
separates the internal media from the external
environment is a lipid bilayer. Given that they are
comprised of both a lipid fraction and an aqueous
fraction, liposomes can incorporate lipophilic
[30]
substances and hydrophilic substances. Figure
6 schematically shows liposomes with the two
typesofload.
Nanotechnology can be used for more efcient
drug delivery system to tumor. Nanoparticles can
control the basic functions of cells, and
potentially kill cancer cells, by virtue of their size
alone without the need for drugs. One of the
important mission of passive liposomal drug
delivery is to cancer. Lipo-somes are one of the
most well-known drug delivery carriers
employed in the treatment of cancer. Due to their
advantages, lipo-somal formulations provide a
substantial increase in anti-tumor efcacy
comparing with the free drug or standard
[39]
chemotherapyregimens. Liposomesare
Nanoparticle Description Recent applications Reference
Nanocapsules Vesicular systems in which
the drug issurrounded by a
polymeric membrane
Stability of the cisplatin
nanocapsules has
been optimized by varying
the lipidcomposition of the
bilayer coat
Velinova et
al. 2004 [39]
Nanospheres Matrix systems in which the
drug is physically and
uniformly dispersed
Bovine serum albumin
nanospheres containing 5
uorouracil show higher
tumourinhibition than the
free drug
Santhi, et
al. 2002 [4 0]
Micelles Amphiphilic block
copolymers that canself -
associate in aqueous so lution
Micelle delivery of
doxorubicin
increasescytotoxicity to
prostate carcinoma cells
McNaealy, et
al. 2004 [41]
Ceramic
nanoparticles
Nanoparticles fabricated
using inorganiccompounds
including silica, titania…
Ultra ne silica based
nanoparticles releasingwater
insoluble anticancer drug
Roy, et al.
2003
[42]
Liposomes Articial spherical vesicles
producedfrom natural
phospholipids andcholesterol
Radiation -guided drug
delivery of liposomal
cisplatin to tumor blood
vessels results inimproved
tumour g rowth delay
Geng, et
al. 2004 [43]
Dendrimers Macromolecular compound
thatcomprise a series of
branches around aninner core
Targeted delivery within
dendrimers improved
the cytotoxic response of the
cells tomethotrexate 100 -fold
over free drug
Quintana, et
al. 2002 [44]
SLN particles Nanoparticles made from
solid lipids
SLN powder formulation of
all -trans retinoicacid may
have potential in
cancerchemoprevention and
therapeutics.
Soo -Jeong, et
al. 2004 [45]
Table 2: Examples of different nanoparticles and their applications as cancer treatments
8
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Liposome molecules are easily diffused into the
cells, since their structures and cell membrane
structure can interact very well while drug uptake
process. The enhanced permeation and retention
(EPR) effect is the concept that liposomes remain
in the bloodstream for a long time and are
collected passively from tumor cell. Through the
EPR effect, concomitant in toxicity problem of
therapy is relatively solved as lower and repeated
dose of liposome drug. The uses of EPR effect
allow up to 10 times the amount of drug to be
delivered to the tumor than the free drug
[31]
method. The characterization of liposome
moleculeis giveing.7
composed of a double lipid bilayer which
encloses an aqueous space that can be employed
to transport anticancer drugs.The shape of
liposome is a spherical vesicle having at least one
lipid bilayer. Liposome can be used as a
administration of nutrients and pharmaceutical
drug. Liposomes are nanoparticles ranging from
20 nm to 500 um in diameter. They are small
spheres, the wall that separates the internal media
from the external environment is a lipid bilayer.
Given that they are comprised of both a lipid
fraction and an aqueous fraction, liposomes can
incorporate lipophilic substances and hydrophilic
[30]
substances. Figure 6 schematically shows
liposomeswiththetwotypesof load.
Source- liposomes as as potential drug carrier system Intech-760*456-search by image ]
39
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[Source-http://www.lipomize.com/en/liposome] Figure6

In the below gure no 8, we are addressing the
process of working of nanoparticle drug delivery
to target the tumor and the way how can remove
thetumorandcontrolledtheabnormalcell.
[Source-http://pubs.acs.org/doi/abs/10.1021/nn900002m]
Figure 8
10
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CONCLUSION
Buy reviewing of this article, it is clear that
“nanotechnology is the key word of human life.”
Every eld is affected by the nanotechnology.
Nanotechnology changes the denition of many
object and has already revolutionized cancer
therapy in many aspects and is radically changing
the treatment pattern. Nanotechnology gives a
better result in the treatment of cancer.Nowadays
the treatment of cancer is very easily available in
comparison to past time. The treatment of cancer
by traditional method is very harmful for patient,
but by nano and micro drug delivery in therapy, it
is harmless. There are more advantages in the
treatment of cancer. The present paper reviews
the use of micro and nanotechnology as well as
macromolecular conjugation as strategies to
deliver existing chemotherapies and novel
therapeutic molecules in a controlled manner to
malignancies. These technologies come along
with other exciting drug delivery approaches such
as patches, microchips and osmotic pumps. In
general, the technologies described here improve
signicantly the pharmacokinetics and bio-
distribution of the free drugs and reduce
considerablytheirside-effects.
REFERENCES
1. Lei yang, Brain W.shaldon and Thonson J.
Webstet, “nanophase ceramic for improved
drug delivery”
2. Vinod Prabhu, Siddik Uzzaman,Viswanathan
Mariamal Berlin Grace, Chandrasekharan
Guruvayoorappan “nanoparticles in drug
delivery and cancer therapy : the giant rats
tail.
3. Moses MA, Brem H, Langer R (2003a) Novel
delivery systems in cancer chemotherapy.
Science&Medicine9,264-273.
4. G.Ali Mansoori , Pirooz Mohazzabi, Percival
Mc Cormack,Siavash Jabbari (2007)
technology and sustainable development, vol.
4,nos. 2/3,
5. Souhami, R.L., Tannok, I., Hohernberger, P.
and Horiot, J-C.(2004) Oxford textbook of
Oncology, 2002; Benjamin Lewin, Genes
VIII, Prentice-hall,p.889
6. Sadoqi M, kumar S, Lau-cam, Saxena V
(2016) Biocompatible nano-paticulates syste
for tumor diagnosis and therapy. In kumar
CSSR (Ed) Biological and pharmaceutical
nanomaterials.John wiely&Sons.
7. Omid C. Farokhzed and Robert Langer
“Laboratory of Nanomedicine and
Biomaterials and Department of Anesthes-
iology, Brigham and Women's Hospital and
Harvard Medical School, Boston, Massa-
chusetts 02115”,“MIT−Harvard Center for
CancerNano-technologyExcellence”.
8. www.chemotherapy.com/new_to_chemo/
what_is_chemo/
9. Zucchetti M, Boiardi A, Silvani A, Parisi I,
Piccol-rovazzi S, D' Incalci M(1999)
“distribution of daunoru-bicin and daunoru-
bicinol in human glioma tumor after
administrationof liposomedaunorubicin.
11
P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971
www.ijsir.co.in

Cancer ChemotherPharmacol44,178-179”
10. https://www.cancer.org/treatment/treatments-
and-side-effects/treatment-types/
chemotherapy.html
11. Orive G, Hernández RM, Gascón AR,
Calaore R, ChangTMS, DeVos P, Hortelano
G, Hunkeler D, Lacík I, ShapiroAMJ, Pedraz
JL (2003c) “Cell encapsulation: promise and
progress”. NatMed9,104-107.
12. Duncan R (2003) “ The dawning era of
polymer therapeutics”. Nat Rev Drug Discov
2,347-360.
13. Theodolou M, Clifford H (2004) “Cardiac
proles of liposomal anthracyclines: greater
cardiac safety versus conventional
doxorubicin? Cancer” 100,2052-2063.
14. Maeda H, Wu J, Sawa T, Matsumura K, Hori
K (2000) “ Tumor vascular permeability and
the EPR effect in macromolecular
therapeutics: a review” J Control Rel 65,
271-284.
15. Jain, RK (2001) “Normalizing tumor
vasculature with antiangiogenic therapy: a
new paradigm for combination therapy”. Nat
Med7,987-989.
16. Northfelt DW, Martin FJ, Working P,
Volberding PA, Russell J, Newman M,
Amantea MA, Kaplan LD (1996)”
Doxorubicin encapsulated in liposomes
containing surface-bound polyethylene
g l y c o l : P h a r m a c o k i n e t i c s , t u m o r
localization, and safety in patients with
AIDS-related Kaposi's sarcoma.” JClin
Pharmacol36, 55-63.
17. G. Zhao and B. L. Rodriguez, “Molecular
targeting of liposomal nanoparticlesto tumor
microenvironment,” International Journal of
Nanomedicine, vol. 8, pp. 61–71, 2013.
View at Google Scholar
18. K. T. Nguyen, “Targeted nanoparticles for
cancer therapy: promises and challenges,”
Journal of Nanomedicine & Nanotechnology,
vol. 2, no. 5, article 103e, 2011. View at
Publisher·ViewatGoogleScholar
19. A. Coates, S. Abraham, and S. B. Kaye, “On
the receiving end—patient perception of the
side-effects of cancer chemotherapy,”
European Journal of Cancer and Clinical
Oncology, vol. 19, no. 2, pp. 203–208, 1983.
ViewatGoogleScholar·ViewatScopus:
20. S.A. Mousa and D. J. Bharali, “Nano-
technology-based detection and targeted
therapy in cancer: nano-bio paradigms and
applications,” Cancers, vol. 3, no. 3, pp.
2888–2903, 2011. View at Publisher · View at
GoogleScholar·ViewatScopus
21. R. Krishna and L. D. Mayer, “Multidrug
resistance (MDR) in cancerMechanisms,
reversal using modulators of MDR and the
role of MDR modulators in inuencing the
pharmacokinetics of anticancer drugs,”
European Journal of Pharmaceutical
Sciences, vol. 11, no. 4, pp. 265–283, 2000.
ViewatPublisher·ViewatGoogleScholar·
22. View at ScopusM. E. Davis, Z. Chen, and D.
M. Shin, “Nanoparticle therapeutics: an
emerging treatment modality for cancer,”
Nature Reviews Drug Discovery, vol. 7, no. 9,
pp. 771–782, 2008. View at Publisher · View
atGoogleScholar·ViewatScopus
23. Levy Y, Hersheld MS, Fernandez C, Polmar
SH, Scudiery D, Berger M, Sorensen, RU
(1988) Adenosine deaminase deciency with
late onset or recurrent infections: response to
treatment with polyethylene glycol modied
adenosinedeaminase.J Pediatr113, 312-317.
24. Iakoubov L, Rokhlin O, Torchilin V (1995)
Antinuclear autoantibodies of the aged
reactive against the surface of tumor but not
normalcells.ImmunolLett47, 147-149.
25. Zhang Y, Guo L, Roeske RW, Antony AC,
Jayaram HN (2004) Pteroyl- -glutamate-
cysteine synthesis and its application in folate
receptor-mediated cancer cell targeting using
folatetethered liposomes.Anal Biochem 332,
168-177.
26. http://hcp.zoladex.net/Article/501611.aspx
27. http://www.clevelandclinic.org/myeloma
/pegasp.htm
28. https://www.cancer.org/treatment/
treatments-and-side-effects/treatment-
types/radiation/radiation-therapy-guide
/what-is-radiation-therapy.html
29. http://pubs.acs.org/doi/abs/10.1021/nn
900002m
30. http://www.lipomize.com/en/liposome
31. Sengupta S, Sasisekharan R (2007)
Exploiting nanotechnology to target cancer,
BrJ Cancer96:1315-1319
12
P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971
www.ijsir.co.in

32. Panyam J, Labhasetwar V (2003) Bio-
degradable nanoparticles for drug and gene
delivery to cells and tissue. Adv DrugDeliv
Rev55, 329-347.
33. Orive G, Hernández RM, Gascón AR,
Domínguez-Gil A, PedrazJL (2003b) New
approaches in the delivery ofbiophar
maceuticals.TrendsPharmSci25,382-387.
34. Cleland JL (1997) Recombinant human
growth hormonepoly (lactic-co-glycolic
acid) micro-sphere for-mulation
development. Adv Drug Deliv Rev 28, 71-
84.
35. Birnbaum DT, Brannon-Peppas L (2004)
Microparticle drugdelivery systems. In
Drug delivery systems in cancer therapy,Ed.
Brown DM, HumanaPress, 117-135.
36. Hedley ML, Curley JM, Langer RS (1998)
Microparticles for delivery of nucleic acid,
USA Patent 5783567, July 21; assigned to
PangaeaPharmaceuticals.
37. Steiniger SCJ, Kreuter J, Khalansky AS,
Skidan IN, Bobruskin AI, Smirnova ZS,
Severin SE, Uhl R, Kock M, Geiger KD,
Gelperina SE (2004) Chemotherapy in rats
with doxorubicinloaded nanoparticles. Int J
Cancer109, 759-767.
38. Drummond DC, Kirpotin D, Benz CC, Park
JW, Hong K (2004) Liposomal drug
delivery systems for cancer therapy In Drug
delivery systems in cancer therapy, Ed.
Brown DM, HumanaPress, 191-213.
39. Velinova MJ, Staffhorst RW, Mulder WJ,
DriesAS, Jansen BA, deKruijff B, deKroon
AI.Preparation and stability of lipid-coated
nanocapsules of cisplatin: anionic
phospholipid specicity.Biochim Biophys
Acta.2004 May27;1663(1-2):135-42.
40. Santhi K., Dhanaraj S. A., Joseph V.,
Ponnusankar S., Suresh B. A study on the
preparation and anti-tumor efcacy of
bovine serum albumin nanospheres
containing 5-uorouracil. Drug Dev. Ind.
Pharm. 2002;28:1171–1179. doi:
10.1081/DDC-120014584
41. McNealy TL, Trojan L, Knoll T, Alken P,
Michel MS. Micelle delivery of
doxorubicin increases cytotoxicity to
prostate carcinoma cells. Urol Res. 2004
Aug;32(4):255-60.Epub2004 Jan 9.
42. Indrajit Roy,Tymish Y. Ohulchanskyy,
HaridasE.Pudavar,EarlJ.
Bergey, Allan R. Oseroff, Janet Morgan,
Thomas J. Dougherty, and Paras N. Prasad
Ceramic-Based Nano-particles Entrapping
Water-Insoluble Photo-sensitizing Anti
cancer Drugs: A Novel Drug−Carrier
System for Photo-dynamic Therapy. J. Am.
Chem.Soc.,2003, 125 (26),pp7860–7865
43. Radiation-guided drug delivery of lipo-
somal cisplatin to tumor blood vessels
results in improved tumour growth delay.
Geng, 2004Nanotechnology Update Nano-
medicine– FightingCancer,
44. Quintana A, Raczka E, Piehler L, Lee I, Myc
A, Majoros I, Patri AK, Thomas T, Mulé J,
Baker JR Jr. Design and function of a
dendrimer-based therapeutic nano-device
targeted to tumor cells through the folate
receptor. Pharm Res. 2002 Sep;19(9):1310-
6.
45. Soo-Jeong Lim, Mi-Kyung Lee, Chong-
Kook Kim, Altered chemical and biological
activities of all-trans retinoic acid
incorporated in solid lipid nanoparticle
powders. DOI: 10.1016/j.jconrel.
2004.07.032
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ANTICANCER PLANTS: A REVIEW
*
V. Lakshmi, S.K.Agarwal and A.A.Mahdi
Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India
*Address for correspondence: Dr.Vijai Lakshmi, Emeritus Scientist, Department of Biochemistry,
King George's Medical University, Lucknow, U.P. , India
Email ID: vijlakshmius@yahoo.com
ABSTRACT
Over the last 4-5 decades, biologically active compounds derived from natural resources have
provided a number of useful cancer chemotherapeutic drugs. The search for natural products based drug
candidates is growing rapidly with the advancements in drug discovery and development techniques in
recent years, with the active fractions and isolates of marine organisms along with terrestrial plants and
microorganisms. The present review highlights the information about occurrence of such promising
leads from natural origin tend to create extensive interest among researchers including medicinal
chemists and pharmacologists working in anticancer drug research and therefore the availability of a
givenbriefinformationaboutcancerand anticancerdrug developmentfocusedon naturalproducts.
Keywords:Anticancer;MedicinalPlants.
Cancer is responsible for about 25% deaths
caused due to diseases in the developed countries
and is a major public health burden and challenge
for world health organization and research
[1-3]
organizations. It is considered as an adversary
of industrial revolution followed by advanced
pattern of socio-cultural life dominated by
excessive intake of exogenous chemicals and less
physical activities. The number of incidences of
different types of cancers is also increasing in
developing countries, as the extensive technical
advancements in the field of drug development
and other areas allowed their populations live
longer and make negative lifestyle changes
leading to increased risk of cancer. Cancer is a
broad group of diseases characterized primarily
by uncontrolled cell division leading to increase
in the number of malignant cells in a tissue,
invasion of adjacent tissues by malignant cells, or
spread of malignant cells through lymphatic or
circulatory system to regional lymph nodes and
distant tissues (metastasis). It develops through
multi-step process that initiates with small
preneoplastic changes, which may subsequently
[4,5]
progress to neoplasiab. Under certain
conditions, neoplastic cells escape the host's
immune surveillance that helps to develop the
capacity of growth, invasion and metastasis.
Cancer cells behave as independent cells and
proliferate continuously with out growth
regulation, leading to tumor development through
multi step process. An ideal anti cancer drug
would restore normal growth regulation and cell
cycle control to cancer cells through restoring
aberrant molecular signaling pathways and
inducing apoptosis in these cells. It should
selectively target different components of
physiological and biochemical pathways related
to different stages of cancer development without
affecting the normal cells. The discovery of new
compounds with novel mechanisms of action,
contribute to improved and highly effective
methodsfor cancertreatment.
A newer dimension in the anticancer drug
research is the increasing awareness about natural
products based chemotherapy. Several studies
have demonstrated that different plant-based
foods such as onion, grapes, garlic, ginger,
soybean, turmeric, cabbage, cauliflower, broccoli
and tomato can offer significant anticancer
potential. Natural products have provided four
importantcategoriesof antitumoragents:taxanes,
INTRODUCTION
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camptothecins, bisindole alkaloids also known as
vinca alkaloid and epipodophyllotoxins. Micro
organisms have also provided several potent anti
cancer drugs in form of anti cancer antibiotics
such as doxorubicin, actinomycin and mitomycin
C.
A natural product is a chemical compound or
substance produced by a plant, animal or
microorganism and usually has a pharma-
cological or biological activity which can be
utilized in pharmaceutical drug discovery and
drug design. Chemically natural products are
secondary metabolites, specifically produced by a
particular group of organisms and have been
postulated to play an important role in self defense
against predators as well as in interspecies
interactions. Their role is exceptionally pro-
nounced in the field of anti cancer drug research.
Roughly 50 % of the new chemical entities
introduced during last three decades were either
natural products or derived from natural products
through structural modifications. Due to
enormous advancement in the field of medicinal
chemistry, design of natural product or natural
product-mimetic scaffolds can be achieved
readily in one-step with the help of multi -
component reactions. Usually, natural products
are isolated only in minute amounts and thus
subsequent techniques are required to scale-up of
thebiologicallyactivemolecules.
With reference to above facts, the review has been
designed to cover the history of drug development
from natural resources, anticancer compounds
isolatedfromdifferentnaturalresources.
TYPES OFCANCER
Based on the histological characteristics hundreds
of different cancers have been identified, which
canbeclassifiedintosixmajorgroups.
1.Carcinomas
Cancers caused due to alteration in epithelial cells
covering the surface of skin and internal organs
are termed as carcinomas. It is the most common
type of cancers, predominantly occurring in the
old age, for example breast, prostate, lung,
pancreas, and colon cancers. Carcinomas,
account for 80 to 90 percent of all cancer cases.
These can be further divided into two major
subtypes: (i) Squamous cell carcinoma, which
develops in the squamous epithelium and (ii)
adenocarcinoma, which develops in an organ or
gland.
2.Sarcomas
Cancers arising on different connective tissue
including bone, cartilage and nervous system are
termed as sarcomas. These are known to develop
from cells originating in mesenchyma outside the
bone marrow. Most important examples of
sarcoma include fibro sarcoma (fibrous tissue),
rhabdomyosarcoma (skeletal muscle), angio-
sarcoma or heman gioendo the lioma (blood
vessels), glioma or astrocytoma (neurogenic
connective tissue found in the brain) mesothelial
sarcoma or mesothelioma (membranous lining of
body cavities)
3.Myelomas
These include the cancers arising in the bone
marrow plasma cells. These are also called
cancersof antibodyproducingwhitebloodcells
4.Lymphomas
These are developed in the lymph glands and
other organs of lymphatic system including
tonsils, thymus gland and spleen playing active
role in immune system. Lymphomas may also
occur in some other organs including breast,
stomach and brain. Lymphomas occurring in
these organs are known as extranodal
lymphomas.These can be further divided into two
major subtypes: (i) Hodgkin lymphomas and (ii)
non- Hodgkin lymphomas. Both of these subtypes
can be differentiated on the basis of the presence
ofreed-sternberg cellsinHodgkin lymphoma.
5.Leukemias
The cancers occurring in bone marrow are termed
as leukemia. It results in the overproduction of
immature white blood cells (WBC) rendering the
patients immunodeficient and susceptible to
subsequent infections.In some cases it also affects
red blood cells (RBC) and platelets leading to
anemia as well as defective blood clotting. The
important examples of leukemia include chronic
myelocytic leukemia (CML) occurring in adults,
acute myelocytic leukemia (AML) occurring in
children, chronic lymphocytic, lymphatic, or
lymphoblastic leukemia (CLL) common in
adults, acute lymphocytic, lymphatic, or
lymphoblastic leukemia (ALL) common in
childrenandadults.
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6.MixedTypes
These comprises of more than one component
which may be within one category or from
different categories. Examples of mixed type
include adenosquamous carcinoma, mixed
mesodermal tumor, carcinosarcoma and
teratocarcinoma.
NATURAL PRODUCTS AS SOURCE OF
THE RAPEUTIC AGENTS
The Mother Nature has been continuously serving
the mankind as most efficient arsenal, playing an
important role in health care and prevention of
diseases. Natural products have traditionally been
used in form of plant extracts, dry powders,
infusions, or other therapeutic preparations to
treat several diseases over centuries and continue
to play a highly significant role in the modern drug
discovery and development process providing a
diverse and unique source of medicinally active
molecules. Medicinal plants play a major role and
constitute the backbone of almost all the
traditional systems of medicine. Ayurveda,
known as the science of life is one of the oldest
system of medicines. This system of using natural
resources for betterment of health was originated
in India long ago in the pre-Vedic period through
day by day experiences and experimentations
with the aim of maintaining health and treatment
of various diseases. Several other systems of
complementary and alternative medicines
including Siddha and Unani are also developed
from plant based formulations through
experience and interactions with natural
resources. The earliest written evidence related to
use of plant products as therapeutic agents is
available on Atharvaveda, one of the four most
ancient books of knowledge and culture related to
Hindu religion showing the strength of Indian
wisdom. As many as 114 different therapeutic
formulations have been described for the
treatment of different diseases. The therapeutic
importance of Indian medicinal plants has been
exposed thoroughly in the Susruta samhita and
Charaka samhita during the Vedic period. Indian
Materia medica has description of more than 2000
drugs derived from natural resources most of
which are originated from different systems of
traditional and folk practices. 80 % of these drugs
are of plant origin whereas the rest are minerals or
animal products.Indian medicinal plants possess
enormous therapeutic potential but only a small
proportion of it has been explored by mankind
leaving the great opportunity to discover novel
drugs from natural origin. Numerous therapeutic
preparations have been developed by traditional
healers and Ayurvedic practitioners for the
treatment of various disorders and diseases.
Subsequently after the emergence of natural
product chemistry thousands of new medicinal
plant were identified with immense therapeutic
potential. Natural Products chemistry together
with analytical chemistry, spectroscopy,
pharmacology, biochemistry and other related
disciplines demonstrated its value for drug
development. It has not only enriched modern
medicine with novel bio-active molecules but also
provided valuable leads for drug designing. Since
the isolation of morphine from Papaver somni-
ferum in 1806, extensive efforts are being done to
isolate therapeutically active molecules from
medicinal plants. Some important examples
include emetine, colchicine, atropine, cocaine,
ephedrineandquinidine.
BIOASSAY GUIDED DRUG DISCOVERY
Bioassay-directed fractionation supported by
several recent techniques is extensively used to
identify the active principles/pure compounds
present in crude natural products preparations.
This approach can be used systematically to
reduce the complexity of the extracts/fractions in
order to locate the biological activities of complex
materials. It resolves the complex mixtures to
[6,7]
more simple and pure form. Considering on
therapeutic preparation obtained from crude
extracts, only a specific portion of the extract-the
active principles/bioactive molecules with
specific biological targets is of interest. In view of
this fact, a bio-molecular interaction step should
be included into analytical methods to achieve
bio-selectivity and to purify the compounds with
specifictherapeuticactivity.
POTENTIALANTICANCER AGENTS
OBTAINED FROM NATURAL PRODUCTS
Citrus fruits and green vegetables provide a rich
source of vitamins, flavonoids and other
polyphenolic compounds, adequate consumption
oftheseplantproductsreducetheriskof cancer.
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More than 1,000 non-nutritive plant derived
compounds are known to have cancer-preventive
activity. More than 400 plant derived compounds
with anticancer potential are under investigation. .
Most of the species of higher plants,
microorganisms, arthropods, and marine
invertebrates are still not studied and thus these
diverse natural resources can be explored to
provide novel anticancer agents. Recent studies
have identiﬁed new species of bacteria, algae,
fungi, and vertebrates which are able to provide
new anticancer molecules. Some important
medicinal plants possessing anticancer potential
arelistedintable1.
Table 1: Some important Medicinal Plants possessing anticancer activity
Plant name Family Active
part
Plant name Family Active part
Acacia
xanthophloea
Leguminosae Fruit Ipomea batata Convolvulaceae Rhizome
Adenium obesum Apocyn aceae Leaf Juncus acutus Juncaceae Leaf
Adiantum
macrophyllum
Pteridaceae Entire Lannea
stuhlmannii
Anacardiaceae Root
Aeonium
arboretum
Crassulaceae Leaf Lavandula
angustifolia
Meliaceae Leaves
Aglaia foveolata Meliaceae Fruit Lep tadenia
hastate
Asclepiadaceae Bark
Alnus japonica Betulaceae Wood Ligustrum
lucidum
Oleaceae Seed
Aphanamixis
polystachya
Meliaceae Stem bark Maytenus
canariensis
Celastraceae Fruit juice
Arisaema
erubescens
Araceae Root Ma ytenus
macrocarpa
Celastraceae Stem bark
Aster amellus Compositae Entire Maytenus
serrata
Celastraceae Seed
Azadirachta
indica
Meliaceae Leaf Monnina
obtusifolia
Polygalaceae Aerial parts
Begonia glabra Begoniaceae Entire Morinda
ci trifolia
Rubiaceae Root
Carapa
guianensis
Meliaceae Seed oil Ocotea foetens Lauraceae Branchlets
Cassia
quinquangulata
Caesalpiniaceae Root Pinus
parviﬂora
Pinaceae Strobilus
Celastrus
orbiculatus
Celastraceae Entire Piper
latifoli um
Piperaceae Leaf
Crassocephalum
bojeri
Compositae Entire Plantago
asiatica
Plantaginaceae Leaf
Combretum
caffrum
Combretaceae Bark Pleione
bulbocodioides
Orchidaceae Tuber
Cyathea fauriei Cyatheaceae Shoot Pratia
nummularia
C ampanulaceae Entire
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Dillenia
suffruticosa
Dilleniaceae Fruit Phymatosorus
diversifolium
Polydiaceae Root
Dioscorea
collettii
Dioscoreaceae Rhizome Phytolacca
esculenta
Phytolaccaceae Root
Dysosma
pleiantha
Berberidaceae Root Rabdo sia
rubescens
Labiatae Leaf
Caragana
cuneata
Leguminosae Leaf Ruellia
tuberose
Acanthaceae Bark
Croton flavens Euphorbiacaeae Leaf Salvia
chinensis
Labiatae Entire
Croton lechleri Euphorbiacaeae Latex Salvia
officinalis
L abiatae Leaves
Cynanchum
hancoekianum
Asclepiadaceae Entire Scirpus
holoschoenus
Cyperaceae Inflorescence
Deeringia
amaranthoides
Amaranthaceae Fruit Scutellaria
barbata
Labiatae Entire
Echinops grijisii Compositae Root Scu tellaria
indica
Labiatae Root
Echinops
latifolius
Compositae Root Sempervivum
armenum
Crassulaceae Leaf
Echites
vucatanensis
Apocynaceae Latex Sempervivum
arvense
Crassulaceae Leaf
Epilobium
hirsutum
Onagraceae Entire Swiet enia
humilis
Meliaceae Seed
Euphorbia
ebracteolata
Euphorbiacaeae Aerial
parts
Tabebuia
impetiginosa
Bignoniaceae Stem bark
and wood
Euphorbia
heterophylla
Euphorbiacaea Stem Tabebuia
rosea
and wood
Euphorbia
marginata
Euphorbiacaeae Entire Tabebuia
serratifolia
and wood
Euphorbia
kansui
Euphorbiacaeae Root Thalictrum
fabri
Ranunculaceae Root
Euphorbia
prolifera
Euphorbiacaeae Latex Thevetia
ahouia
Apocynaceae Le af a nd
Stem
Ficus pretoiae Moraceae Sap Thevetia
gaumeri
Stem
Hedyotis
chrysotricha
Rubiaceae Entire Thevetia
peruciana
Stem
Hippophae
salicifolia
Elaeagnaceae Fruit Uncaria
tomentosa
Rubiaceae Bark
Hypoxis nyasica Hypoxiaceae Rhizome Virola
bicuhyba
Myristicaceae Seed
Hypoxis rooperii Hypoxiaceae Tuber Viscum album Loranthaceae Leaves
Inula
linariaefolia
Compositae Flowers Viscum
calcaratum
Loranthaceae Entire
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CONCLUSION
Research work done up to date has shown the
importance of medicinal plants in the field of
different human diseases including cancer,
intense efforts and multiple approaches have
fructifies in form of number of anti-cancer drugs
in the area but the main problem associated with
these drugs is the toxicity, solubility and lack of
specificity as healthy cells are also become the
target, most of the modern anti-cancer drugs
available are either inspired from natural product
or their analogues, efforts are still required to keep
the delicate balance between toxicity, bio-
availability and efficacy, drugs available are not
good enough to treat cancer at advance stage
though may prolong the life span of person, other
drawback is the cost of anti-cancer drugs which
must also be taken into account for the countries
like India, a lot need to be done and nature has
given the direction. More clinical trials are also
needed to validate the usefulness of these agents
either alone or in combination with existing
therapy.
ACKNOWLEDGMENTS
The authors are grateful to the Director CSIR-
CDRI, Lucknow, India for providing excellent
library facilities and UGC, Government of India,
New Delhi for providing financial support in the
formofEmeritusfellowshiptoVL.
REFERENCES
1. American Cancer Society. Cancer Facts and
Figures. American Cancer Society Inc 250
Williams Street, NW, Atlanta, GA. American
CancerSociety,2012.
2. Stewart BW, Kleihues P, editors World
Cancer Report (World Health Organization,
International Agency for Cancer Research),
IARC Press, Lyon, France,2003,p.11-20.
3. Golub TR, Slonim, DK, Tamayo P, Huard C,
Gaasenbeek M, Mesirov JP, Coller H, Loh
ML, Downing JR, Caligiuri MA, Bloomfield
CD, Lander ES. Molecular classification of
cancer: class discovery and class prediction
by gene expression monitoring. Science
1999;286:531-537.
4. Hakomori SI. Aberrant glycosylation in
cancer cell membranes as focused on
glycolipids: overview and perspectives',
CancerRes1985;45:2405–2417.
5. Ogata S, Muramatsu T, Kobata A. New
structural characteristic of the large
glycopeptides from transformed cells. Nature
1976;259:580–582.
6. Altenburger R, Backhaus T, Boedeker, W,
Faust M, Scholze M, Grimme LH. Pre-
dictability of the toxicity of multiple chemical
mixtures to Vibrio fischeri: Mixtures com-
posed of similarly acting chemicals. Environ
ToxicolChem2000;19:2341–2347.
7. Warne MSJ, Hawker DW. The number of
components in a mixture determines whether
synergistic and antagonistic or additive
toxicity predominate-The funnel hypothesis.
EcotoxicolEnvironSaf1995;31:23–28.
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AGING IN INSECTS: AN OVERVIEW
*Kalpana Singh
Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India
*Address for correspondence : Dr. Kalpana Singh, Assistant Professor, Department of Zoology,
University of Lucknow, Lucknow, Uttar Pradesh, India
Email ID: drkalpanasingh@gmail.com
ABSTRACT
Aging can be defined as a decline in rate of physiological repair, an increase in probability of death and a
decline in fertility with advancing adult age. It affects virtually all demographic, behavioral and
physiological parameters in an individual. Its effect on activity levels and reproductive behaviour such
as mate choice are well studied in insects. Reproductive attributes such as fecundity and egg viability are
affected by the age of mating pair; however effects of paternal age are less studied. Effects of maternal
age on offspring life span are well established in many animal groups (Lansing effect). Many theories
have been proposed to explain the causes and evolution of aging; viz. mutation accumulation hypothesis,
antagonistic pleiotropy hypothesis, disposable soma theory. Lansing effect may also play an important
roleinevolutionofagingemphasizing theimportanceofparentalageatthetimeofreproduction.
Keywords: Aging; Mate Choice; AternalAge; Paternal Age; Progeny Fitness
Aging is a function of time over biological
systems. It has fascinated the scientists the world
over since it affects each and every aspects of life.
It still remains a great mystery although
systematic efforts have been going on since last
century to understand it. It affects the life
[1,2,3]
attributes and physiology of organisms. All
over the biological world only a small percentage
of organisms survive in nature that are subjected
to age. The effects of aging are much more
pronounced in captive populations that live in
[4,5]
benign condition. Insects being a good model, a
lot of base line studies have been conducted on
[6]
them although there are numerous studies on
[7,8,9,10]
human beings and other mammals. Since,
life span of insects is very short so the genetics and
evolution of genetics had predominantly in-
[6]
vestigatedininsects.
Aging has been defined in many ways. As per
physiological definition it is a decline of state of
repair with increasing age. While actuarial
definition states it as an increase in mortality rates
of a population with increasing age. As per
evolutionary definition it is a persistent decline in
components of fitness (rates of survival and
[11]
reproduction)withincreasingage.
Thus, aging can comprehensively be defined as a
decline in fertility, a decline in rate of physi-
ological repair and an increase in probability of
[11]
death with advancing adult age. There are
numerous prolonged demographic studies that
report aging in the form of an increase in
probability of death and decline in fertility with
[12]
advancing adult age. Its rate may differ and
evolve in different organisms although it is
[13]
recognizedthatagingismaladaptive.
Keeping in view the universal presence of aging
this article aims to review the studies on aging,
aging theories, aging rates and aging effects on
lifeattributesininsects.
THEORIES OF AGING
Various theories have been put forward to explain
the phenomenon of aging and its causes and
evolutionary significance. These theories can be
summed up into two categories intrinsic
[14]
(programmed) and extrinsic (Stochastic). These
two types of theories interact also such as in
disposablesoma (extrinsic)theory.
There are many theories that may fall into
intrinsic theory category such as mutation
accumulationhypothesisandantagonistic
INTRODUCTION
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pleiotropic hypothesis. Mutation accumulation
hypothesis states that the aging is caused due to
the increase in mutation rates along with the
decreasing force of natural selection and this in
turn leads to less probability of survival at later
[3,15,16]
ages. This corroborates with the studies
conducted since 1940's where evolutionary
biologists have argued that the age related
decrease in the force of natural selection leads to
[17,2,3]
evolution of aging. According to antagonistic
pleiotropic hypothesis a new mutation that
increases fertility and fitness levels at young age
at the expense of lowered fitness levels later in life
[2,15,16]
(pleiotropiceffect)willbeselected.
Disposable soma theory of aging explains that
aging is an environmentally driven balance
between investment in reproduction and
[18]
maintenance of soma. It observes that (i)
somatic maintenance has a cost, (ii) maintenance
of the soma more than the natural expectation of
life is disadvantageous, and (iii) maximum deaths
in natural populations is due to extrinsic mortality.
This is a physiological ecology based life history
optimization theory that somewhere converges
with the antagonistic pleiotropy theory of
[19,18] [14]
aging. According to Heininger(2012) aging
is a deprivation syndrome driven by a germ soma
conflict. This helps to explain the multiple life
historytrade-offsoccurringinorganisms.
The studies conducted on Drosophila melan-
ogaster have substantiated the mutation and
[20,15,21,22]
antagonistic pleiotropy theories of aging.
Results of experiments conducted on D. melan-
[23,24,25]
ogaster about age specific genetic variance
[26]
& inbreeding depression have corroborated the
importance of mutation accumulation in aging.
However there are studies on artificial selection
experiments that enforce the importance of
pleiotropy. Gerontologists have shown great
[21,27]
interestinantagonisticpleiotropicstudies.
EFFECTS OF AGE ON LIFE TTRIBUTES
On ActivityLevels
Predator's age have been found to influence rate of
predation in ladybird beetle, C. transversalis and
C. sexmaculata. Rate of assimilation and speed of
locomotion were also found to decline with
[28]
increase in age that indicates senescence.
Almost all demographic, behavioral and
physiological parameters are known to quali-
[12,29]
tativelydeterioratewiththeincreaseinage.
Reproductive senescence in terms of decrease in
fecundity and exhaustion of reserves in adults has
been demonstrated in hymenopteran parasitoids,
[30] [31,32,33] [34]
lepidopterans &ladybirds.
OnMateChoice
There are many studies that investigate the role of
age in the choice of mates in insects.These studies
have come out with three various models that
explain the behavior of female exerting the age
based choice of mates. Few studies suggest that
females tend to choose old males as mates and this
formulates the good genes model or indicator
[35,36,37,38]
mechanism. This theory explains that older
males have proven their fitness by their long
[29,40]
survival thus should be selected. There are
[41,42,43,44,45,46,47]
many studies to substantiate the same.
This model suggests that that individuals differ in
genetic quality leading to increased survival and
fecundityof higherqualityindividualsatallages.
However there are some contrary reports.
[48,49,50,51,52]
Mate choice model put forward by
[53]
Hansen &Price (1995) presents that females
[54,55]
choose younger males as mates. They suggest
that a trade-off between early and late-life fitness
componentsis likelytoleadtosuchpreference.
The third model suggests that female choose
[56,57]
middleagedmates.
OnMatingIncidences
There are many studies that report the effect of
aging on mating incidences i.e. how many mating
does a insect undergoes at different ages. Age
specific mating incidences have been recorded in
Adaliabipunctata to analyze the phenomenon of
[58]
protandry and protogyny. The males started
mating after 4 days of age while female mated at
the age of 2 days in Coccinellaseptempunctata.
Age related decrease in willingness to mate and
decrease in mating incidences were found after
40-50 days of age in both the sexes of this
[59]
beetle. In pale morph of Propyleadissecta few
younger females have chosen the older males
while older females have chosen the older
[60]
males.
OnMaleReproductiveAttributes
There are very few studies on insects dealing with
effect of paternal (male) age on reproductive
fitness of its own or that of females. Studies in
ladybirdsconsideringtheassessmentofpaternal
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age effects on reproductive attributes came out
with significant results. Viability of eggs laid was
found to be male-age-dependent function. Up to
the age of 30 days there was no decline in percent
[ 60]
viability in pale morph of Propyleadissecta and
decline was observed after 30 days in
[59]
Coccinellaseptempunctata and Cheilomeness
[61]
exmaculatus.
The effects of male age and its effects are largely
ignored aspect of studies in insects. However Fox
[62]
et al., (1995) dealt with variation in ejaculate
sizewithageanditseffectonfemalefecundity.
OnFemaleReproductiveAttributes
Some lepidopterans exhibit a decline in egg
[63,
production with increasing age of mother.
64,65,66,67,68]
Decline in egg size with advancing
maternal age have been reported in butterflies that
[69,70,71,72]
lay their eggs singly. In braconid Micro
[73]
plitscroceipes (Cresson), chalcid, Brachy-meris
[74]
inter media (Nees) and Female moth Epi-
[75]
phyaspostvittana (Walker) showed decreasing
fecundityandfertilitywithincreasingage.
In ladybeetle, C. montrouzieri fecundity was
significantly affected by the age of female, as 5 to
15-day-old females laid larger number of
[76]
eggs. In ladybirds C. septempunctata and P.
dissecta(pale morph) fecundity was affected by
the advancing age of the females. Senescence was
reported after 20 days in females of both the
[60,59]
ladybirds.
In Drosophila melanogaster it was reported that
the last male sperm precedence declined
significantly in three strain of the species
indicating the start of senescence as physiological
[77]
deterioration.
EffectofAging on OffspringFitness
The younger mother, on the average, had the
longest lived offspring-Alexander Graham Bell
(1918) . Researchers have found that in insects
older mothers have shorter lived offspring in
[78] [79] [81]
house flies, fruit flies, stink bugs, flour
[82] [83,84]
beetles, and mealworms. This is referred to
as the Lansing effect,after Albert Lansing's
[85,86,87]
(1947,1948,1954) renowned work on
rotifers.
In C. montrouzieri the female age had non-
[76]
significant effect on development of grubs.
However in fruit flies it was reported that delayed
mating of mothers had affected the rate of
recombination and non-disjunction in their
[88]
offspring. In Brachymeriaintermedia (Nees)
[89]
maternalagecontrolsitspopulationgrowth.
[90]
Priest et al.,(2002) reported that age of mother
had affected the longevity of her offspring. In the
wild caught strain of D. melanogaster age of
mother had affected the male progeny life
expectancy. It was found that mothers which
reproduced continuously throughout their life
have offspring with higher life expectancy than
the mothers with delayed reproduction. The
results show that maternal age affects the patterns
ofagingofoffspring.
A single study in ladybirds demonstrates that the
age of parental generation affects the reproductive
parameters of progeny thus playing critical role in
[91]
determiningfitness of futuregenerations.
CAUSES AND EVOLUTION
[10]
Kirkwood (2002) explains aging with the
disposable soma theory that tells that aging is a
balance between investment in reproduction and
maintenance of soma which is also environ-
mentally modulated. Whereas, Heininger
[14]
(2012) has explained aging as a deprivation
syndromedrivenbyagermsomaconflict.
The Lansing effect predicts that the older mother
produce short lived offspring. This effectmay also
have asignificant role in the evolution of aging.
Natural selection may also operate on the
offspring produced by parents of different ages
thus influencing the evolution of aging provided
the effect of parental age on offspring longevity
variesamongdifferentgenotypes.
There are many studies that show that longevity
and survival of the organisms including insects
depends on their sexual activity in males and
reproductive efforts in terms of mating,
[92,93,94,95,96]
ovipositioninfemales.
Life history evolution for understanding the
mechanism of aging has been explained by
resource allocation models.This model postulates
that there is a trade-off between different life
history traits and reproduction is costly and often
[1,97,
results in either lowered fecundity or survival .
98,99,100,101]
This trade-off is well studied in
[20,94,102,27,103]
Arthropoda especially in insects.
Increasedreproductionis costlyas itmayleadto
22 www.ijsir.co.in
P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

reduced longevity. In female insects it is
[35,102]
expressed as purely phenotypic effects or as
[104]
additive genetical effects. It is very well
[92]
demonstratedinD. melanogaster.
ACKNOWLEDGEMENT
The author is grateful to the Head, Department of
Zoology, University of Lucknow, Lucknow, Uttar
Pradesh, India for providing necessary laboratory
facilities.
REFERENCES
1. Fisher, R.A. The Genetical Theory of Natural
Selection.Oxford:ClarendonPress. (1930).
2. Williams, G.C. Pleiotropy, natural selection
and the evolution of senescence. Evolution.
(1957);11:398-411.
3. Hamilton, W.D. The molding of senescence
by natural selection. Journal of Theoretical
Biology.(1966);12:12-45.
4. Ricklefs, R.E. Evolutionary theories of
aging: confirmation of a fundamental
prediction, with implications for the genetic
basis and evolution of life span. The
AmericanNaturalist.(1992);152:24-44.
5. Wachter, K.W. & Finch. C.E. Between Zeus
and the Salmon. The Biodemography of
Longevity.NationalAcademyPress. (1997).
6. Arnqvist, G. & Nilsson, T. The evolution of
polyandry: multiple mating & female fitness
in insects. Animal Behavior.(2000); 60: 145-
164.
7. Finch, Caleb E.; Tanzi, Rudolph E.Genetics
of Aging. Science. (1997); 278, (5337), p.
407 (1997).
8. Kirkwood, T.B.L. &Austad, S.N. Why do we
age.Nature.(2000);408:233-238.
9. Kirkwood, T.B.L. Human senescence.
BioEssays.(1996);18:1009-1016.
10. Kirkwood, T.B.L. Evolution of ageing.
Mechanisms ofAgeing Development.(2002);
123:737-745.
11. Mangel, M. Complex adaptive systems, aging
and longevity. Journal of Theoretical
Biology.(2001);213:559-571.
12. Finch, C.E. Longevity, Senescence and the
G e n o m e . U n i v e r s i t y o f C h i c a g o ,
Press.(1990); pp.922.
13. Medawar, P.B. An Unsolved Problem of
Biology.H. K. Lewis,London.(1952).
14. Heininger K. The Germ-soma Conflict
Theory of Aging and Death: Obituary to the
"Evolutionary Theories of Aging". Webmed
Central AGING (2012); 3(4):WMC003275
doi:10.9754/journal.wmc.2012.003275
15. Partridge, L. & Barton, N.H. Optimality,
mutation and the evolution of aging.
Nature.(1993);362:305-311.
16. Pletcher, S.D. and Curtsinger, J.W. Mortality
plateaus and the evolution of senescence:
why are old-age mortality rates so low?
Evolution.(1998); 52:454-464.
17. Medawar, P.B. Old age and natural death.
Mod. Q. (1946); 2:30-49.
18. Kirkwood T. B. L. and Rose, M. R. Evolution
of Senescence: Late Survival Sacrificed for
Reproduction. In, The Evolution of Repro-
ductiveStrategies(1991);pp. 15-24
19. Kirkwood, T. B. L. Evolution of ageing.
Nature,Lond.(1977);270, 301-304.
20. Rose, M. Laboratory evolution of postponed
senescence in Drosophila melanogaster.
Evolution.(1984);38:1004-1010.
21. Zwaan, B., Bijlsma, R. & Hoekstra, R.F.
Direct selection on life span in Drosophila
melanogaster. Evolution. (1995); 49: 649-
659.
22. Charlesworth, B. & Hughes, K.A. Age
specific inbreeding depression and compo-
nents of genetic variance in relation to the
evolution of senescence. Proceedings Natio-
nal Academy of Sciences, USA. (1996);
93:6140-6145.
23. Hughes, K.A. &Charlesworth, B. A genetic
analysis of senescence in Drosophila.
Nature.(1994);367:64-6611.
24. Promislow, D.E., Tatar, M., Khazaeli, A.A.
&Curtsinger, J.W. Age-specific patterns of
genetic variance in Drosophila melanogaster.
I.Mortality.Genetics.(1996); 143:839-848.
25. Tatar, M., Promislow, D.E.L., Khazaeli, A.A.
&Curtsinger, J.W. Age-specific patterns of
genetic variance in Drosophila melanogaster.
II. Fecundity and its genetic covariance with
age-specific mortality. Genetics. (1996); 143:
849-858.
26. Charlesworth, B. & Hughes, K.A. Age
specific inbreeding depression and compo-
nentsofgeneticvarianceinrelationto
...... 1
23www.ijsir.co.in
P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

the evolution of senescence. Proceedings
NationalAcademy of Sciences, USA. (1996);
93:6140-6145.
27. Partridge, L., Prowse, N. &Pignatelli, P.
Another set of responses and correlated
responses to selection on age at reproduction
in Drosophila melanogaster. Proceedings
Royal Society of London. Part B. Biological
Sciences.(1999);266:255-261.
28. Dixon AFG, Agarwala BK. Triangular
fecundity function and ageing in ladybird
beetles. Ecological Entomology. (2002);
27:433–440.
29. Rose, M. Evolutionary Biology of Aging.
Oxford University Press. Oxford, New
York.(1991).
30. Fernando, L.C.P. & Walter, G.H. Activity
patterns and oviposition rates of
Aphytislignanensisfemales, a parasitoid of
California red scale Aonidiellaaurantii
implications for successful biological control.
EcologicalEntomology.(1999);24:416-425.
31. Dunlap-Pianka, H., Boggs, C.L. & Gilbert,
L.E. Ovarian dynamics in Heliconiine
butterflies: programmed senescence versus
eternalyouth.Science.(1977);197:487-490.
32. Boggs, C.L. Reproductive strategies of
female butterflies: Variation in and constraints
on fecundity. Ecological Entomology. (1986);
11:7-15.
33. Boggs, C. L. Resource allocation in variable
environments: Comparing insects and plants.
(F. Bazzaz and J. Grace, Eds.) Plant Resource
Allocation.AcademicPress. (1997);73-92.
34. Blackman, R.L. The effects of different aphid
foods on Adaliabipunctata L. and Coccinella
septe-mpunctata L. Annals of Applied
Biology.(1967);59:207-219.
35. Trivers, R.L. Parental investment and sexual
selection. In: Sexual Selection and the
Descent of Man-1871-1971 (ed. B.
Campbell.) Chicago 1L:Aldine Press. (1972);
P.136-179.
36. Halliday, T.R. Sexual selection and mate
choice. In: Behavioral Ecology: An
Evolutionary Approach (eds. Krebs, J.R. &
Davies, N.B.). Blackwell Scientific
Publishers, London.(1978);P.180-213.
37. Halliday, T.R. The study of mate choice. In:
Mate choice (ed. P. Bateson). Cambridge
UniversityPress. Cambridge.(1983);P.3-32.
38. Manning, J.T. Choosy females and correlates
of male age. Journal of Theoretical
Biology.(1985);116:349-354.
39. Kokko, H. & Lindstrom, J. Evolution of
female preference for old mates. Proceedings
of the Royal Society of London, Series B.
(1996); 263:1533-1538.
40. Kokko, H. Good genes, old age and life-
history trade-offs. Evolutionary Ecology.
(1998);12:739-750.
41. Burley, N. Mate choice by multiple criteria in
a monogamous species. The American
Naturalist.(1981);117:515-526.
42. Grant, B.R. & Grant, D.P.R. Mate choice in
Darwin's finches. Biological Journal of the
LinneanSociety.(1987);32:247-270.
43. vanRhijn, J. &Groothius, T. On the
mechanism of mate selection in black-headed
gulls.Behaviour.(1987);100:134-169.
44. Conner, J. Older males have higher
insemination success in a beetle. Animal
Behavior.(1987);38:503-509.
45. Poole, J.H. Mate guarding, reproductive
success and female choice in African
Elephants. Animal Behavior.(1989); 37:842-
849.
46. Hasselquist, D., Besch, S. & von Schantz, T.
Correlation between male song repertoire,
extra-pair paternity and offspring survival in
the great reed warbler. Nature.(1996);
381:229-232.
47. Sundberg, J. & Dixon, A. Old, colourful male
yellow hammers, Emberizacitrinella, benefit
from extra-pair copulations. Animal
Behavior.(1996);52:113-122.
48. Berven, K.A. Mate choice in the wood frog,
Ranasylvatica. Evolution. (1981); 35:707-
755
49. Alatalo, R., Gustafsson, L. & Lundberg, A.
Do females prefer older males in polygynous
bird species? The American Naturalist.
(1986);127:241-245.
50. Koenig, W.D. Levels of female choice in the
white-tailed skimmer Plathemislydia
(Odonata: Libelluliade). Behaviour. (1991);
119:193-224.
51. Petrie, M. Do peacock's trains advertise age?
Journal of Evolutionary Biology. (1993);
6:443-448.
...... 1
24 www.ijsir.co.in
P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

52. Olsson, M. & Madsen, T. Female choice or
male quantitative traits in lizards- Why is it so
rare? Behavioral Ecology and Sociobiology.
(1995);36:179-184.
53. Hansen, T.F. and Price, D.K. Good genes and
old age: do old mates provide superior genes?
Journal of Evolutionary Biology.(1995);
8:769-778.
54. Alatalo, R., Gustafsson, L. & Lundberg, A.
Do females prefer older males in polygynous
bird species? The American Naturalist.
(1986);127:241-245.
55. Price, D.K. & Hansen, T.F. How does
offspring quality change with age in male
Drosophila melanogaster? Behavioral
Genetics.(1998);28:395-402.
56. Beck, C.W. & Powell, L.A. Evolution of
female mate choice based on male age: Are
older males better mates? Evolutionary
EcologyResearch.(2000);2:107-118.
57. Jones, T.M., Balmford, A. &Quinnell, R.J.
Adaptive female choice for middle-aged
mates in a lekkingsandfly. Proceedings of the
Royal Society of London, Series B.(2000);
267:681-686.
58. Hemptinne, J.L., Dixon, A.F.G. & Adam, B.
Do males and females of the two-spot
ladybird, Adaliabipunctata (L.) differ in when
they mature sexually? Journal of Insect
Behavior.(2001);14(3):411-419.
59. Srivastava, S. and Omkar. Age specific
mating and reproductive senescence in seven
spotted ladybird, Coccinellaseptempunctata.
Journal of Applied Entomology. (2004); 128
(6):452-458
60. Pervez, A., Omkar and Richmond, A.S. The
influence of age on reproductive performance
of a predatory ladybird beetle, Propy-
leadissecta. Journal of Insect Science. USA.
(2004);4(22):1-8.
61. Omkar, Singh S. K. & Singh K. Effect of age
on reproductive attributes of an aphido-
phagous ladybird, Cheilomenessexmaculata.
Insect Science. (2006); 13( 4): 301–308,
August 2006
62. Fox, C.W., Hickman, D.L., Raleigh, E.L.,
&Mousseau, T.A. Paternal investment in a
seed beetle (Coleoptera: Bruchidae):
influence of male size, age, and mating
history. Annals of the Entomological Society
ofAmerica.(1995);88:101-103.
63. Wellington, W.G. Some maternal influences
on progeny quality in the western tent
caterpillar, Malcosomapluviale (Dyar).
CanadianEntomologist.(1965);97:1-14.
64. Harvey, G.T. Mean weight and rearing
performance of successive egg clusters of
eastern spruce budworm (Lepidoptera:
Tortricidae). Canadian Entomologist.(1977);
109:487-196.
65. Harvey, G.T. Environmental and genetic
effects on mean egg weight in spruce
budworm (Lepidoptera: Tortricidae). Cana-
dianEntomologist.(1983);115:1109-1117.
66. Richards, L.J. & Myers, J.H. Maternal
influences on size and emergence time of the
cinnabar moth. Canadian Journal of Zoology.
(1980); 58:1452-1457.
67. Jones, R.E., Hart, J.R. & Bull, G.D.
Temperature, size and egg production in the
cabbage butterfly, Pierisrapae L. Australian
Journalof Zoology.(1982);30:223-232.
68. Murphy, P.A., Giesel, J.T., &Manlove, M.N.
Temperature effects on life history variation in
Drosophila simulans. Evolution. (1983);
37:1181-1192.
69. Wiklund, C. &Persson, A. Fecundity, and the
relation of egg weight variation to offspring
fitness in the speckled wood butterfly
Parargeaegeria, or why don't butterfly
females lay more eggs? Oikos.(1983); 40:53-
63.
70. Karlsson, B. and Wiklund, C. Egg weight
variation and lack of correlation between egg
weight and offspring fitness in the wall brown
butterfly, Lassiommatamegera. Oikos.(1984);
43:367-385
71. Karlsson, B. and Wiklund, C. Egg weight
variation in relation to egg mortality and
starvation endurance of newly hatched larvae
in some satyrid butterflies. Ecological
Entomology.(1985);10:205-211.
72. Wiklund, C. &Karlsson, B. Egg size variation
in satyrid butterflies: adaptive vs historical
"Bauplan", and mechanistic explanations.
Oikos. (1984);43:391-400.
73. Navasero, R. and Elzer, G. Influence of
maternalageandhost deprivationon egg
...... 1
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