Future Of Nanomedicine In Diabetes Treatment||Nanomedicine||Diabetes||Classification Of Diabetes||Nanomedicine application for Glucose monitoring||Nanomedicine in management of diabetes||Diabetes test||LBL Technique||Glucose nanosensors||Carbon nanotubes||Quantum dots||Oral insulin||Microsphere||Microsphere for oral insulin production||Artificial pancreas||Nanopumps||Future of Nanomedicines||Introduction of Nanomedicines||Nanotechnology||

1. A
PROJECT REPORT
On
FUTURE OF NANOMEDICINE IN DIABETES TREATMENT
By
ABUL BASAR
B.Pharm, 4th
year
Roll No.- 001911401032
Session- 2022-23
Under the Guidance of
Dr. RANU BISWAS, PhD
Assistant Professor
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
JADAVPUR UNIVERSITY
Jadavpur, Kolkata-700032, West Bengal, India.
May 2023

2. DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
JADAVPUR UNIVERSITY
Jadavpur, Kolkata-700032, West Bengal, India.
CERTIFICATE from the SUPERVISOR
This is to certify that the Project Report entitled,”Future of nanomedicine in diabetes
treatment” has been carried out by ABUL BASAR, B.Pharm, 4th
year, under my guidance
for the partial fulfilment of the requirement for the degree of Bachelor of Pharmacy.
Date: Dr. RANUBISWAS
Place

3. ACKNOWLEDGEMENT
It is honor to carry out my project work under the guidance of Dr. Ranu Biswas, Assistant
Professor of the Department of Pharmaceutical Technology, Jadavpur University, Kolkata-
700032. I express my deepest gratitude, regard and respect to my project guide for suggesting
the subject of my project and rendering me her thoughtful and rational approach to this
project work.I am gently indebted to Dr. Ranu Biswas for her valuable guidance throughout,
which has enabled me to prepare this project work.
Date: ABUL BASAR
Place: Roll No.- 001911401032
B.Pharm, 4th
year

4. FUTURE OF NANOMEDICINE IN DIABETES TREATMENT
ABSTRACT:
The combination of nanotechnology and medicine has created a new field “Nano medicine”
to enhance human health care. Nanomedicine is a specialized branch of medicine that applies
the fundamentals of nanotechnology to the prevention, diagnosis, and treatment of various
diseases, such as cancer, cardiovascular diseases, and diabetes. Worldwide around 425
million people have been affected by diabetes mellitus, the common approach of this
condition is a prescribed insulin replacement therapy, including injections of long-acting
insulin at mealtimes. Regarding the everyday routine, insulin injections and glucose tests can
be painful and time consuming for diabetic patients. Many efforts are given to overcome the
drawbacks of injection therapy, but there is the need for new safe and cost-effective
technologies for diagnosis and treatment. The major problems with conventional problems in
glucose self-monitoring are overcome by advances in nanomedicine, like Glucose nano
sensors, layer-by-layer (LBL) technique, Carbon Nanotubes and Quantum Dots (QD’s) etc.
INTRODUCTION:
According to the national centre for disease control(NCDC, INDIA) Diabetes in india has
risen from 7.1% in 2009 to 9% in 2022.Currently it has reached epidemic proportion among
the challenging unresolved health problems of the 21st century. Worldwide around 425
million people have been affected by diabetes and the number are expected to reach
around690 million by 2045 . Imbalance in body normal oxidative metabolism due to
excessive levels of either molecular oxygen or Reactive Oxygen Species (ROS) leads to high
glucose levels in blood (hyperglycemia) results in metabolic disturbances (oxidative stress)
and chronic complications in diabetes . The management of diabetic conditions by insulin
therapy has several drawbacks like insulin resistance and in chronic treatment causes

5. anaeroxia nervosa, brain atrophy and fatty liver. Currently several research studies are going
on with the aid of nano size particles to overcome such limitations in diabetes management.
Nanotechnology can be defined as the science and engineering involved in the design,
synthesis, characterization and application of materials and devices whose smallest functional
organization in at least one dimension is on the nanometer scale (one-billionth of a meter) .
When this science is applied specifically to the problems of medicine, it is called
‘Nanomedicine’ . The nanomedicine scale limitations excludes at the lower end atoms (0.1
nm) and at the upper end biological entities such as bacteria (1000–10000 nm) and body cells
(eg. White blood cell 10000 nm).Human body has configured many of its biocomponents as
nanostructures, including proteins, mitochondria, ion channels, membranes, secretory
granules, lysosomes and so on, but many new nanomaterials and structures are now being
manufactured that might be of use in medicine, such as nanoparticles, capsules, films and
tubes, and complex molecules( e.g fullerenes) . Nanomedicine can be classified into (a)
measurement (or ‘nanometrology’), which concerns either measuring very small amounts of
analytes (e.g.microphysiometer) or using very smallsized devices for measuring (e.g.
Quantum dots). (b) Therapy, as all of the manipulations and constructions of materials at the
nano-level ultimately concern therapies (e.g. Artificial nanopancreas).
CLASSIFICATION OF DIABETES:
Diabetes is a heterogeneous complex metabolic disorder characterized by elevated blood
glucose concentration secondary to either resistance to the action of insulin, insufficient
insulin secretion, or both . The major clinical manifestation of the diabetic state is
hyperglycemia. However, insulin deficiency and/or insulin resistance also are associated with
abnormalities in lipid and protein metabolism, and with mineral and electrolyte disturbances.
The vast majority of diabetic patients are classified into four categories: Mainly type 1

6. diabetes mellitus, which is caused by an absolute or near absolute deficiency of insulin, or
type 2 diabetes mellitus, which is characterized by the presence of insulin resistance with an
inadequate compensatory increase in insulin secretion
I. Type 1 diabetes (beta-cell destruction, usually leading to absolute insulin
deficiency)
The combination of nanotechnology and medicine has created a new field “Nano medicine”
to enhance human health care. Nanomedicine is a specialized branch of medicine that applies
the fundamentals of nanotechnology to the prevention, diagnosis, and treatment of various
diseases, such as cancer, cardiovascular diseases, and diabetes. Worldwide around 425
million people have been affected by diabetes mellitus, the common approach of this
condition is a prescribed insulin replacement therapy, including injections of long-acting
insulin at mealtimes. Regarding the everyday routine, insulin injections and glucose tests can
be painful and time consuming for diabetic patients. Many efforts are given to overcome the
drawbacks of injection therapy, but there is the need for new safe and cost-effective
technologies for diagnosis and treatment. The major problems with conventional problems in
glucose self-monitoring are overcome by advances in nanomedicine, like Glucose nano
sensors, layer-by-layer (LBL) technique, Carbon Nanotubes and Quantum Dots (QD’s) etc. In
this review, the chief scientific and technical aspects of nanomedicine related to diabetes and
some pros and cons of nanotechnology-based nanomedicine are discussed.
II. Type 2 diabetes (may range from predominantly insulinresistance with relative
insulin deficiency to a predominantly insulin secretory defect with insulin
resistance)
Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with
relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is
believed to involve the insulin receptor. Diabetes mellitus cases due to a known defect are
classified separately. In the early stage of diabetes type 2, the predominate abnormalities is
reduced insulin sensitivity. At this stage of diabetes hyperglycaemia can be reversed by a

7. variety of measures and medication that improve insulin sensitivity or reduced glucose
production in liver. Type 2 diabetes is due to primarily to lifestyle factors and genetics. A
number of lifestyle factors are known to be important to the development of type 2 diabetes,
including obesity (defined by a body mass index of greater than thirty), lack of physical
activity, poor diet, stress, and urbanization. Dietary factors also influence the risk of
developing type2 diabetes. Consumption of sugar-sweetened drinks in excess is associated
with an increased risk. The type of fats in the diet is als important, with saturated fats and
trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing
the risk.
III. Gestational Diabetes mellitus (GDM)
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving
a combination of relatively inadequate insulin secretion and responsiveness. Gestational
diabetes is found to have diabetes mellitus, most commonly type 2 Gestational diabetes is
fully treatable, but requires careful medical supervision throughout the pregnancy.
Management may include dietary changes, blood glucose monitoring, and in some cases,
insulin may be required. The third trimester of pregnancy is reported to be the onset of the
disorder in most women with GDM. Untreated gestational diabetes can damage the health of
the foetus or mother. Risks to the baby include macrosomia (high birth weight), congenital
cardiac and central nervous system anomalies, and skeletal muscle malformations.
IV. Other specific types
• Genetic defects of beta -cell function
• Genetic defects in insulin action
• Diseases of the exocrine pancreas
• Endocrinopathies
• Drug- or chemical-induced

8. DIABETES TEST AND DIAGNOSIS :
Doctors use a variety of tests to diagnose diabetes and prediabetes. Your doctor may
recommend different tests depending on whether you have symptoms or not, or whether you
are pregnant.
• Fasting plasma glucose test
The fasting plasma glucose (FPG) test measures your blood glucose level at a single point in
time. For the most reliable results, your doctor will give you the test in the morning after you
have fasted for at least 8 hours. Fasting means having nothing to eat or drink except sips of
water.
• A1C test
The A1C test is a blood test that provides your average levels of blood glucose over the last 3
months. Other names for the A1C test are hemoglobin A1C, HbA1C, glycated hemoglobin,
and glycosylated hemoglobin test. You can eat and drink before this test. Before using the
A1C test to diagnose diabetes, your doctor will consider factors, such as whether you are in
your second or third trimester of pregnancy or whether you have certain types of anemia NIH
external link or another problem with your blood. The A1C test might not be accurate in
those cases.
Certain types of hemoglobin, called hemoglobin variants, can interfere with measuring A1C
levels. Most A1C tests used in the United States are not affected by the most common
variants. If your A1C test results and blood glucose levels do not match, your doctor should
consider that the A1C test may not be a reliable test for you.
Your doctor will report your A1C test result as a percentage, such as an A1C of 7%. The
higher the percentage is, the higher your average blood glucose levels are.

9. • Random plasma glucose test
Sometimes doctors use the random plasma glucose test to diagnose diabetes when you have
symptoms of diabetes and they do not want to wait until you have fasted for 8 hours. You
may have this blood test at any time.
• Glucose challenge test
If you are pregnant, your doctor might test you for gestational diabetes with the glucose
challenge test. Another name for this test is the glucose screening test. In this test, a health
care professional will take a sample of your blood 1 hour after you drink a sweet liquid
containing glucose. You do not need to fast for this test. If your blood glucose level is too
high—135 mg/dL to 140 mg/dL or higher—you may need to return for an oral glucose
tolerance test while fasting.
• Oral glucose tolerance test
The oral glucose tolerance test (OGTT) helps doctors detect type 2 diabetes, prediabetes, and
gestational diabetes. However, the OGTT is a more expensive test than the FPG test and the
glucose challenge test, and it is not as easy to give.
Before the test, you will need to fast for at least 8 hours. A health care professional will take a
blood sample to measure your glucose level after fasting. Next, you will drink a liquid that is
high in sugar. Another blood sample is taken 2 hours later to check your blood glucose level.
If your blood glucose level is high, you may have diabetes.
If you are pregnant, your blood will be drawn every hour for 2 to 3 hours. If your blood
glucose levels are high two or more times during the OGTT, you may have gestational
diabetes.

10. • Test results for diagnosis of prediabetes and diabetes
Diagnosis A1C
Fasting Plasma
Glucose
Oral Glucose Tolerance
Test*
Random Plasma Glucose
Test‡
Normal below 5.7% 99 mg/dL or below 139 mg/dL or below N/A
Prediabetes
5.7% to
6.4%
100 to 125 mg/dL 140 to 199 mg/dL N/A
Diabetes
6.5% or
above
126 mg/dL or above 200 mg/dL or above 200 mg/dL or above
NANOMEDICINE APPLICATION IN GLUCOSE MONITORING:
The major problems with conventional finger-prick capillary blood glucose self monitoring
are widely accepted. It is painful (leading to non-compliance) and cannot be performed when
the patient is sleeping or driving a motor vehicle (times when the patient is especially
vulnerable to hypoglycaemia) and, because it is intermittent, it can miss dangerous
fluctuations in blood glucose concentrations between tests. Currently in market several
implanted needle-type enzyme electrodes or microdialysis probes are available for continuous
glucose monitoring but those are limited impaired responses and unpredictable signal drift in
vivo, and also need calibration against capillary glucose tests and contributes to sensor
inaccuracies. The repeated insertion of the sensor probe is also semi-invasive.
o Glucose nanosensors
Improved nanotechnique for in vivo glucose monitoring is a ‘smart tattoo’ composed of
glucose-responsive, fluorescence-based nanosensors implanted into the skin but interrogated
from outside the body, thus gives non-invasive measurements. In this method sensors that use
fluorescence for detecting analyte changes have some advantages compared to the more usual
implantedelectrochemical electrodes, as they should not be susceptible to electroactive tissue

11. interfearence that contribute to the instability of present sensors, and because Near infrared
(NIR) light with a wavelength above about 600 nm passes through several centimeters of
tissue, allowing implantation and non-invasive measurement at the body surface. Currently a
number of biological or artificial receptors for glucose have been described, which can
transduce glucose concentrations into changes in fluorescence, including lectins (plant lectin
concanavalin-A) , enzymes (hexokinase), bacterial binding proteins(l Glucose/Galactose-
Binding Protein (GBP) and boronic acid derivatives and which might be engineered as
nanosensors.
o Layer by Layer Technique
Layer-by-Layer method (LbL) is a thin film fabrication technique. The films are formed by
depositing alternating layers of oppositely charged materials. The layers can be performed in
different ways e.g. dip coating, spin-coating, spray-coating. Various materials can be
deposited by LbL method including polyions, metals, ceramics, nanoparticles, and biological
molecules.
The aim of our work is to produce silica-coated alginate particles with specific controllable
shell structure for applications in drug and other chemicals delivery. The silica shell can be
made by electrostatic Layer by Layer assembly of silica nanoparticles on the surface of
alginate microparticles. Alginate particles as well as silica nanoparticles are negatively
charged, therefore the positively charged polyelectrolyte Poly(dimethyldiallylamonium
chloride) (PDDA) is used as a “binder”.
We use dip coating with following steps:
1. Poly(dimethyldiallylamonium chloride) – PDDA (positively charged)
2. Washing
3. Silica nanoparticles – silica np (negatively charged)
4. Washing
Then 1.-4. are repeated till the coating reachs the desired thickness.

12. o Carbon nanotubes
Carbon nanotubes discovered in 1991 are tubular structures like a sheet of graphite rolled into
a cylinder capped at one or both ends by a buckyball. Nanotubes can be Single Walled
Carbon Nanotube (SWCNT) or Multiwalled Carbon Nanotube (MWCNT) in concentric
fashion. The microphysiometer is built from multiwalled carbon nanotubes, which are like
several flat sheets of carbon atoms stacked and rolled into very small tubes. Which are like
several flat sheets of carbon atoms stacked and rolled into very small tubes. The nanotubes
are electrically conductive and the concentration of insulin in the chamber can be directly
related to the current at the electrode and the nanotubes operate reliably at pH levels
characteristic of living cells. Current detection methods measure insulin production at
intervals by periodically collecting small samples and measuring their insulin levels. The new
sensor detects insulin levels continuously by measuring the transfer of electrons produced
when insulin molecules oxidize in the presence of glucose. When the cells produce more
insulin molecules, the current in the sensor increases and vice versa, allowing monitoring
insulin concentrations in real time.
o Quantum dots
Quantum Dots (QDs) can be used for biomedical purposes as a diagnostic as well as
therapeutic tool. These arenanosized (2-10 nm) semiconductor crystals, such as cadmium
selenide, coated with a shell, such as zinc sulfide. QDs have been used as a fluorescent probe
in several biosensor applications, often using As Fluorescence-Resonance Energy Transfer
(FRET), because they display high-intensity fluorescence that is excitable over a broad range

13. of wavelengths, but have an emission wavelength that is dependent on the particle size. For
example, based a glucose sensor on FRET between QDs as a fluorescence donor and gold
nanoparticles as an acceptor the, glucose displaces concanavalin A-labeled QDs from gold-
labeled cyclodextrin, thereby, reducing FRET and increasing fluorescence.
NANOMEDICINE IN MANAGEMENT OF DIABETES:-
Worldwide million of peoples are suffering with a pervasive, chronic and often insidious
diabetes is caused by inability of the pancreas to control the blood glucose concentration. The
preferred approach of insulin intake since the past decades is via subcutaneous route, which,
nonetheless, often fails to mimic the glucose homeostasis observed in normal subjects
because in this approach insulin delivered to the peripheral circulation rather than to the
portal circulation and directly into the liver, which is the physiological route in normal
individuals. Furthermore, multiple daily injections of insulin referred for poor patient
compliance are associated with subcutaneous route treatment. Therefore, many studies were
done to find out the better and safer route of insulin administration, in this regards application
of nanotechnology in medicine revealed a solution to overcome this problem.
• Oral insulin
In diabetic patients oral administration of insulin can be beneficial not only to alleviate the
pain and trauma caused by injections, but it can mimic the physiological fate of insulin as
well. However, oral administration of protein drugs, such as insulin, encounters difficulties
with low pH of gastric medium in the stomach and its digestive enzymes as well as intestinal
epithelium is a major barrier to the absorption of molecular weight hydrophilic
macromolecules (e.g proteins, polysaccharides and nucleic acids) before it reach the target
cell for it specific action. Therefore, attentions have been given to improving the paracellular
delivery of hydrophilic macromolecules with the application of nanotechnology in diabetic
research [40]. The nanomedicine technologies that may be employed for oral insulin delivery

14. include prodrugs (insulin–polymer .conjugation), micelles, liposomes , solid lipid
nanoparticles (NPs) and NPs of biodegradable polymers. formulation is PEGylation (i.e.,
drug conjugation to Polyethylene Glycol [PEG]) for enhanced solubility, permeability and
stability. Insulin–PEG prodrugs have shown great advantages in oral delivery. ScottMoncrieff
et al. developed a system of bilesalt and fattyacid mixed micelles and found that those
micelles containing 30 mM sodium glycocholate and 40 mM linoleic acid significantly
improved enteral insulin absorption. Unfortunately, micelles did not seem to be ideal for
delivery of hydrophilic drugs. Instead, liposomes can have much better performance for oral
insulin delivery. This liposomal delivery system containing glycocholate as an enzyme
inhibitor and permeat ion enhancer has been developed recently for oral insulin delivery,
which showed better protect ion of insulin against enzymatic degradation by pepsin, trypsin
and achymotrypsin. NPs of US FDAapproved biodegradable polymers, such as poly
(lacticcoglycolic acid) (PLGA) and polycaprolactone, were also investigated for oral insulin
delivery. However, those NPs may not be ideal for delivery of hydrophilic drugs.
Nevertheless, how it can be applied to oral delivery for hydrophilic drugs such as insulin is
still a challenge.
Therefore, attention has been given to improving the paracellular transport of hydrophilic
drugs. A variety of intestinal permeation enhancers including chitosan (CS) have been used
for the assistance of the absorption of hydrophilic macromolecules. Therefore, a carrier
system is needed to protect protein drugs from the harsh environment in the stomach and
small intestine, if given orally. Additionally, CS nanoparticles (NPs) enhanced the intestinal
absorption of protein molecules to a greater extent than aqueous solutions of CS in vivo. The
insulin loaded NPs coated with muco adhesive CS may prolong their residence in the small
intestine, infiltrate into the mucus layer and subsequently mediate transiently opening the
tight junctions between epithelial cells while becoming unstable and broken apart due to their

15. pH sensitivity and/or degradability. The insulin released from the broken-apart NPs could
then permeate through the paracellular pathway to the bloodstream, its ultimate destination.
• Microsphere for oral insulin production
The most promising strategy to achieve oral insulin is the use of a microsphere system which
is inherently a combination strategy. Microspheres act both as protease inhibitors by
protecting the encapsulated insulin from enzymatic degradation within its matrix and as
permeation enhancers by effectively crossing the epithelial layer after oral administration.
• Artificial pancreas
Development of artificial pancreas could be the permanent solution for diabetic patients. The
original idea was first described in 1974. The concept of its work is simple: a sensor electrode
repeatedly measures the level of blood glucose; this information feeds into a small computer
that energizes an infusion pump, and the needed units of insulin enter the bloodstream from a
small reservoir. Another way to restore body glucose is the use of a tiny silicon box that
contains pancreatic beta cells taken from animals. The box is surrounded by a material with a
very specific nanopore size (about 20 nanometers in diameter). These pores are big enough to
allow for glucose and insulin to pass through them, but small enough to impede the passage
of much larger immune system molecules. These boxes can be implanted under the skin of
diabetes patients. This could temporarily restore the body’s delicate glucose control feedback
loop without the need of powerful immunosuppressant that can leave the patient at a serious
risk of infection. Scientists are also trying to create a nanorobot which would have insulin
departed in inner chambers, and glucose level sensors on the surface. When blood glucose
levels increase, the sensors on the surface would record it and insulin would be released. Yet,

16. this kind of nano-artificial pancreas is still only a theory.
• Nanopumps
The nanopump is a powerful device and has many possible applications in the medical field.
The first application of the pump, introduced by Debiotech for insulin delivery. The pump
injects insulin to the patient’s body in a constant rate, balancing the amount of sugars in his or
her blood. The pump can also administer small drug doses over a long period of time.
THE FUTURE PERSPECTIVES:
What can we expect from nanomedicine applied to diabetes management in the future? There
is likely to be targeted imaging of diabetes complications, probably using antibodies or other
molecules with an affinity for specific tissues and linked to a NIR-emitting fluorophore-
labeled or MRI-visible nanoparticle. QDs with their strong fluorescence may be suitable
fluorescent probes for imaging, probably passivated with silica to improve biocompatibility.

17. Similarly, targeted drug delivery might use an antibody linked to a nanovesicle containing a
specific drug for delivery directed at, for example, the liver.
Nanosized machines (‘nanorobots’) that circulate in the body, identifying disease and
repairing and treating it have long been the subject of conjecture in nanotechnology and
popular literature, and these devices continue be the subject of speculation in diabetes
research. Medical nanorobots, in a sophisticated sense of a machine with moving parts, seem
to be far from clinical reality, but some automatic coupling of metabolite or disease-related
tissue sensing with treatment in an integrated nanodevice or structure, which has been called
‘theranostics’, is quite possible. For example, there are several ongoing attempts to make a
glucose-controlled insulin delivery system. One approach might be to use vesicles made of
oxidation-sensitive polymers and containing glucose oxidase Citation and insulin. Hydrogen
peroxide produced by the oxidation of glucose solubilizes the membrane of the vesicle, and if
the vesicles were to contain insulin, it might be released in proportion to the glucose
concentration.
To conclude, there are many exciting opportunities for research and development in
nanomedicine applied to diabetes, and translation to routine clinical practice in at least some
areas is not far away.
CONCLUSION:
This project was the aspects of the futureof nanomedicine in related to diabetes. However the
expectation form nanotechnology in medicine are high and the potential benefits are
endlessly enlisted, the safety of nanomedicine is not yet clear. Nanomedicine shows great
potential for the future diabetic management and at the moment the suggested benefits in
diabetic health care outweigh the possible dangers of nanoparticles use in medicine. Here we
conclude that use of nanomedicine in diabetic care is in initial stage, but progress is rapid.

18. Diabetes has many remaining problems; nanomedicine is likely to be a key technology for
solving many of them and will be a core technology in diabetic research.
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