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PRESENTED BY- GUIDED BY-
Mr. Shubham J. Gore Dr. V.V. Pande
F.Y.M Pharm HOD of Pharmaceutics
(Pharmaceutics) Department.
Sanjivani College of Pharmaceutical Education and Research,
Kopargaon.
116 March 2018
 Introduction
 Structure & components
 Classification
 Mechanism
 Method of preparation
 Characterization
 Uses
 List of marketed product
 Niosome
 Diff.between liposome & niosome
 Advanced method of niosome
 Application
 Recent advances in niosome
 Conclusion
 References
216 March 2018
 liposomes are simple, microscopic, concentric bilayered
vesicles in which an aqueous volume is entirely
enclosed by a membraneous lipid bilayer mainly
composed of natural or synthetic phospholipids.
 Liposomes were first produced in England in 1961 by
Alec D. Bangham.The size of a liposome ranges from
some 20 nm up to several micrometers.
 Phospholipid + Cholesterol
316 March 2018
416 March 2018
 Phospholipid
Phospholipid are amphipathic molecule i.e. having affinity for both
aqueous & polar moieties, as they have a hydrophobic tail & hydrophillic
head.
 Hydrophilic polar head-
Phosphoric acid bound to water soluble molecule.
 Hydrophobic tail-
2 fatty acid chain containing 10-24 carbon atoms and 0-6 double bond in
each chain.
Naturally occurring phospholipids used are :
 PC: Phosphatidyl choline.(lecithin)
 PE: Phosphatidyl ethanolamine.(cephalin)
 PS: Phosphatidylserine
516 March 2018
 Synthetic phospholipids used are:
DOPC: Dioleoyl phosphatidyl choline
DSPC: Disteroyl phosphatidyl choline
DOPE: Dioleoyl phosphatidyl ethanolamine
DSPE: Distearoyl phosphatidyl ethanolamine
 Cholesterol
 Cholesterol stabilizes the Membrane
 Steroid lipid
 Interdigitates between phospholipids
 It’s decreases the fluidity in bilayer
616 March 2018
716 March 2018
816 March 2018
16 March 2018 9
16 March 2018 10
1116 March 2018
 General Method Of Liposome Preparation
12
Drying down lipid from organic solvent
Dispersion of lipid in aqueous media
Purification of resultant liposome
Analysis of final product
16 March 2018
 Mechanical Dispersion Method.
13
Lipid dissolve in organic solvent/co-solvent
Remove organic solvent under vacuum
Film deposition
Solid lipid mixture is hydrated by using aqueous buffer
Lipid spontaneously swell & Hydrate
Liposome
16 March 2018
 There are four basic method for mechanical
dispersion.
 Hand shaking method.
 Non shaking method.
 Pro –liposomes .
 Freeze drying .
1416 March 2018
1516 March 2018
1616 March 2018
1716 March 2018
1816 March 2018
1916 March 2018
2016 March 2018
2116 March 2018
2216 March 2018
2316 March 2018
 Extrusion of preformed
large liposomes in french
press under very high
pressure .
 uni or oligo lamellar
liposomes of intermediate
size (30-80nm ) .
 Advantages
 Less leakage and more
stable liposomes are
formed compared to
sonicated forms.
2416 March 2018
 The size of
liposomes is reduced
by gently passing
them through
polycarbonate
membrane filter of
defined pore size at
lower pressure
 Used for preparation
of LUVs and MLVs
2516 March 2018
2616 March 2018
27
Lipid dissolved in organic solvent
Excess addition of aqueous phase
Lipid allign at interface of aqueous and organic layer
Formation of monolayer and bilayer of phospholipid
LIPOSOME
16 March 2018
 Ether Injection
Lipid +ether solution in
syringe
Inject slowly
In the aqueous phase
Large unilamellar
vesicle
28
 Ethanol injection
Lipid+ethanol solution in
the syringe
Inject rapidly
In the aqueous phase
Small unilamellar vesicle
16 March 2018
Organic solution +Lipid+aqueous phase
Emulsion
Hot aqueous solution of buffer
Multi compartment vesicle W/O/W (double
emulsion)
LUVs
2916 March 2018
Emulsion
Evaporation under reduced pressure, rotary
evaporator
Semi solid gel
Shake to get LUVs
3016 March 2018
Below CMC detergent molecules exist in free
solution.As the conc.is increased , micelle
are formed.
31
Phospholipid brought into intimate contact with aqueous phase
By addition optimized conc.of detergent
Formation of micelle (LIPOSOME)
16 March 2018
3216 March 2018
3316 March 2018
 In gene delivery.
 As drug delivery carriers.
 Enzyme replacement therapy.
 Chelation therapy for treatment of heavy metal
poisoning.
 Liposomes in antiviral/anti microbial therapy.
 In multi drug resistance.
 In tumour therapy.
 In immunology.
 In cosmetology
3416 March 2018
3516 March 2018
Phase-I Phase-II Phase-III
LEM-ETU
(Mitoxantrone
liposomes
Grb-2
(Antisense protein
liposomes)
INX-0076
(Topotecan
Sphingosomes)
INX0125
Vinorelbine
sphingosomes
LiplaCis
(Cisplatin
liposomes)
Aroplatia
(Platinum
analogue
Liposomes)
S-ANNA
(Annamycin
Liposomes)
SPJ-077
(Cisplatin
Liposomes)
OSI-211
(Lurtorecan
Liposomes)
S-CKD602
(CKD 602
Liposomes)
Arikace
(Amikacin
Liposomes)
Stimuvax
(Tecemotide
liposomes)
T4NS
(T4 Endonuclease
V
Liposomes)
Liptrostin
(PGE-Liposomes)
Thermodox
(Doxorubicin
Liposomes)
 INTRODUCTION
 Niosomes are a novel drug delivery system, in which
the medication is encapsulated in a vesicle.
 The vesicle is composed of a bilayer of non-ionic
surface active agents and hence the name niosomes.
 The niosomes are very small, and microscopic in size.
Their size lies in the nanometric scale.
 materials have been used to form niosomes such as
sucrose ester surfactants and polyoxyethylene alkyl
ether surfactants, alkyl ester, alkyl amides, fatty acids
and amino acid compound.
3716 March 2018
 Ester bonds of phospholipids are
easily hydrolyzed, this can lead to
phosphoryl migration at low PH.
 Peroxidation of unsaturated
phospholipids.
 As liposomes have purified
phospholipids they are to be stored
and handled at inert(N2)
atmospheres where as Niosomes
are are made of non ionic
surfactants and are easy to handle
and store.
 Phospholipid raw materials are
naturally occurring substances and
as such require extensive
purification thus making them
costly. 3816 March 2018
3916 March 2018
 Hand Shaking method
 Reverse phase evaporation technique
 Ether Injection method
 Multiple membrane extrusion method
 Bubble method
 Sonication
 From Proniosomes
4016 March 2018
 BUBBLE METHOD
It is novel technique
for the one step
preparation of
liposomes and
niosomes without the
use of organic
solvents.
RBF as bubbling unit with
three necks in water bath.
Reflux , thermometer and
nitrogen supply by three
necks
Cholesterol+ Surfactant
dispersed in buffer pH 7.4
at 70°C
Above dispersion is
homogenized for 15 sec and
then bubbled with nitrogen
gas at 70°C to get niosomes
4116 March 2018
42
Formation of niosomes from proniosomes:
It is prepared by coating water-soluble carrier such as
sorbitol with surfactant. The result of the coating process
is a dry formulation. In which each water-soluble particle
is covered with a thin film of dry surfactant.This
preparation is termed “Proniosomes
16 March 2018
 Transdermal
 parenteral
 Radiopharmaceuticals
 Opthalmic drug delivery
 Leishmeniasis
 Cancer
 Diagnostic imaging
- Visual representation of the fuction of organ.
4316 March 2018
 Combination of PEG and glucose conjugates on the surface of
niosomes significantly improved tumor targeting of an
encapsulated paramagnetic agent assessed with MR imaging in a
human carcinoma xenograft model.
 Phase I and phase II studies were conducted for Niosomal
methotrexate gel in the treatment of localized psoriasis. These
studies suggest that niosomal methotrexate gel is more
efficacious than placebo and marketed methotrexate gel.
 A research article was published that Acyclovir entrapped
niosomes were prepared by Hand shaking and Ether injection
methods increases the oral bioavailability.
 Lancome has come out with a variety of anti-ageing products
which are based on niosome formulations.
4416 March 2018
 The concept of incorporating the drug into liposomes or
niosomes for a better targeting of the drug at appropriate tissue
destination is widely accepted by researchers and academicians.
 Niosomes represent a promising drug delivery module.
 Niosomes are thoughts to be better candidates drug delivery as
compared to liposomes due to various factors like cost, stability
etc .
 Various type of drug deliveries can be possible using niosomes
like targeting, ophthalmic, topical, parenteral, etc.
 Niosomes can also serve better aid in diagnostic imaging and
vaccine adjuvant in pharmaceutical industry.s
4516 March 2018
 S.P. Vyas And R.K. Khar,targeted & Controlled Drug
Delivery,liposomes,173-279.
 Avinash Kumar Seth and Ambika Nandan Misra (2007),“Preparation
and evaluation of Acyclovir Liposome’s by two techniques a
comparative study”, Indian Journal of Pharmaceutical sciences, Vol. 6,
No. 2, pp.75-81
 Himanshu Anwekar, Liposome- as drug carriers, International Journal
Of Pharmacy & Life Sciences, Vol.2, Issue 7: July: 2011, 945-951
 Upendra Bulbake , Sindhu Doppalapudi,Review on Liposomal
Formulations in Clinical Use:Pharmaceutics, Published: 27 March
2017.
4616 March 2018
Semisolid based niosome………7marks
(2015)
16 March 2018 47
4816 March 2018

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Liposome and Niosome

  • 1. PRESENTED BY- GUIDED BY- Mr. Shubham J. Gore Dr. V.V. Pande F.Y.M Pharm HOD of Pharmaceutics (Pharmaceutics) Department. Sanjivani College of Pharmaceutical Education and Research, Kopargaon. 116 March 2018
  • 2.  Introduction  Structure & components  Classification  Mechanism  Method of preparation  Characterization  Uses  List of marketed product  Niosome  Diff.between liposome & niosome  Advanced method of niosome  Application  Recent advances in niosome  Conclusion  References 216 March 2018
  • 3.  liposomes are simple, microscopic, concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membraneous lipid bilayer mainly composed of natural or synthetic phospholipids.  Liposomes were first produced in England in 1961 by Alec D. Bangham.The size of a liposome ranges from some 20 nm up to several micrometers.  Phospholipid + Cholesterol 316 March 2018
  • 5.  Phospholipid Phospholipid are amphipathic molecule i.e. having affinity for both aqueous & polar moieties, as they have a hydrophobic tail & hydrophillic head.  Hydrophilic polar head- Phosphoric acid bound to water soluble molecule.  Hydrophobic tail- 2 fatty acid chain containing 10-24 carbon atoms and 0-6 double bond in each chain. Naturally occurring phospholipids used are :  PC: Phosphatidyl choline.(lecithin)  PE: Phosphatidyl ethanolamine.(cephalin)  PS: Phosphatidylserine 516 March 2018
  • 6.  Synthetic phospholipids used are: DOPC: Dioleoyl phosphatidyl choline DSPC: Disteroyl phosphatidyl choline DOPE: Dioleoyl phosphatidyl ethanolamine DSPE: Distearoyl phosphatidyl ethanolamine  Cholesterol  Cholesterol stabilizes the Membrane  Steroid lipid  Interdigitates between phospholipids  It’s decreases the fluidity in bilayer 616 March 2018
  • 12.  General Method Of Liposome Preparation 12 Drying down lipid from organic solvent Dispersion of lipid in aqueous media Purification of resultant liposome Analysis of final product 16 March 2018
  • 13.  Mechanical Dispersion Method. 13 Lipid dissolve in organic solvent/co-solvent Remove organic solvent under vacuum Film deposition Solid lipid mixture is hydrated by using aqueous buffer Lipid spontaneously swell & Hydrate Liposome 16 March 2018
  • 14.  There are four basic method for mechanical dispersion.  Hand shaking method.  Non shaking method.  Pro –liposomes .  Freeze drying . 1416 March 2018
  • 24.  Extrusion of preformed large liposomes in french press under very high pressure .  uni or oligo lamellar liposomes of intermediate size (30-80nm ) .  Advantages  Less leakage and more stable liposomes are formed compared to sonicated forms. 2416 March 2018
  • 25.  The size of liposomes is reduced by gently passing them through polycarbonate membrane filter of defined pore size at lower pressure  Used for preparation of LUVs and MLVs 2516 March 2018
  • 27. 27 Lipid dissolved in organic solvent Excess addition of aqueous phase Lipid allign at interface of aqueous and organic layer Formation of monolayer and bilayer of phospholipid LIPOSOME 16 March 2018
  • 28.  Ether Injection Lipid +ether solution in syringe Inject slowly In the aqueous phase Large unilamellar vesicle 28  Ethanol injection Lipid+ethanol solution in the syringe Inject rapidly In the aqueous phase Small unilamellar vesicle 16 March 2018
  • 29. Organic solution +Lipid+aqueous phase Emulsion Hot aqueous solution of buffer Multi compartment vesicle W/O/W (double emulsion) LUVs 2916 March 2018
  • 30. Emulsion Evaporation under reduced pressure, rotary evaporator Semi solid gel Shake to get LUVs 3016 March 2018
  • 31. Below CMC detergent molecules exist in free solution.As the conc.is increased , micelle are formed. 31 Phospholipid brought into intimate contact with aqueous phase By addition optimized conc.of detergent Formation of micelle (LIPOSOME) 16 March 2018
  • 34.  In gene delivery.  As drug delivery carriers.  Enzyme replacement therapy.  Chelation therapy for treatment of heavy metal poisoning.  Liposomes in antiviral/anti microbial therapy.  In multi drug resistance.  In tumour therapy.  In immunology.  In cosmetology 3416 March 2018
  • 36. Phase-I Phase-II Phase-III LEM-ETU (Mitoxantrone liposomes Grb-2 (Antisense protein liposomes) INX-0076 (Topotecan Sphingosomes) INX0125 Vinorelbine sphingosomes LiplaCis (Cisplatin liposomes) Aroplatia (Platinum analogue Liposomes) S-ANNA (Annamycin Liposomes) SPJ-077 (Cisplatin Liposomes) OSI-211 (Lurtorecan Liposomes) S-CKD602 (CKD 602 Liposomes) Arikace (Amikacin Liposomes) Stimuvax (Tecemotide liposomes) T4NS (T4 Endonuclease V Liposomes) Liptrostin (PGE-Liposomes) Thermodox (Doxorubicin Liposomes)
  • 37.  INTRODUCTION  Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle.  The vesicle is composed of a bilayer of non-ionic surface active agents and hence the name niosomes.  The niosomes are very small, and microscopic in size. Their size lies in the nanometric scale.  materials have been used to form niosomes such as sucrose ester surfactants and polyoxyethylene alkyl ether surfactants, alkyl ester, alkyl amides, fatty acids and amino acid compound. 3716 March 2018
  • 38.  Ester bonds of phospholipids are easily hydrolyzed, this can lead to phosphoryl migration at low PH.  Peroxidation of unsaturated phospholipids.  As liposomes have purified phospholipids they are to be stored and handled at inert(N2) atmospheres where as Niosomes are are made of non ionic surfactants and are easy to handle and store.  Phospholipid raw materials are naturally occurring substances and as such require extensive purification thus making them costly. 3816 March 2018
  • 40.  Hand Shaking method  Reverse phase evaporation technique  Ether Injection method  Multiple membrane extrusion method  Bubble method  Sonication  From Proniosomes 4016 March 2018
  • 41.  BUBBLE METHOD It is novel technique for the one step preparation of liposomes and niosomes without the use of organic solvents. RBF as bubbling unit with three necks in water bath. Reflux , thermometer and nitrogen supply by three necks Cholesterol+ Surfactant dispersed in buffer pH 7.4 at 70°C Above dispersion is homogenized for 15 sec and then bubbled with nitrogen gas at 70°C to get niosomes 4116 March 2018
  • 42. 42 Formation of niosomes from proniosomes: It is prepared by coating water-soluble carrier such as sorbitol with surfactant. The result of the coating process is a dry formulation. In which each water-soluble particle is covered with a thin film of dry surfactant.This preparation is termed “Proniosomes 16 March 2018
  • 43.  Transdermal  parenteral  Radiopharmaceuticals  Opthalmic drug delivery  Leishmeniasis  Cancer  Diagnostic imaging - Visual representation of the fuction of organ. 4316 March 2018
  • 44.  Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.  Phase I and phase II studies were conducted for Niosomal methotrexate gel in the treatment of localized psoriasis. These studies suggest that niosomal methotrexate gel is more efficacious than placebo and marketed methotrexate gel.  A research article was published that Acyclovir entrapped niosomes were prepared by Hand shaking and Ether injection methods increases the oral bioavailability.  Lancome has come out with a variety of anti-ageing products which are based on niosome formulations. 4416 March 2018
  • 45.  The concept of incorporating the drug into liposomes or niosomes for a better targeting of the drug at appropriate tissue destination is widely accepted by researchers and academicians.  Niosomes represent a promising drug delivery module.  Niosomes are thoughts to be better candidates drug delivery as compared to liposomes due to various factors like cost, stability etc .  Various type of drug deliveries can be possible using niosomes like targeting, ophthalmic, topical, parenteral, etc.  Niosomes can also serve better aid in diagnostic imaging and vaccine adjuvant in pharmaceutical industry.s 4516 March 2018
  • 46.  S.P. Vyas And R.K. Khar,targeted & Controlled Drug Delivery,liposomes,173-279.  Avinash Kumar Seth and Ambika Nandan Misra (2007),“Preparation and evaluation of Acyclovir Liposome’s by two techniques a comparative study”, Indian Journal of Pharmaceutical sciences, Vol. 6, No. 2, pp.75-81  Himanshu Anwekar, Liposome- as drug carriers, International Journal Of Pharmacy & Life Sciences, Vol.2, Issue 7: July: 2011, 945-951  Upendra Bulbake , Sindhu Doppalapudi,Review on Liposomal Formulations in Clinical Use:Pharmaceutics, Published: 27 March 2017. 4616 March 2018