NIOSOMES
DEFINITION
• Niosome are non-ionic surfactant vesicles obtained on
hydration of synthetic nonionic surfactants with or
without incorporation of cholesterol or their lipids.
• They are structurally similar to liposomes in having a
bilayer however, the materials used to prepare niosomes
make them more stable and thus niosomes offer many
more advantages over liposomes.
• The sizes of niosomes are microscopic and lie in
nanometric scale.
• The particle size ranges from 10nm-100nm. 3
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STRUCTURE OF NIOSOME
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Figure-1 Structure of Niosomes
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ADVANTAGES
1. The vesicle suspension being water based offers greater
Patient Compliance over oil based systems.
2. Since the structure of the Niosome offers place to
accommodate hydrophilic, lipophilic as well as
amphiphilic drug moieties, they can be used for a
variety of drugs.
3. The characteristics such as size, lamellarity etc. of the
vesicle can be varied depending on the requirement.
4. The vesicles can act as a Depot to release the drug
slowly and offer a controlled release.
5. Due to their ability to entrap both hydrophobic and
hydrophilic drugs, niosomes are reported as ideal
carriers for the delivery of drugs such as doxorubicin,
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vaccines, insulin, siRNA and so on.
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6. For nano-vesicle-based delivery systems, niosomes can
be used as an alternative to liposomes and
polymersomes for chemical drug delivery.
7. They can also provide a way for the co-delivery of two
different kinds of drugs to achieve the desired
therapeutic effects. As with liposomes and
polymersomes, niosomes have some advantages such as
biocompatibility, low toxicity, biodegradability, etc.
8. Niosomes may serve as good carriers for the delivery of
various Protein And Peptide Drugs, and also show
good performance in vaccine formulation and
application.
9. Niosomes have been widely used as Oligonucleotide
Carriers for the treatment of many kinds of diseases in
reported studies. They can be used for the Delivery Of
Gene Materials due to some advantages such as good
chemical and physical stability, relatively smaller sizes, 6
etc.
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DISADVANTAGES
• Physical instability
• Aggregation
• Fusion
• Leaking of entrapped drug
• Hydrolysis of encapsulated drugs which limiting the shelf
life of the dispersion.
COMPOSITIONS
• The major components used for the preparation of
Niosomes are,
1. Non-ionic surfactants
2. Cholesterol
3. Drug
4. Ionic amphiphiles 7
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1. Non ionic surfactant- are the main ingredient, rather
than phospholipid. Non-ionic surfactants used in the
niosomes are amphipathic, including terpenoids,
polysorbates, Spans, alkyl oxyethylenes etc.
2. Cholestrol- The proper amount of cholesterol is added
to the niosomes to achieve the most stable formulation
due to its interaction with non-ionic surfactants . It
plays the role of regulating the structure and flexibility
of the membrane as a dependable buffer.
3. Drug- Both hydrophilic and hydrophobic drugs, can be
encapsulated in the niosomes.
4. Ionic amphiphiles -used in the niosomes for three
purposes: loading drugs, increasing the efficacy and
enhancing stability
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PREPARATION METHODS OF NIOSOMES
A. Ether injection method
B. Hand shaking method (thin film hydration technique)
C. Sonication Method
D. Micro fluidization method
E. Multiple membrane extrusion method
F. Reverse phase evaporation technique (REV)
G. Trans membranes pH gradient (inside acidic) Drug upake
Process: or remote loading technique
A. Formation of Niosomes from Proniosomes
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A. Ether injection method
Preparation steps:
Surfactant is dissolved in diethyl ether
↓
Then injected in warm water maintained at 60°C through a
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gauze needle
↓
Ether is vaporized to form single layered Niosomes.
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Figure 2. Ether injection method
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B. Hand shaking method (thin film hydration
technique)
Preparation steps:
Surfactant + cholesterol + solvent
↓
Remove organic solvent at Room temperature
↓
Thin layer formed on the Walls of flask
↓
Film can be rehydrated to form multilamellar Niosomes.
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Figure 3. Hand shaking method 13
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C. Sonication Method
Preparation steps
Drug in buffer + surfactant/cholesterol in 10 ml
↓
Above mixture is sonicated for 3 min at 60°C using
titanium
probe yielding niosomes.
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• This is also a suitable way to control the particle sizes of
the niosomes.
• Sonication can decrease the diameters of niosomes with
narrow size distribution.
• But probe sonication involves the use of high levels of
energy, and may cause a sudden increase of temperature
and the shedding of titanium
D. Micro fluidization Method
• It is a new method for formulation of niosome it is based
on jet principle
• i.e., by mixing two kinds of fluids such as alcohol and
water in microchannels
.
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Preparation steps
Two kinds of fluid in ultra high speed jets inside interaction
chamber
↓
Impingement of thin layer of Liquid in micro channels
↓
Formation of uniform Niosomes
• Niosomes can be formulated with the desired particle sizes
and size distribution by optimizing the parameters, such as
mixing conditions, surfactants and other materials
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E. Multiple membrane extrusion method
• Mixture of surfactant, cholesterol and diethyl phosphate in
chloroform is made into thin film by evaporation.
• The film is hydrated with aqueous drug solution.
• Resultant suspension is extruded through polycarbonate
membranes which are placed in series upto 8 passages
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F. Reverse Phase Evaporation Technique (REV)
Cholesterol + surfactant dissolved in ether + chloroform
↓
Sonicated at 5°c and again Sonicated after adding PBS
↓
Drug in aqueous phase is added to above mixture
↓
Viscous Niosomes suspension is diluted with PBS
↓
Organic phase is removed at 40°C at low pressure
↓
Heated on a water bath for 60°C for 10 mins to yield Niosomes.
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FORMATION OF NIOSOMES FROM PRONIOSOMES
• Proniosomes, also called dry niosomes, are dry-form
formulations of the non-ionic surfactant vesicles which
can be converted into niosomes after hydration in a short
time, and are now widely used in the formulation of
niosomes due to their good stability.
• Proniosomes consist of a water-soluble carrier coated
with non-ionic surfactants, and are easily hydrated into
niosomes before usage.
• Possesses several advantages such as good physical
and chemical stability for long-term storage, convenience
for transportation, and ease to scale up.
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Formation of niosomes from proniosomes
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CONCLUSION
Niosomes may function as a good nano-vesicle
delivery platform and provide a promising method for the
delivery of chemical drugs, protein drugs and gene
materials for the purpose of disease prevention and
treatment.
Compared with liposomes, they have some
advantages, such as good chemical and physical stability,
low cost and easy formulation.
More work need to be undertaken in the field to yield
more information for niosome development.
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AQUASOMES
DEFINITION
• Aquasomes are nanoparticulate carrier system but instead
of being simple nanoparticle these are three layered self
assembled structures.
• This three layered system contains a Core coated with
Polyhydroxy oligomer upon which Biochemically
active molecules are adsorbed.
• Ceramics are mainly used as core material because of
high degree of order and structural regularity.
• Polyhydroxy oligomer coating provides water like
environment & protect biochemically active molecule
from dehydration. 24
• Particle size lower than 1000 nm.
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METHOD OF PREPARATION OF AQUASOMES
3steps.
• I – Formation of an inorganic core
• II – Coating of the core with polyhydroxy oligomer
• III- Loading of the drug of choice to this assembly
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I. Formation of an inorganic core
Core preparation
• Preparation technique of core depends on the type of core to be
used.
• Generally nanocrystalline tin oxide, carbon ceramic
(diamond), calcium phosphate, hydroxyapatite are used as
core. Among these materials nanocrystalline calcium
phosphate and hydroxyapatite are widely used as core material
for aquasomes.
Types:
a) Synthesis of nanocrystalline tin oxide core ceramic
b) Self assembled nano crystalline brushite (calcium phosphate
dihydrate)
c) Nanocrystalline carbon ceramic, diamond particles 26
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a)Synthesis of nanocrystalline tin oxide core ceramic
• It can be synthesized by direct current reactive magnetron
sputtering.
• It is a high rate vacuum coating technique that allows the
deposition of many types of materials including metals ceramic
onto as many types of substrate materials by the use of
specially formed magnetic applied to a diode sputtering target.
• here, a 3 inches diameter target of high purity tin is sputtered in
a high pressure gas mixture of argon and oxygen.
• The ultrafine particles formed in the gas phase are then
collected on copper tubes cooled to 77K with flowing nitrogen.
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b)Self assembled nanocrystalline brushite (calcium
phosphate dihydrate)
• These can be prepared by colloidal precipitation and
sonication by reacting solution of disodium hydrogen
phosphate and calcium chloride.
c) Nanocrystalline carbon ceramic, diamond particles
• These can also be used for the core synthesis after ultra
cleansing and sonication.
• The equation for the reaction is as follows:
2 Na2HPO4 + 3 CaCl2 + H2O → Ca3(PO4) 2 + 4 NaCl + 2
H2 + Cl2 + (O) 28
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II. Coating of the core with Polyhydroxy Oligomer
• In the second step, ceramic cores are coated with carbohydrate
(Polyhydroxyl Oligomer).
• The coating is carried out by addition of carbohydrate into an
aqueous dispersion of the core under Sonication.
• These are then subjected to Lyophilization to promote an
irreversible adsorption of carbohydrate onto the ceramic
surface.
• The unadsorbed carbohydrate is removed by centrifugation.
• The commonly used coating materials are Cellobiose, citrate,
pyridoxal-5- phosphate, Trehalose and sucrose.
• Core to coat ratio of 1:4 or 1:5 caused formation of spherical
coated particles. 29
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III. Loading of the drug of choice to this assembly
• The final stage involves the loading of drug to the coated
particles by adsorption.
• For that, a solution of known concentration of drug is prepared
in suitable pH buffer, and coated particles are dispersed into it.
• The dispersion is then either incubated at low temperature for
drug loading or lyophilized after some time so as to obtain the
drug-loaded formulation (i.e., aquasomes).
• The preparation thus obtained is then characterized using
various techniques.
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APPLICATIONS OF AQUASOMES
1. Insulin delivery
2. Oral delivery of acid labile enzyme
3. As oxygen carrier
4. Antigen delivery
5. Delivery of drug
6. For delivery of gene
7. For delivery of enzymes
8. Miscellaneous
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1. Insulin Delivery
• Prepared aquasomes using a calcium phosphate ceramic
core for the parenteral delivery of insulin.
• The core was coated with various disaccharides such as
cellobiose, trehalose, and pyridoxal-5-phosphate.
• Subsequently the drug was loaded to these particles by
adsorption method.
• Prolonged reduction of blood glucose was observed
with all formulations except cellobiose-coated particles.
• Pyridoxal-5-phosphate coated particles were found to be
more effective in reducing blood glucose levels than
aquasomes coated with trehalose or cellobiose. 32
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2. Oral delivery of acid labile enzyme
• The use of a nanosized ceramic core–based system for
oral administration of the acid-labile enzyme
serratiopeptidase.
• The nano core was prepared by colloidal precipitation
under sonication at room temperature.
• The core was then coated with chitosan under constant
stirring, after which the enzyme was adsorbed over it.
• The enzyme was protected by further encapsulating the
enzyme-loaded core into alginate gel.
• These aquasomes were found to be protecting the
structural integrity of enzymes so as to obtain a better 33
therapeutic effect
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3. As oxygen carrier
• Prepared hydroxyapatite ceramic cores by co-
precipitation and self-precipitation.
• These cores were coated with various sugars including
cellobiose, trehalose, maltose, and sucrose.
• Subsequently, hemoglobin was adsorbed over the coated
ceramic core, and the percentage drug loading was
estimated by the Benzidine method.
• The Oxygen carrying capacity of Aquasome formulation
was found to be similar to that of fresh blood 34
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4. Antigen delivery
• Vehicle for hepatitis B vaccine for effective
immunization.
• Hydroxyapatite core was coated with cellobiose, and
finally hepatitis B surface antigen was adsorbed over the
coated core.
• The antigen-loading efficiency of plain hydroxyapatite
core (without cellobiose coating) was found to be
approximately 50%.
• whereas the coated core was observed to load 35
approximately 21% antigen.
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5. Delivery of drug
• Prepared Aquasomes loaded with Indomethacin through
the formation of an inorganic core of calcium phosphate
covered with a lactose film and further adsorption of
Indomethacin as a low-solubility drug.
• SEM and TEM techniques confirmed the spherical shape
of Aquasomes.
• However, results of drug(Indomethacin) release studies
from these carriers are yet to be determined.
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6. For delivery of gene
• Delivery system loaded with genetic material.
• Studies reveal that Aquasomes protect and maintain
structural integrity of the gene segment.
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Figure 8. Gene delivery through aquasomes
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7. For Delivery of Enzymes
• For delivery of enzymes like DNAse and pigment/dyes
because enzymes activity fluctuates with molecular
conformation and cosmetic properties of pigment are
sensitive to molecular conformation.
• DNAse a therapeutic enzyme used in the treatment of
cystic fibrosis was successfully immobilized on
Aquasomes and targeted to the specific site and elicited
significant therapeutic effect as desirable.
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8. Miscellaneous
• Prepared spherical porous hydroxyapatite particles by
spray-drying.
• These particles were tried as a carrier for the delivery of
drugs such as interferon α (IFN α), testosterone
enanthate, and cyclosporine A.
• The spherical porous hydroxyapatite particles were
shown to be useful as a biodegradable and
subcutaneously injectable drug carrier.
• The reinforcement of spherical porous hydroxyapatite
particles was suggested to be very effective for sustained
release of drugs
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CONCLUSION
Various research works on aquasomes indicated that
it can be used as successful nanoparticulate drug carrier.
Research works suggested antigen, insulin, hemoglobin,
vaccine can be delivered through aquasomes.
It helps in delivering conformationally sensitive
molecule to the site of action. Also aquasomes helps in
delivering protein molecule by preventing destructive
denaturation.
Though it has many advantages to be used as drug
carrier, extensive researches are yet required to study the
effect on in-vivo system, to identify if it has any toxic effect
in certain conditions and to prove its safety & efficacy in
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human body.
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PHYTOSOMES
• The term ‘Phyto’ means plant while ‘Some’ means cell-
like.
• Phytosome is a vesicular drug delivery system in which
phytoconstituents of herbal extract surround and bound
by lipids (one phyto-constituent molecule linked with at
least one phospholipid molecule).
• Phytosome protect valuable component of herbal extract
from destruction by digestive secretion and gut bacteria
and because of which they shows better absorption which
produces better bioavailability and improved
pharmacological and pharmacokinetic parameters
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than conventional herbal extract.
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MECHANISM OF PHYTOSOME TECHNOLOGY:
• Phytosomes results from the reaction of a
stoichiometric amount of the phospholipid
(phosphatidylcholine) with the standardized extract or
polyphenolic constituents (like simple flavonoids) in an
aprotic solvent.
• Phosphatidylcholine- bifunctional compound, the
phosphatidyl moiety is lipophilic and the choline moiety
is hydrophilic in nature.
• Choline head of the phosphatidylcholine molecule
binds to these compounds while the lipid soluble
phosphatidyl portion comprising the body which then
envelopes the choline bound material.
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PHYTOSOMES LIPOSOMES
1. Active chemical 1. Active principle is
constituents are anchored dissolved in the medium
through chemical bonds of the cavity or in layers
to the polar head of the of the membrane. No
phospholipids. chemical bond is formed.
2. The phosphotidylcholine 2. Here hundreds and
and the individual plant thousands of
compound form a 1:1 or phosphotidylcholine
2:1 complex depending molecules suround the
on the substance. water soluble molecule.
3. The phytosome is a unit 3. liposome is an aggregate
of a few molecules of many phospholipid
bonded together. molecules that can
enclose other phytoactive
molecules. 43
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How does “Phytosome” differ from a “Liposome” ?
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Main difference between liposome and phytosome
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ADVANTAGES OF PHYTOSOME
• Phytosome is much better absorbed than liposome
because drug is in complex form with lipid.
• Leakage of drug during storage does not occur in
phytosome, because drug is bonded with lipid, however loss
may occur due to some chemical degradation i.e. hydrolysis.
• Phosphatidylcholine used in preparation of phytosomes,
besides acting as carrier also act as a hepatoprotective.
• The physiochemical stability of phytosome depends
upon the physicochemical properties of drug-lipid complex.
• Application of phytpconstituent in form of phytosome
improve their percutaneous absorption and as functional 45
cosmetics.
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PREPARATION OF PHYTOSOMES:
1. Active constituent of herbal extract+ Phospholipid is
mixed in aprotic solvent for complex formation with
constant stirring.
2. Complex is isolated with addition of non solvent
Complex in drying form
3. Complex dissolve in organic solvent
4. Drying
5. Thin Film Formation
6. Hydration of thin film
7. Formation of phytosome complex (suspension)
8. Isolation by precipitation with non solvent (such as
aliphatic hydrocarbons)
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9. Drying (By lyophilization or spray drying)
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APPLICATIONS OF PHYTOSOME
• The novel form of herbal products phytosomes are better
absorbed than conventional herbal extracts.
• This was observed in SILIPHOSTM (Silybin
phytosome). Silybin is chief component of Silymarin,
valued for its ability to protect and restore liver
activities.
• Phytosomes serve as a delivery system consisting of
microscopic vesicles that improve the potential
bioavailability, as can be observed in skin care or 47
nutritional products.
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• Phytosome are supposed to increase the systemic
bioavailability of the hydrophilic phytoconstituents and there
by increases their therapeutic efficacy.
• Grape Seed Phytosome: 50 to 100 mg Systemic antioxidant,
Best choice for most people under age of fifty. Also specific
for the eyes, lungs, diabetes, varicose veins, and protection
against heart disease.
• Green Tea Phytosome: 50 to 100 mg Systemic antioxidant.
Several studies have suggested that the flavonoids and caffeine
in green tea can help elevate metabolic rate,
increase fat oxidation and even improve insulin activity. 48
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• Ginkgo Biloba Phytosome: 120 mg Best choice for most
people over the age of 50. Protects brain and vascular lining
• Hawthorn Phytosome: 100 mg Best choice in heart disease
or high blood pressure.
• Leucoselect Phytosome: 50-100 mg Best choice for
antioxidant support, cardiovascular system.
• Curcumin phytosome: Powerful free radical scavenger, can
help to support a balanced immune system response to normal
metabolic stress, and can promote healthy joint mobility and
flexibility.
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CONCLUSION:
• Phytosomes are novel formulations which offer
improved bioavailability of hydrophilic favonoids and
other similar compounds through the skin or
gastrointestinal tract.
• They have many distinctive advantages over other
conventional herbal formulations. The formulation
methodology for phytosome is simple and can be easily
upgraded to a commercial scale.
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ELECTROSOMES
BIOFUEL CELLS
Biofuel cells are electrochemical devices that use
enzymatic reactions to catalyze the conversion of chemical
energy to electricity in a fuel cell.
• They can be classified as microbial fuel cells (MFCs),
which use living microorganisms or enzymatic fuel cells,
which use purified enzymes.
• Hybrid biofuel cells combine the characteristics of both
classes of biofuel cells.
• This concept was initially introduced by the use of redox
enzymes surface-displayed on different microorganisms 51
and in biofuel cells
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ELECTROSOME
• Is a novel surface-display system based on the specific
interaction between the cellulosomal scaffoldin protein
and a cascade of redox enzymes that allows multiple
electron release by fuel oxidation.
• The electrosome is composed of two compartments:
(i) Hybrid Anode, which consists of dockerin-containing
enzymes attached specifically to cohesin sites in the
scaffoldin to assemble an ethanol oxidation cascade, and
(ii) Hybrid Cathode, which consists of a dockerin-
containing oxygen-reducing enzyme attached in multiple
copies to the cohesin-bearing scaffoldin
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REFERENCE
1. Xuemei Ge, Minyan Wei, Suna He and Wei-En Yuan,
Advances of Non-Ionic Surfactant Vesicles (Niosomes)
and their application in Drug Delivery, Journal of
Pharmaceutics. 2019;Vol 11(15): Pg no. 1-16.
2. S.P Vyas, R.K.Khar, Targeted and Controlled Drug
Delivery Novel Carrier Systems, CBS Publishers and
Distributors. Pg no. 249-259.
3. Sritoma Banerjee, Kalyan Kumar Sen, Aquasomes: A
novel nanoparticulate drug carrier, Journal of Drug
Delivery Science and technology. 2018; Vol 43: Pg no.
446-452.
4. M.Sravanthi and J.Shiva Krishna, Phytosomes : A novel
Drug Delivery for Herbal Extracts, International Journal
of Pharmaceutical Sciences and Research. 2013; Vol.4(3): 53
Pg no. 949-959.
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5. Alon Szczupak , Dror Aizik , Sarah Morais , Yael
Vazana, Yoav Barak, Edward A. Bayer et al., The
Electrosome: A Surface-Displayed Enzymatic Cascade
in a Biofuel Cell’s Anode and a High-Density Surface-
Displayed Biocathodic Enzyme, Journal of
Nanomaterials. 2017; Vol 7(153) Pg 1-17.
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THANK YOU
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