NIOSOMES AQUASOMES LIPOSOMES

1. Niosomes, Aquasomes, Phytosomes,
Electrosomes
Prepared by : Shubhrat Maheshwari
M.Pharma 1st year [2nd semester]
Pharmaceutics
Molecular pharmaceutics (MPH 201T)
SRMS College of Engineering & Technology
Bareilly

2. CONTENTS
 Niosomes
 Aquasomes
 Phytosomes
 Electrosomes

3. Niosomes
 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. Although structurally similar to liposomes, they offer
several advantages over them.
 Niosomes have recently been shown to greatly increase transdermal drug delivery and also
can be used in targeted drug delivery, and thus increased study in these structures can provide
new methods for drug delivery.

4. Structure of Niosomes
• Structurally, niosomes are similar to liposomes, in that they are also made up of a
bilayer.
• However, the bilayer in the case of niosomes is made up of non-ionic surface active
agents rather than phospholipids as seen in the case of liposomes.
• Most surface active agents when immersed in water yield micellar structures however
some surfactants can yield bilayer vesicles which are niosomes.

5. Types of Niosomes
1) Multi lamellar vesicles (MLV)
2) Unilamellar vesicles (ULV)
ii) Large unilamellar vesicles (LUV)
iii) Small unilamellar vesicles (SUV)

6. Composition of Niosomes
• The two major components used for the preparation of niosomes are,
1. Cholesterol
2. Nonionic surfactants
1. Cholesterol
Cholesterol is used to provide rigidity and proper shape, conformation to the niosomes preparations.
2. Nonionic surfactants
• The role surfactants play a major role in the formation of niosomes.
• The following non-ionic surfactants are generally used for the preparation of niosomes.
• E.g.Spans (span 60, 40, 20, 80), Tweens (tween 20, 40, 60, 80), etc.
• The non ionic surfactants possess a hydrophilic head and a hydrophobic tail.

7. Method of preparation
• The preparation methods should be chosen according to the use of the niosomes, since the
preparation methods influence the number of bilayers, size, size distribution, and entrapment
efficiency of the aqueous phase and the membrane permeability of the vesicles.
A. Ether injection method
Surfactant + cholesterol is dissolved in diethyl ether
↓
Then injected in warm water maintained at 60°C through a 14
gauze needle
↓
Ether is vaporized to form single layered niosomes.

8. B. Hand shaking method (thin film hydration technique)
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
C. Sonication method
Drug in buffer +surfactant/cholesterol in 10 ml of aqueous phase
↓
Above mixture is sonicated for 3 minutes at 60°C using titanium
Probe yielding niosomes

9. D. Multiple membrane extrusion method
Mixture of surfactant, cholesterol in chloroform is made into thin film by evaporation.
↓
The film is hydrated with aqueous drug solution and the resultant suspension extruded through
polycarbonate membrane .
• It is a good method for controlling noisome size.
E. Reverse phase evaporation technique (REV)
Cholesterol + surfactant dissolved in ether + chloroform
↓
Sonicated at 50°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 minutes to yield niosomes.

10. F. The bubble method
It is novel technique for the one step preparation of liposomes and niosomes without the use of
organic solvents.
↓
The bubbling unit consists of round-bottomed flask with three necks positioned in water bath to
control the temperature.
↓
Water-cooled reflux and thermometer is positioned in the first and second neck and nitrogen
supply through the third neck.
↓
Cholesterol and surfactant are dispersed together in the buffer (pH 7.4) at 70°C, the dispersion
mixed for 15 seconds with high shear homogenizer and immediately afterwards “bubbled” at
70°C using nitrogen gas.

11. G. Trans membranes pH gradient (inside acidic) drug uptake process: or remote loading
technique
Surfactant + cholesterol in chloroform
↓
Solvent is evaporated under reduced pressure
↓
Thin film is deposited on the walls of RBF
↓
Hydrated with citric acid by vortex mixing
↓
3 cycles of freezing and thawing then sonication
↓
Addition of aqueous drug solution and vortexing
↓
pH raised to 7.0-7.2 by 1M disodium phosphate and heated at
60°c for 10 minutes so give niosomes

12. Application of Niosomes
 Drug Targetting
• One of the most useful aspects of niosomes is their ability to target drugs.
• Niosomes can be used to target drugs to the reticuloendothelial system.
• It can be achieved by coating with polymer e.g. PEG.
 In Diagnosis
• Niosomes have also been used as carriers for iobitridol, a diagnostic agent used for X-ray imaging.
 Anti-neoplastic Treatment
• Most antineoplastic drugs cause severe side effects.
• Niosomes can alter the metabolism; prolong circulation and half life of the drug, thus decreasing the
side effects of the drugs.
• Niosomes, is decreased rate of proliferation of tumor and higher plasma levels accompanied by
slower elimination.

13.  Leishmaniasis
• Leishmaniasis is a disease in which a parasite of the genus Leishmania invades the cells of the
liver and spleen.
• Use of niosomes in tests conducted showed that it was possible to administer higher levels of
the drug without the triggering of the side effects, and thus allowed greater efficacy in
treatment.
 Delivery of Peptide Drugs
• Oral peptide drug delivery has long been faced with a challenge of bypassing the enzymes
which would breakdown the peptide.
• Use of niosomes to successfully protect the peptides from gastrointestinal peptide
breakdown is being investigated.
• In an In-vitro study conducted by oral delivery of a vasopressin derivative entrapped in
niosomes showed that entrapment of the drug significantly increased the stability of the
peptide.

14.  Niosomes as Carriers for Haemoglobin
• Niosomes can be used as carriers for haemoglobin within the blood.
• The niosomal vesicle is permeable to oxygen and hence can act as a carrier for haemoglobin
in anaemic patients.
 To organs other than RES
• It has been suggested that carrier system can be directed to specific sites in the body by use
of antibodies.
• Immunoglobulins seem to bind quite readily to the lipid surface, thus offering a convenient
means for targeting of drug carrier.
• Many cells possess the intrinsic ability to recognize and bind particular carbohydrate
determinants and this can be exploited to direct carriers system to particular cells.

15. Aquasomes
• Aquasomes are nanoparticulate carrier system but instead of being simple nanoparticle these
are three layered self assembled structures.
• It comprised of a solid phase nanocrystalline core coated with oligomeric film on which
biochemically active molecules are adsorbed with or without modification.
• Aquasomes are like “bodies of water" and their water like properties protect and preserve
fragile biological molecules, and this property of maintaining conformational integrity as well
as high degree of surface exposure is exploited in targeting of bioactive molecules.
• These three layered structures are self-assembled by non covalent and ionic bonds. These
carbohydrate stabilize nanoparticles of ceramic are known as “aquasomes”.

16. Structure of Aquasomes

17. Method of preparation
• The method of preparation of aquasomes involves three steps.
• The general procedure consists of formation of an inorganic core, followed by Coating of the
core with polyhydroxy oligomer, and finally loading of the drug of choice to this assembly.

18. I- Formation of an inorganic core
• It involves the fabrication of a ceramic core, and the procedure depends upon the materials
selected.
• The two most commonly used ceramic cores are calcium phosphate and diamond.
a) Synthesis of nanocrystalline tin oxide core ceramic - It can be synthesized by direct current
reactive magnetron sputtering.
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.

19. 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 cores
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.
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 kept overnight at low temperature for drug loading or lyophilized
after some time so as to obtain the drug-loaded formulation (i.e., aquasomes).

20. Applications
 Insulin Delivery
• Aquasomes for pharmaceuticals delivery i.e. insulin, developed because drug activity is
conformationally specific.
• Bio activity preserved and activity increased to 60% as compared to i.v administration and
toxicity not reported.
 Oral Delivery of Enzyme
• Aquasomes also used for delivery of enzymes like DNAase and pigments/dyes because
enzymes activity fluctuates with molecular conformation and cosmetic properties of pigments
are sensitive to molecular conformation.

21.  Antigen Delivery
• The adjuvants generally used to enhance the immunity to antigens have a tendency either to
alter the conformation of the antigen through surface adsorption or to shield the functional
groups.
• So Kossovsky et al demonstrated the efficacy of a new organically modified ceramic antigen
delivery vehicle.
• These particles consisted of diamond substrate coated with a glassy carbohydrate (cellobiose)
film.
• These aquasomes provided conformational stabilization as well as a high degree of surface
exposure to protein antigen.
• Diamond, being a material with high surface energy, was the first choice for adsorption and
adhesion of cellobiose. It provided a colloidal surface capable of hydrogen bonding to the
proteinaceous antigen.

22.  As oxygen Carrier
• Aquasomes as red blood cell substitutes, haemoglobin immobilized on oligomer surface
because release of oxygen by haemoglobin is conformationally sensitive.
• By this toxicity is reduced, haemoglobin concentration of 80% achieved.

23. Phytosomes
• The term “phyto” means plant while “some” means cell-like.
• Phytosomes are little cell like structure.
• Phytosomes are novel drug delivery system containing bioactive phytoconstituents of herbs
surround and bound by phospholipids.
• Phytomedicines are complex chemical mixtures prepared from plants.
• Water soluble phytoconstituents (flavonoids) are poorly absorbed.

24. Physical properties
• It is lipophilic substance
• Freely soluble in nonpolar solvent
• Moderately soluble in fats
• Insoluble in water

25. Structure of phytosomes

26. Method of preparation
• Phytosomes are prepared by reacting natural or synthetic phospholipids with active
components like bioflavonoid, flavolignan and polyplenolic constituents.
• Solvents evaporation method is the most common technique used for the preparation of
phytosomes.

27. Common stage of preparation
Phospholipds
↓
Solution of phospholipid in organic solvents with drug extract
↓
Drying
↓
Formation of thin film
↓
Hydration
↓
Formation of phytosomal suspension

28. Advantages
• It enhances the absorption of lipid insoluble polar phytoconstituents through oral as well as
topical route showing better bioavailability, enhance significantly greater therapeutic benefit.
• As the absorption of active constituent is improved, its doses requirement is also reduced.
• Phytosomes are also superior to liposomes in skin care products.
• It assures proper delivery of drug to the respective tissues.

29. Application
• Enhancing bioavailability
• Antioxidant properties
• Hepato protective
• Transdermal application
• Cancer treatment

30. Electrosomes
• These are the transmembrane protein generate and propagate the electrical signals that allow
us to sense our surroundings, process, information, make decisions, and move.
• Ion channel proteins act as gates that span the lipid bilayer that surrounds all electrochemical
gradients.
• The ion flux through a channel pore can be extremely high.
• They are high resolution in function and 3D structure to description of their molecules.
• The high resolution structure of ion channel and ion channel associated protein are providing
the substrates for sophisticated tests of the mechanisms of channel gating and permeation.
• Ion perform two basic function open and close to control the passage of ion across the cell
membrane.

31. Structure

32. Structure of Electrosomes
• Ion channels are the part of large protein network. These networks includes cytoskeletal
components, signaling proteins like protein kinase and phosphatases, and channel-associated
proteins that recruit these signaling molecules to the channel to modify its function.

33. Applications
• Ear targeting
• Brain targeting
• Muscles targeting
• Nervous system targeting

34. Thanking
you…..