Niosomes

Niosomes

(Targeted drug delivery systems)

Niosomes

•       Medication is  encapsulated in a  vesicle

•       Composed of a bilayer  of non-ionic surface  active agents

•       They are vesicles composed of non-ionic surfactants

•       Biodegradable, relatively nontoxic, more stable and  inexpensive

•       Used as an alternative to liposomes

Advantages of niosomes

•       These are very small in size -nanometric scale

•       Structurally similar to liposomes, but offer several advantages over them

•       Niosomes greatly increase transdermal drug delivery and  also in targeted drug delivery

•       Hydrophilic, lipophilic and amphiphilic drugs can be accommodated in the vesicular moieties

•       Act as a depot to release the drug slowly and offer a controlled release

•       Increase the stability of the entrapped drug

•       Handling and storage of                surfactants do not require any special conditions

•       Enhance the skin penetration of drugs

Structure of niosomes

Ø  Niosomes are microscopic  lamellar structures

Ø  Formed on the admixture of  non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class and cholesterol with subsequent hydration in aqueous media

•          Niosomes may be unilamellar or multilamellar depending  on the method used to prepare them

•          The hydrophilic ends are exposed on the outside and inside  of the vesicle, while the hydrophobic chains face each  other within the bilayer

Methods of preparation

1. Ether injection method
2. Film hydration method
3. Reverse phase evaporation
4. The “Bubble” method
5. Micro fluidization
6. Sonication

1. Ether injection method

•       In this method a solution of niosomal ingredients in ether is  slowly injected into an aqueous medium at high  temperature

•       A mixture of surfactant and cholesterol (150 μmol) is  dissolved in ether (20 ml)

•       Injected into an aqueous phase (4 ml) using a 14- gauge  needle syringe at the rate of approximately 0.25ml/min

•       The aqueous phase is preheated to 60⁰C during the injection  of the ether solution

•       This causes evaporation of ether leading to the formation of  single layered vesicles

•       The particle size of niosomes formed can range b/w 50μm  and 1000μm

Advantage

•      Niosomes prepared by ether injection method have better  entrapment efficiency than those prepared by the film or  sonication

Disadvantage

•      Small amount of residual ether  frequently remains in the  final product and is difficult to remove

2. Film hydration method

•          Vesicle-forming agents such as the surfactant and cholesterol are dissolved in a volatile organic solvent such  as diethyl ether, chloroform, or methanol in a round bottom  flask

•          The organic solvent is evaporated under reduced pressure  using a rotary evaporator

•          A thin film of solid mixture remains deposited on the walls of the flask

•          The dried surfactant layer is rehydrated with the aqueous  phase at normal temperature with gentle agitation to yield  unilamellar niosomes or smaller niosomes using sonication,  technique

3. Reverse phase evaporation technique

•          In this method, cholesterol and surfactant (1:1 ratio) are  dissolved in a mixture of ether and chloroform

•          An aqueous phase containing the drug to be loaded is added to this

•          Mixture is sonicated at 4⁰C- 5⁰C until a clear gel is formed

•          Phosphate buffered saline (PBS) is added to it Sonicated

•          The temperature is raised to 40⁰C and the organic phase is  removed under reduced pressure

•          A viscous niosome suspension is obtained

•          Diluted with PBS and heated on a water bath at 60⁰C for  10min to yield niosomes

4. The Bubble method

•          This method allows the preparation of niosomes without the use of organic solvent

•          The niosomes are prepared in a bubbling unit, which consists of a round bottom flask with three necks

•          The flask is positioned in a water temperature

•          In the first neck water – cooled reflux is positioned

•          In the second neck thermometer is fixed

•          The third neck is used to bubble nitrogen gas into the mixture

•          A dispersion of cholesterol and surfactant in a buffer (pH 7.4) is  taken in the flask and maintained at 70⁰C

•          The dispersion is then mixed with shear homogenizer

•          Nitrogen gas is immediately bubbled into it at 70⁰C to yield  niosomes

5. Sonication

•          The aqueous phase is added into the mixture of  surfactant and cholesterol in a scintillation vial

•          Homogenized using a sonic probe

•          The resultant vesicles are of small unilamellar (SUV) type  niosomes

•          The SUV type niosomes are larger than SUV liposomes

6. Micro fluidization

•          This is a recent technique to prepare small MLVS

•         A microfludizer is used to pump the fluid at a very high  pressure (10,000 psi) through a 5 mm screen

•          It is then forced along defined micro channels, which direct  two streams of fluid to collide together at right angles,  there by affecting a very efficient transfer of energy

•          The lipids/surfactants can be introduced  fluidizer

•          The fluid collected can be recycled until vesicles are obtained

Separation of free/unentrapped drug

Dialysis

The aqueous niosomal dispersion is dialyzed in a dialysis tubing against phosphate buffer or normal saline or glucose solution.

Gel Filtration

The unentrapped drug is removed by gel filtration of niosomal dispersion through a Sephadex-G-50 column and elution with phosphate buffered saline or normal saline.

Centrifugation

The niosomal suspension is centrifuged and the supernatant is separated. The pellet is washed and then resuspended to obtain a niosomal suspension free from unentrapped drug

Evaluation of niosomes

1. Entrappment efficiency

Entrapment efficiency = Amount entrapped / Total amount added x 10

2. Vesicle Size

Laser Light Scattering method

3. Particle size analysis

Scanning Electron Microscopy (SEM)

4. Bilayer formation

Polarised Light Microscope

5. Number of lamellae

Nuclear Magnetic Resonance (NMR) spectroscopy

6.In vitro Release Study

7. In vivo Release Study

Scanning Electron Microscopy

Polarised Light Microscope

Applications

•          Anti-neoplastic treatment

•          Treatment of Leishmaniasis

•          Delivery of peptide drugs

•          Used in studying immune response

•          Niosomes as carriers for haemoglobin

•          Transdermal drug delivery systems

Summary

1. Niosomes are vesicular systems in which the medication is encapsulated in a vesicle composed of a bilayer of non-ionic  surface active agents

2.       The methods of preparation include Ether injection method, Film hydration method, Reverse phase evaporation, The  “Bubble” method, Micro fluidization, Sonication

3.       Niosomes can be characterized for Entrapment efficiency, Vesicle Size, Particle size, Bilayer formation, Number of  lamellae, In vitro and In vivo release study

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