NIOSOMESNIOSOMES

INTRODUCTION:INTRODUCTION:

• Niosomes are novel drug delivery systems in which medication is encapsulated in a vesicle.

• Niosomes are non-ionic surfactant based uni or multilamellar vesicles in which an aqueous solute is entirely enclosed by a membrane which is formed by surfactant macromolecules as bilayers.

• They are very small and microscopic in size. Their size lies in nanometric scale.

• A diverse range of materials have been used to form niosomes such as alkyl ethers, alkyl esters, amides, fatty acids and amino acid compounds.

• They are vesicular systems similar to liposomes in which bilayer is made up of phospholipids and they can be used as carriers of amphiphilic and lipophilic drugs

• The niosome is made of a surfactant bilayer with its hydrophilic ends exposed on the outside and inside of the vesicle, while the hydrophobic chains face each other within the bilayer.

Hydrophobic chains

Hydrophilic cavity

• Cholesterol when incorporated in bilayer, alters the bilayer characteristics.

ADVANTAGES:

High patient compliance.

Osmotically active and stable, as well as they increase the stability of entrapped drug.

The vesicles can act as a depot to release the drug slowly and offer a controlled release.

Can increase the oral bioavailability of drugs

Can enhance the skin penetration of drugs

The surfactants are biodegradable, biocompatible, and non-immunogenic.

DISADVANTAGES:

Physical instability

Aggregation

Fusion

Leaking of entrapped drug

Hydrolysis of encapsulated drugs which limits the shelf life of the

dispersion.

COMPARISON OF NIOSOMES Vs LIPOSOMES

Niosomes has certain advantages over liposomes. Liposomes face problems such as – they are expensive, their

ingredients like phospholipids are chemically unstable due to their predisposition to oxidative degradation, they require special storage and handling and purity of natural phospholipids is variable.

Niosomes do not have any of these problems as they are made of uncharged single-chain surfactant molecules compared to liposomes.

Niosomes behave in-vivo like liposomes, prolonging the circulation of entrapped drug and altering its organ distribution and metabolic stability.

Like liposomes, the properties of niosomes depends both on the composition of the bilayer and method of their production.

TYPES OF NIOSOMESTYPES OF NIOSOMES

Based on the vesicle size, niosomes are divided into 3 groups-

Small Unilamellar vesicles (SUV, size 0.025-0.05 μm)

Multilamellar vesicles(MLV, size > 0.05 μm)

Large Unilamellar vesicles (MUV, size > 0.1 μm)

METHODS OF PREPARATION

Preparation of Small unilamellar vesicles

Preparation of Multilamellar vesicles

Preparation of Large unilamellar vesicles

Miscellaneous

PREPARATION OF SUVs:

SONICATION:

• In this aliquot of drug solution in buffer is added to 150 μmol of surfactant/cholesterol mixture in a 10ml glass vial.

• The mixture is probe sonicated at 60°C for 3 minutes using a sonicator with a titanium probe to yield niosomes.

• Probe sonicator- when the sample volume is small.

• Bath sonicator- when the sample volume is large.

• Care must be taken while working with temperature sensitive solute.

PREPARATION OF MLVs:

HAND SHAKING METHOD (Thin film hydration technique):

• The surfactant and cholesterol mixture is dissolved in 10 ml of volatile organic solvent (diethyl ether, chloroform or methanol) in a round bottom flask.

• The organic solvent is evaporated at room temperature (20°C) using rotary evaporator leaving a thin layer of solid mixture deposited on the wall of the flask.

• The dried surfactant film can be rehydrated with aqueous phase at 0-60°C by gentle agitation.

PREPARATION OF LUVs:

REVERSE PHASE EVAPORATION:

• Surfactant is dissolved in chloroform and emulsified with 0.25 vol of phosphate saline buffer to get a W/O emulsion.

• The mixture is then sonicated and subsequently chloroform is evaporated under reduced pressure.

• The lipid or surfactant forms a gel first and subsequently hydrates to form vesicles.

• Free drug (unentrapped) is generally removed by dialysis.

ETHER INJECTION:

• In this, slow injection of surfactant:cholesterol solution in ether (20ml) through a 14 gauge needle at approximately 0.25 ml/min into a pre-heated aqueous phase maintained at 60°C.

• This forms large vesicles due to vaporization of solvent resulting in ether gradient extending towards the ether-water interface. It results in the formation of a bilayer sheet, which eventually folds on itself to form sealed vesicles.

• In case of thermo labile drugs, fluorinated hydrocarbons are used incase of ether.

MISCELLANEOUS:

MULTIPLE MEMBRANE EXTRUSION METHOD:

• Mixture of surfactant, cholesterol and dicetyl phosphate in chloroform is made into thin film by evaporation.

• The film is hydrated with aqueous drug solution and the resultant suspension extruded through polycarbonate membranes, which are placed in series upto 8 passages.

• It is a good method for controlling niosome size.

BUBBLE METHOD:

• It is a novel technique for the 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 are positioned in the first and second neck and nitrogen supply through the third neck.

• Cholesterol and surfactant are dispersed together in this buffer (pH 7.4) at 70°C, the dispersion mixed for 15 seconds with high shear homogenizer and immediately “bubbled” at 70°C using nitrogen gas.

FORMATION FROM PRONIOSOMES:

• To create proniosomes, a water soluble carrier such as sorbitol is first coated with the surfactant.

• The coating is done by preparing a solution of the surfactant and cholesterol in a volatile organic solvent, which is sprayed onto the powder of sorbitol kept in a rotary evaporator.

• The evaporation of the organic solvent yields a thin coat on the sorbitol particles.

• The niosomes can be prepared from the proniosomes by adding the aqueous phase with the drug to the proniosomes with brief agitation at a temperature greater than the mean transition phase temperature of the surfactant.

SEPARATION OF FREE DRUG

The removal of unentrapped solute from vesicles include various techniques like –

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 from niosomal dispersion through a Sephadex-G-50 column and eluted with phosphate buffered saline or normal saline.

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

CHARACTERIZATION OF NIOSOMESCHARACTERIZATION OF NIOSOMES

SIZE, SHAPE AND MORPHOLOGY:

• Freeze Fracture Electron Microscopy - visualizes the vesicular structure of surfactant based vesicles.

• Photon Correlation spectroscopy, Ultracentrifugation - determine mean diameter of the vesicles.

• Electron Microscopy - morphological studies of vesicles.

• Freeze thawing - keeping vesicle suspension at -20°C for 24 hrs and then heating to ambient temperature increases the vesicle diameter, which result in fusion of vesicles during the cycle.

VESICULAR SURFACE CHARGE:

• It is determined by measuring the electrophoretic mobility and is expressed in terms of Zeta potential.

ENTRAPMENT EFFICIENCY: After preparing niosomal dispersion, unentrapped drug is separated

by dialysis and the entrapped drug in niosomes is determined by complete vesicle disruption using 50% n-propanol or 0.1% Triton X-100 and the resultant solution is analysed by appropriate assay method for the drug.

IN VITRO STUDIES: A method of in vitro release study includes the use of dialysis

tubing. A dialysis sac is washed and soaked in distilled water. The vesicle suspension is pipetted into a bag made up of the tubing and is sealed. The bag containing the vesicles is placed in 200 ml buffer solution in a 250 ml beaker with constant shaking at 25°C or 37°C. At various time intervals, the buffer is analyzed for the drug content by an appropriate assay method.

APPLICATIONS

In the treatment of Lieshmaniasis:

Niosomes are used for drug targeting in treatment of diseases in which the organism resides in the RES. Lieshmaniasis is a disease in which parasite invades the cells of liver and spleen. Niosomes are used for the delivery of stilbogluconate, an anti-leishmaniasis agent to visceral organs.

In Oncology:

Various anticancer drugs like MTX, DOX can be encapsulated inside the niosomes and they can be easily delivered to the tumor cells due to small size.

As a carrier for Haemoglobin In the delivery of peptide drugs

As immunological adjuvants: The ability of niosomes to enhance antibody production in

response to Bovine Serum Albumin (BSA)was compared with Freund’s complete adjuvant in the BALB/c mouse which revealed niosomes as potent stimulator of cellular immunity.

In transdermal drug delivery:

They have application in topical and transdermal products both containing hydrophobic and hydrophilic drugs. An increase in the penetration rate is achieved by transdermal delivery incorporated in niosomes. The intracellular route is the main route of vesicle penetration across the skin. Ex: erythromycin

In diagnostic imaging:

Niosomes can act as carriers for radiopharmaceuticals and site specific vehicles for spleen and liver imaging.

REFERENCES

Vyas S.P. , Khar R.K. ,Targeted & Controlled Drug Delivery, Novel Carrier Systems, CBS Publication,2002,Page No.249-276.

Malhotra M. and Jain N.K. Niosomes as Drug Carriers.,Indian Drugs 1994, Page No: 81-86.

www.pharmainfo.netwww.sciencedirect.comwww.pharmatutor.org

Thank you