INTRODUCTION Niosomes are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids. They are vesicular systems similar to liposomes that can be used as carriers of hydrophilic and lipophilic drugsIt is less toxic and improves the therapeutic index of drug by restricting its action to target cells
Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle.The niosomes are very small, and microscopic in size. Their size lies in the nanometric scale.Niosomes are unilamellar or multilamellar vesicles.The vesicle is composed of a bilayer of non-ionic surface active agents and hence the name niosomes.A diverse range of 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.
Structure of NiosomesNiosomes are microscopic lamellar structures which are formed on the admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class and cholesterol with subsequent hydration in aqueous media.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.Niosomes may be unilamellar or multilamellar depending on the method used to prepare them.
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.Hence, the vesicle holds hydrophilic drugs within the space enclosed in the vesicle, while hydrophobic drugs are embedded within the bilayer itself.
The figure below will give a better idea of what a niosome looks like and where the drug is located within the vesicle ,
Comparison of Niosomes v/s Liposomes Liposomes Niosomes1) They are expensive. 1) They are not expensive.2) Ingredients like phospholipids are 2) Ingredients like Surfactant arechemically unstable. chemically stable.3)It require special storage and 3) Not require special storage andhandling . handling.4) liposomes are made from neutral or 4) Niosomes are made of unchargedcharged double chained phospholipids. single-chain surfactant molecules.5) liposomes increase the 5) Niosomes also increase thebioavailability of the drug and reduce bioavailability of the drug and reducethe clearance. the clearance. Niosomes can also be used for targeted drug delivery, similar to liposomes.
Advantages of Niosomes The vesicle suspension being water based offers greater patient compliance over oil based systems Since the structure of the niosome offers place to accommodate hydrophilic, lipophilic as well as ampiphilic drug moieties, they can be used for a variety of drugs. The characteristics such as size, lamellarity etc. of the vesicle can be varied depending on the requirement. The vesicles can act as a depot to release the drug slowly and of controlled release.Other advantages of niosomes are: They are osmotically active and stable. They increase the stability of the entrapped drug Handling and storage of surfactants do not require any special conditions Can increase the oral bioavailability of drugs
o Can enhance the skin penetration of drugso They can be used for oral, parenteral as well topical useo The surfactants are biodegradable, biocompatible, and non- immunogenico Improve the therapeutic performance of the drug by protecting it from the biological environment and restricting effects to target cells, thereby reducing the clearance of the drug.o The niosomal dispersions in an aqueous phase can be emulsified in a non-aqueous phase to control the release rate of the drug and administer normal vesicles in external non-aqueous phase.o High patient compliance in comparison with oily dosage forms.o Accommodate drug molecules with a wide range of solubilities.o Characteristics of the vesicle formulation are variable and controllableo Osmotically active and stable, as well as they increase the stability of entrapped drug.o Biodegradable, biocompatible and nonimmunogenic.
Method of PreparationA. Ether injection method• Introduce a solution of surfactant dissolved in diethyl ether into warm water maintained at 60°C.• Surfactant mixture in ether is injected through 14- gauge needle into an aqueous solution of material.B . Hand shaking method (Thin film hydration technique)• Surfactant and cholesterol are dissolved in a volatile organic solvent• Organic solvent is removed at room temperature using rotary evaporator leaving a thin layer of solid mixture deposited on the wall of the flask• Dried surfactant film can be rehydrated with aqueous phase at 0-60°C with gentle agitation
C . Sonication• Aliquot of drug solution in buffer is added to the surfactant/cholesterol mixture in a 10-ml glass vial• Mixture is probe sonicated at 60°C for 3 minutes using a sonicator with a titanium probe to yield niosomes.D. 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
E. Reverse Phase Evaporation Technique• Cholesterol and surfactant (1:1) are dissolved in a mixture of ether and chloroform.• An aqueous phase containing drug is added to this and the resulting two phases are sonicated at 4-5°C.• organic phase is removed at 40°C under low pressure• The resulting viscous niosome suspension is diluted with PBS and heated on a water bath at 60°C for 10 min to yield niosomes.F. Aqueous Dispersion Method• Microdispersion of aqs.media containing solute for encapsulation• Controlled temp. and agitation provides vesicles
Table 1: Drugs incorporated into niosomes byvarious methods Method of Drug incorporated preparation Ether Injection Sodium stibogluconate Doxorubicin Hand Shaking Methotrexate Doxorubicin Sonication 9-desglycinamide 8-arginine Vasopressin Oestradiol
Separation of Unentrapped Drug1. Dialysis The aqueous niosomal dispersion is dialyzed in a dialysis tubing against phosphate buffer or normal saline or glucose solution.2. 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.3. Centrifugation The niosomal suspension is centrifuged and the supernatant is separated. The pellet is washed and then resuspended to obtain a niosomal suspension free
Characterization of NiosomesA. Entrapment Efficiency• Entrapment efficiency = (Amount entrapped total amount) x 100B. Vesicle Morphology• Light Microscopy• Photon Correlation Microscopy• Freeze Fracture Electron Microscopy• Confocal laser scanning Microscopy• SEM• TEMC. In-vitro release
Factors affecting vesicles size, entrapmentefficiency and release characteristicsDrugAmount and type of surfactantCholesterol contentMethods of preparation
Marketed ProductsLancome has come out with a variety of anti-ageing products which are based on niosome formulations. L’Oreal is also conducting research on anti-ageing cosmetic products.
Applications1) Targeting of bioactive agentsa) To reticulo-endothelial systemb) To organs other than RES2) Neoplasia Doxorubicin Niosomal delivery of Doxorubicin to mice bearing S-180 tumor increased their life span and decreased the rate of proliferation of sarcoma3) Leishmaniasis4) Delivery of peptide drugs Oral delivery of 9-desglycinamide, 8-arginine vasopressin entrapped in niosomes increase stability of peptide significantly.
5) Immunological application of niosomes enhance the antibody production in response to bovine serum albumin6) Niosomes as carriers for Hemoglobin7) Transdermal delivery of drugs by niosomes e.g. erythromycin
ConclusionThe concept of incorporating the drug into niosomes for a better targeting of the drug at appropriate tissue destination .They presents a structure similar to liposome and hence they can represent alternative vesicular systems with respect to liposomesNiosomes 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, parentral, etc.
REFERENCESVyas S.P. , Khar R.K. ,Targeted & Controlled Drug Delivery, Novel Carrier Systems, CBS Publication , 2002 ,Page No.249-279Malhotra M. and Jain N.K. Niosomes as Drug Carriers. Indian Drugs 1994, Page No: 81-86.Chandraprakash K.S., Udupa N., Umadevi P. and Pillai G.K. Pharmacokinetic evaluation of surfactant vesicles containing methotrexate in tumor bearing mice. Int. J. Pharma. 1990; R1-R3: 61.www.pharmainfo.netwww.sciencedirect.com