NI S MES

A Presentation by P. RAJESHWARRAO Department of Pharmaceutics THIRUMALA COLLEGE OF PHARMACY

What are Niosomes?

Niosomes are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids.

Use of Niosomes in cosmetics was first done by LOreal.

Structure of a Niosome

Advantages
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 These can increase the oral bioavailability of drugs These can enhance the skin penetration of drugs They can be used for oral, parenteral as well topical use

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

What does mainly a Niosome contain?

Non-ionic Surfactants Steroids

Charge Inducers

Non-ionic surfactant structure

Hydrophilic head groups found in vesicle forming surfactants

glycerol head groups ethylene oxide head groups crown ether head groups polyhydroxy head groups sugar head groups + amino acids sugar head groups (galactose, mannose, glucose, lactose)
Hydrophobic moiety

One or two alkyl or perfluoroalkyl groups or in certain cases a single

steroidal group. Alkyl group chain length is usually from C12C18 (one, two or three alkyl chains. Perfluoroalkyl surfactants that form vesicles possess chain lengths as short as C10 Additionally crown ether amphiphiles bearing a steroidal C14 alkyl or C16 alkyl hydrophobic unit have been shown to form vesicles.

 Hydrophilic Lipophilic Balance (HLB) is a good indicator of the vesicle forming ability of any surfactant. With the sorbitan monostearate (Span) surfactants, a HLB number of between 4 and 8 was found to be compatible with vesicle formation. The water soluble detergent polysorbate 20 also forms Niosomes in the presence of cholesterol.

STEROIDS Cholesterol, Tocopherol Improves the fluidity of the bilayer. Minimizes leaching out of water soluble drug. Abolish gel to liquid transition of liposomal and Niosome systems resulting in less leaky vesicles.

Improves stability in biological fluids reduce

interaction with plasma proteins

CHARGE INDUCERS Dicetyl Phosphate, Sod. Cholate, Stearylamine

Prevents aggregation
Increases drug loading of water

soluble drugs in MLV

Liposomes vs. Niosomes

liposomes are expensive, their ingredients like phospholipids are chemically unstable because of 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. Niosomes do not have any of these problems. Also since niosomes are made of uncharged single-chain surfactant molecules as compared to the liposomes which are made from neutral or charged double chained phospholipids, the structure of niosomes is different from that of liposomes

Factors influencing Methods of Niosome Preparation

Nature of the encapsulated drug Surfactant and lipid levels Temperature of hydration The hydrating temperatures used to make Niosomes should usually be above the gel to liquid phase transition temperature of the system.

NIOSOME PREPARATION
Ether Injection
Injection of an organic solution of surfactants: lipids in an aqueous solution of the drug to be encapsulated which is heated above the boiling point of the organic solvent.

Reverse Phase Evaporation

The formation of an oil in water (o/w) emulsion from an organic solution of surfactants: lipids and an aqueous solution of the drug. The organic solvent is then evaporated to leave Niosomes dispersed in the aqueous phase. In some cases, a gel results which must be further hydrated to yield Niosomes.

Hand shaking
The formation of a surfactant: lipid film by the evaporation of an organic solution of surfactants: lipids. This film is then hydrated with a solution of the drug (hand shaking). The injection of melted lipids:surfactants into a highly agitated heated aqueous phase in which presumably the drug is dissolved or

the addition of a warmed aqueous phase dissolving the drug to a

mixture of melted lipids and hydrophobic drug.

The addition of the warmed aqueous phase to a mixture of the solid

lipids:surfactants.

pH gradient across internal and external Aq. Phase - Ammonium gradient method for Doxorubicin

REDUCTION OF NIOSOME SIZE

Probe sonication which yields niosomes in the 100140 nm size

range.

Extrusion through 100 nm Nucleopore filters size range. In some instances the combination of sonication and filtration (220 nm Millipore filter) has been used to achieve niosomes in the 200 nm size range The achievement of sub-50 nm sizes is possible by the use of a microfluidizer. High-pressure homogenisation also yields vesicles of below 100 nm in diameter although drug loading is ultimately sacrificed to achieve this small size.

ENCAPSULATION OF DRUGS IN NIOSOMES

Encapsulation volume/Trapped volume Volume of aqueous solution entrapped in Niosomes per mole of surfactant (L/mol surfactant)

Encapsulation Efficiency
Encapsulated drug to surfactant (mol/mol of surfactant)

% Encapsulation
Drug entrapped in Niosomes x 100

Total drug added

REMOVAL OF UNENCAPSULATED DRUG

Centrifree - Suitable dilution is necessary

- Higher concentration of lipid blocks membrane

Adv : Rapid, requires small sample volume Disadv : Expensive, Lipid concentration cannot exceed 5mg/mL Gel Chromtography - Sepharose/Sephadex - Liposomes larger size pass through void volume Adv : Sample recovery Disadv : Slow and tedious, dilution of samples

Dialysis - Controlled and minimized by avoiding large dilution steps - Several steps of small dil. vol (5-10 fold original dispersion)

Adv

: Sample recovery

Disadv : Inaccurate and impossible to determine critical point

Protamine Aggregation
Adv : Economical Disadv : Slow with neutral/positive charged liposomes

Contamination of the sample

Ultracentrifugation

- Subjected to high forces, can modify physically

CHARACTERIZATION OF NIOSOMES

Mean Size & Size distribution

Electron Microscopy Dynamic Light

Scattering (PCS)
Surface Potential & Surface pH Micro electrophoresis

No of lamellae

Small angle X ray Scattering, NMR, Electron microscopy -

Structural & Motional behavior

of lipids
Surface Chemical Analysis

DSC, ESR, NMR

XPS, SIMS, NMR

APPLICATIONS
Cancer Antimicrobial agents Leishmaniasis (Amphotericin B) Gene therapy Immunological Adjuvants Liposome entrapped DNA delivery Transdermal drug delivery

Vaccine adjuvants
Enzyme replacement Cosmetics

Topical applications
Pulmonary delivery Lysosomal storage diseases Ophthalmic delivery of drugs