NI S MESA Presentation by

P. RAJESHWARRAODepartment 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 L’Oreal.

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 C12–C18 (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

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

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.

Factors influencing Methods of Niosome Preparation

Nature of the encapsulated drug

Surfactant and lipid levels

Temperature of hydration

The hydrating temperatures used to make Niosomesshould 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 100–140 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 (µL/µmol surfactant)

Encapsulation Efficiency

Encapsulated drug to surfactant (µmol/µmol 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 - DSC, ESR, NMR

Surface Chemical Analysis - 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