NIOSOME A Novel Drug Delivery System

Presented by:

Ankita Rai

M.Pharmacy 2nd

semester

0106PY14MP07

CONTENTS

Introduction

General characteristics

Types

Method of Preparation

Factors affecting the physicochemical properties

Evaluation Parameters

Advantages

Disadvantages

Therapeutic Applications

Marketed Products

References

• Definition: Non-ionic surfactant based vesicle.

Nios = non ionic surfactant

somes = vesicles

• Very small and microscopic in size.

• Vesicles are prepared from self assembly of hydrated non

ionic surfactant molecules.

GENERAL CHARACTERISTICS

Biocompatible

Biodegradable

non-toxic

non immunogenic

non-carcinogenic

High resistance to hydrolytic degradation.

The properties of niosomes depends on both composition

of the bilayer & on method of their production.

STRUCTURE

•Hydrophobic drugs

localized in hydrophobic

lamella

•Hydrophilic drugs

localized in

encapsulated aqueous

region

TYPES

Small

Unilamellar

Vesicle

(SUV)

Large

Unilamellar

Vesicle

(LUV)

Multilamellar

Vesicle

(MLV)

Typical Size Ranges: SLV: 20-50 nm – MLV:100-1000 nm

METHOD OF PREPARATION:

1. Ether Injection method(LUV)

2. Hand shaking method(MLV)

3. Reverse phase evaporation technique(LUV)

4. The “Bubble” method

5. Sonication(SUV)

6. Micro fluidization(SUV)

7. Formation of Niosomes from Proniosomes

8. Multiple membrane extrusion method

9. Trans membrane pH gradient drug uptake

process (remote loading) (MLV)

Common stages of all methods of preparation of

Niosomes

Cholesterol+Non ionic surfactant

Solution in organic solvent

Thin film

Niosome suspension

Dissolve in organic solvent

drying

Dispersion(hydration)

Ether Injection

Surfactant+cholester

ol

Dissolve in Diethyl

ether

Inject into aqueous media(60 ̇C)

14 gauge needle syringe

Niosomes(LUV)

Surfactant+Cholesterol

Dissolve in diethyl ether

Evaporate in rotary evaporator

Hydration(with agitation)

Niosomes(MLV)

Hand shaking Method

Surfactant chloroform+PBS w/o emulsion

Surfactant+Cholesterol aqueous phase in vial

ULV ultrasonic vibration probe sonication

(5min at 60 ̇C)

Reverse phase evaporation technique:

Sonication & evaporation hydration Vesicle

s

Sonication:

ML

V

BUBBLE METHOD:

The bubbling unit consists of round-bottomed flask with three necks positioned in water bath to control the temperature.

Water-cooled reflux and thermometer is positioned in the first and second neck and nitrogen supply through the third neck.

Surfactant+cholesterol Dissolved in buffer at pH 7.4 at 70 0

C

Homogenization for 15 min Bubbled at 70 0 c using N 2

gas

Niosome

s

MULTIPLE MEMBRANE EXTRUSION METHOD

Surfactant, cholesterol, diacetyl

phosphate in chloroform Thin film

evaporatio

n Hydration with

aqueous drug

Suspension extruded through

polycarbonate membranes Upto 8 passages

forms vesicles Niosomes

(of controlled size)

MICROFLUIDIZATION: •1submerged jet principle in which two fluidized streams interact at ultra high velocities,

in precisely defined micro channels within the interaction chamber.

• The impingement of thin liquid sheet along a common front is arranged such that the

energy supplied to the system remains within the area of niosomes formation.

•The result is a greater uniformity, smaller size and better reproducibility of niosomes

formed.

FORMATION OF NIOSOMES FROM PRONIOSOMES

Another method of producing niosomes is to coat a water-soluble carrier such as sorbitol with

surfactant.

The result of the coating process is a dry formulation. In which each water-soluble particle is

covered with a thin film of dry surfactant.

This preparation is termed “Proniosomes”.

The niosomes are recognized by the addition of aqueous phase at T > Tm and brief agitation.

T = Temperature.

Tm = mean phase transition temperature

TRANS MEMBRANE PH GRADIENT DRUG UPTAKE

PROCESS (REMOTE LOADING)

Surfactant+chlolester

ol in chloroform evaporatio

n

Hydration using

citric acid

ML

V

3 freeze thaw cycles sonication

Niosomal

suspension

Aqueous solution of

drug

pH 7.0-7.2 using 1M disodium

phosphate

Heat at 60 ̇C for 10 min

niosome

s

FACTORS AFFECTING THE PHYSICOCHEMICAL

PROPERTIES OF NIOSOMES

NIOSOMES

Hydration temperature

Non-ionic surfactant

nature

Nature of encapsulated

drug

Size reduction technique

Membrane additives

EVALUATION PARAMETERS

1. %Entrapment Efficiency:

%EE= (Amount entrapped/Total amount) * 100

2. Size, shape & morphology:

Transition electron microscopy

Freeze fractured microscopy

Optical microscopy

3. Invitro release

4. Invivo release

5. Stability study

6. Membrane rigidity

7. Number of lamellae:

NMR

Small angle X-ray scattering

8. Vesicular surface charge:

Microelectrophoresis

Dynamic light scattering

ADVANTAGES

• Targeted drug delivery

• Reduction in dose

• Decrease in side effects

• Both hydrophilic and lipophilic drugs can be encapsulated

• Improve therapeutic efficacy

• Osmotically active and stable

• Improve oral bioavailability of poorly soluble drug

• Enhance the skin permeability when applied topically

• Can be use through various routes eg. Oral, parentral, topical, ocular etc.

• The bilayer of niosomes protect the enclosed drug from various factors present both inside and outside the body.

S.No, LIPOSOMES NIOSOMES

1. Vesicles made up of concentric

bilayer of phospholipids

Vesicles made up of surfactants with or

without incorporation of cholesterol

2. Size ranges from 10-3000nm Size ranges from 10-1000nm

3. Comparatively expensive Inexpensive

4. Special storage condition are

required

No such requirement

5. Phospholipids used are unstable Non-ionic surfactants are stable

6 Comparatively more toxic Less toxic

Comparison between liposomes &

niosomes:

DISADVANTAGES

• Physicochemical instability

• Time consuming

• Requires specialized equipment

• Insufficient drug loading

THERAPEUTIC APPLICATIONS

1.Targeting of bioactive agents

a) To reticulo - endothelial system (RES)

b) To organs other than RES

2. Neoplasia

eg.Doxorubicin

3. Leishmaniasis

eg.Sodium stibogluconate

4. Delivery of peptide drugs

5. Immunological applications

6. Carrier for hemoglobin

7. Transdermal delivery of drugs

8. Other applications

a)Sustained release

b)Localized drug action

MARKETED PRODUCTS

• Lancome has come out with a variety of anti-

ageing products which are based on

niosome formulations.

L’Oreal is also conducting anti-ageing

products.

REFERENCES

• Malhotra M, Jain NK, Niosomes as drug carriers. Indian drugs 1994;31:81-6.

• Dr Rakesh P. Patel, Niosomes: A unique drug delivery system, vol5 Issue6, 2007, Pharmainfo.net.

• Uchegbu IF, Vyas SP, Non ionic surfactant based vesicles(niosomes) in drug delivery.lnt J Pharm1998;172:33-70.

• Chouhan S. and Luorence M.J., The preparation of polyoxyethylene containing non ionic surfactant vesicles. J.Pharm.Pharmacol 1989;41:6p.