NIOSOMESMohammed Faizan

M.Pharm II – sem

B. B. A. U.

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CONTENTS

Introduction

Advantages & Disadvantages of Niosomes

Types of Niosomes

Formulation: Components and their effect

Methods of Preparation

Separation of unentrapped drug

Characterization of niosomes

Routes of Administration

Application of Niosomes

Marketed products

Conclusion

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INTRODUCTION

Niosomes are a novel drug delivery system in which the drug is

encapsulated in vesicles composed mainly of hydrated non-ionic

surfactants with or without cholesterol.

Niosomes are capable of encapsulating both lipophilic and hydrophilic

substances.

This can be achieved by entrapping hydrophilic in vesicular aqueous core

or adsorbed on the bilayer surfaces while the lipophilic substances are

encapsulated by the lipophilic domain of bilayers.

The size of a niosome ranges from some 10 nm up to several micrometers.

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STRUCTURE OF NIOSOMES

Hydrophilic

drugs

located in

aqueous

regions

encapsulate

d

Polar heads

facing

hydrophilic

region

Hydrophobic

drugs

localized in

the

hydrophobic

lamellae

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ADVANTAGES OF NIOSOMES

Niosomes are osmotically active, stable, and have long storage time.

Surface modification is very easy because of functional groups on their

hydrophilic heads.

Highly compatible with biological systems and low toxicity because of their

non-ionic nature.

Bio-degradable and non-immunogenic.

Improving therapeutic performance by protecting the drug from biological

environment, and hence better bio-availability.

High patient compliance because of water-based suspension of niosomes.

They can entrap both lipophilic as well as hydrophilic drugs.

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CONTD..

Unlike phospholipids, handling of surfactants requires no special

precautions and conditions.

They enhance the permeation of drugs through skin.

Increases the oral bio-availability.

Access to raw materials is convenient.

Targeted drug delivery.

Niosomes enhances the absorption of some drugs across cell membranes

to localize in targeted tissues and elude the reticulo-endothelial system.

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DISADVANTAGES OF NIOSOMES

During dispersion, both niosomes and liposomes are at risk of :-

Aggregation

Fusion

Drug leakage

Hydrolysis of encapsulated drug.

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TYPES OF NIOSOMES

In addition to categorization based on

size, many other types mentioned are:

Proniosomes

Surfactant ethosomes

Elastic niosomes

Polyhedral niosomes

Discomes (disk-shaped vesicle)

Aspasome (ascorbyl palmitate vesicle)

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FORMULATION:

Components and their effects

NON-IONIC SURFACTANT:

These are the basic components of niosomes which upon hydration form

lamellar microscopic and nanoscopic vesicles.

They are stable, compatible and non-toxic.

Ability to maintain pH upto physiological pH.

Functions such as solubilizers, wetting agents, and permeability enhancers.

They are inhibitors of p-glycoprotein, hence increasing bio-availability of

some anti-cancer drugs and HIV-drugs.

Examples: Brij 30, Brij 58, Sorbitan fatty acid esters, Gemini surfactants(two

hydrophobic chains and two hydrophilic head groups), and Bola-

amphiphiles(two polar heads connected by long hydrophobic spacers).

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HLB Value Impact on Formulation

14 – 16 Does not produce niosomes

8.6 Increase entrapment efficiency of niosomes

1.7 – 8.6 Decreases entrapment efficiency

>6 Needs to add cholesterol in formation of

bilayer vesicle

Lower value Needs to add cholesterol to increase stability

CONTD..

PROPERTIES OF NON-IONIC SURFACTANTS:

HLB(Hydrophilic-lipophilic balance) :

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CONTD..

Impact of chain length and hydrophilic head group:

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CONTD..

EFFECT OF TEMPERATURE:

Temperature of the hydration medium plays a major role in the formation of vesicles and affects their shape and size.

The temperature should always be above the gel to liquid phase transition temperature of the system.

CRITICAL PACKING PARAMETER(CPP):

The type of vesicle formed can be

predicted. It indicates the surfactants

ability to form spherical micelle.

CPP<0.5 - form micelles

CPP=0.5-1 - forms spherical vesicles

CPP>1.0 – forms inverted micelles

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CONTD..

HYDRATION MEDIUM:

Phosphate buffer of various pH is used as hydration medium in formulation

of niosomes.

The actual pH of the hydration medium depends on the solubility of drug

being encapsulated.

CHOLESTEROL:

It imparts rigidity to vesicles.

It influences membrane properties such as aggregation, ion permeability,

elasticity, enzyme activity and size and shape.

Amount of cholesterol added depends on the HLB value of the surfactant.

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CONTD..

AMOUNT OF SURFACTANT/LIPID:

The maximum amount of Surfactant / Lipid used to prepare niosomes is

generally 10 – 30 mmol/L (1 – 2.5% w/w).

EFFECT OF ENCAPSULATED DRUG:

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METHODS OF PREPARATION15

THIN FILM HYDRATION METHOD(TFH)

Surfactant +cholesterol dissolved in organic solvent in round bottom flask

Rotary Vacuum Evaporator

Thin film is formed on flask by removal of organic solvent

Water/PBS

Dry film is hydrated above the transition temperature of the surfactant

MLVs were formed

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HAND SHAKING METHOD

Surfactant +cholesterol dissolved in organic solvent in round bottom flask

Rotary evaporator

Thin film is formed on flask by removal of organic solvent

Completely dried film was directly hydrated with aq. Sol.

One hour mechanical shaking

milky appearance

MLVs are formed

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THE “BUBBLE” METHOD

Novel technique of niosome preparation without the use of organic solvent

(Green Method).

In this technique, surfactant, additives, and PBS (pH 7.4) were transferred

into a glass reactor with three necks.

The reactor is positioned in a water bath to control the temperature.

The thermometer is positioned in the first neck, nitrogen supplied through

second neck, and water cooled reflux in the third neck.

Niosome components are dispersed at 70 °C and is mixed for 15 sec with

high shear homogenizer and immediately followed by the bubbling of

nitrogen gas at 70 °C .

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ETHER INJECTION METHOD (EIM)

Surfactant + Cholesterol dissolved

in diethyl ether and injected

slowly through a needle in an aq.

Sol. containing drug at constant

temperature of 60°C

Organic solvent was evaporated

using a rotary evaporator

SUVs and LUVs are formed by this

technique.

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REVERSE PHASE EVAPORATION

METHOD(REV)

Surfactant + Cholesterol dissolved inchloroform and PBS, and emulsified toget a W/O emulsion

Sonication

Chloroform is evaporated using rotaryvacuum evaporator at 40 - 60°C

The surfactant/lipid first forms a gel andwas hydrated to form vesicles

LUVs are formed

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SONICATION METHOD

Surfactant + cholesterol mixture is dispersed in 2 mL aqueous phase in vial

Mixture is sonicated for 3 min at 60°C using Titanium probe sonicator

ULVs are formed

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HEATING METHOD

Surfactant + cholesterol separatelyhydrated in PBS for 1 hour under Nitrogenatmosphere at room temperature

15 – 20 min

The solution is heated at 120°C to dissolvecholesterol

60°C

Surfactant is added to buffer in whichcholesterol is dissolved

stirring for 15 min

Niosomes obtained are left at roomtemperature for 30 min & then kept at 4-5°C under nitrogen atmosphere

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MICRO FLUIDISATION TECHNIQUE

It is a process where a solution of surfactant and drug is pumped under

pressure from a reservoir through an interaction chamber packed in ice at

a rate of 100 mL/min.

From the interaction chamber, the solution is passed through a cooling loop

to remove heat produced during micro fluidization.

And returned to the reservoir for recirculation or allowed to exit the system.

The process is repeated until a vesicle of desired size is produced.

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FREEZE AND THAW METHOD

Niosomal suspension, prepared using Thin Film Hydration (TFH) method were

frozen in liquid nitrogen for 1 minute.

Thawed in a water bath at 60°C for another 1 minute.

This method generates frozen and thawed MLVs.

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DEHYDRATION REHYDRATION METHOD

Niosomal suspension prepared by TFH, are frozen in liquid nitrogen.

Then, freeze dried over-night.

Niosome powder obtained is hydrated with PBS(pH = 7.4) at 60°C.

Niosomes are prepared.

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PRONIOSOMES TECHNIQUE

Proniosomes are a stable precursors for the immediate preparation of

niosomal carrier system.

The method involves the coating of 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 formulation is termed as “proniosomes”.

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SEPARATION OF UNENTRAPPED DRUG

GEL FILTRATION:

The unentrapped drug is removed by gel filtration ofniosomal dispersion through a Sephadex-G-50 columnand elution with phosphate buffered saline.

DIALYSIS:

Dialyzed in a dialysis tubing against phosphate bufferor normal saline

CENTRIFUGATION:

The niosomal suspension is centrifuged and thesupernatant is separated. The pellet is washed andthen resuspended to obtain a niosomal suspensionfree from unentrapped drug.

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CHARACTERIZATION OF NIOSOMES

PHYSICAL CHARACTERIZATION

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CONTD..

CHEMICAL CHARACTERIZATION:

Characterization parameters Analytical method/Instrument

1. lipid concentration Barlett assay, stewart assay,

HPLC

2. Cholesterol concentration Cholesterol oxidase assay and

HPLC

3. Cholesterol auto-oxidation. HPLC and TLC

4. Osmolarity Osmomete

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ROUTES OF ADMINISTRATION30

CONTD..31

CONTD..32

APPLICATION OF NIOSOMES

Gene delivery: Manosroi et. al. investigated niosomes composed of span85 and cholesterol can be used for the topical delivery of pDNA encodinghepatitis B surface antigen(HBs Ag).

Vaccine delivery

Leishmaniasis treatment: Niosomes can be used for targeting of drug in thetreatment of diseases in which the infecting organism resides in the organof reticulo endothelial system.

In leishmaniasis parasite invades cells of liver and spleen.

The commonly prescribed drugs are Antimonials, which are related toarsenic, and at high concentration they damages the heart, liver ,andkidney.

Anti-cancer drug delivery

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CONTD..

Delivery of peptide drugs: like insulin and oligo-nucleotide.

Opthalmic drug delivery: Niosomes contain non-ionic surfactants which arenon-antigenic and non-toxic to the eye.

Showed high retention time and no signs of irritancy.

Chronic obstructive pulmonary disease(COPD) drug delivery: ClaudioTerzano et. al. entrapped beclomethasone in niosomes successfully fornebulized drug delivery system.

Brain targeted drug delivery system: Marco Bragagni et. al. developeddoxorubicin brain targeted niosomal formulation, functionalizing with N-palmitoylglucoseamine.

Brain concentration of 2.9 µg/g was achieved after 60 min, whilecommercial solution remained undetectable.

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MARKETED PRODUCTS

Lancôme has come out with a variety of anti-ageing products which are

based on noisome formulations.

L’Oreal is also conducting research on anti-ageing cosmetic products.

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CONCLUSION

Niosomes provide means of incorporating the drug for a better targetingand at appropriate tissue destination .

Niosomes are thoughts to be better candidates drug delivery as comparedto liposomes due to various factors like cost, stability etc.

Various type of drug deliveries can be possible using niosomes liketargeting, ophthalmic, topical, parenteral etc.

Niosomes present a convenient, prolonged, targeted and effective drugdelivery system.

The potential of niosomes can be enhanced by using novel preparationsand modification methods.

Thus, these areas needs further exploration and research so as to bring outcommercially available niosomal preparations.

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REFERENCES

Saeid Moghassemi, Afra Hadjizadeh ; Nano-niosomes as nanoscale drugdelivery systems: An illustrated review; Journal of controlled release 185 (2014) 22– 36.

Alhat babita, Rukari Tushar; Niosomal drug delivery system – Promising drugcarriers, review article; International Research Journal for Inventions inPharmaceutical Sciences; 05/07/2013

N.B. Mahale , P.D.Thakkar , R.G.Mali , D.R.Walunj , S.R.Chaudhari ; Niosomes:Novel sustained release non-ionic stable vesicular systems – An overview ;Advances in Colloid and Interphase Science 183 – 184 (2012) 46 – 54.

Himanshu Anwekar; Liposome- as drug carriers; International Journal OfPharmacy & Life Sciences; Vol.2, Issue 7: July: 2011, 945-95

Baillie AJ, Florence AT, Hume LR, Rogerson A, and Muirhead GT; The preparationand properties of Niosomes - Non-ionic surfactant vesicles; J. Pharm Pharmacol.37(2012), 1985, 863–868.

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