Niosome - A Versatile Tool in Transdermal Drug Delivery

 

Shashikant Chandrakar and Swarnalata Saraf*

Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010 India.

 

 

ABSTRACT

The stratum corneum plays a crucial role in barrier function for transdermal drug delivery. Despite major research and development efforts in transdermal systems and the advantages of these routes, low stratum corneum permeability limits the usefulness of topical drug delivery. To overcome this, methods have been assessed to increase permeation. One controversial method is the use of vesicular system, such as niosomes, whose effectiveness depends on their physicochemical properties. This review focuses on effect of niosomes on enhancing drug penetration, and defines the effect of composition, size and type of the vesicular system on transdermal delivery.

 

INTRODUCTION

The skin covers the total surface of the body and function as a barrier between the human body and its external environment. Transdermal drug delivery uses the skin as an alternative route for the systemically acting drug. This drug delivery route can have several advantages compare with oral drug administration1,2. First of all  it circumvents the variable that could influence gastro intestinal absorption such as pH, food intake and gastrointestinal motility. Secondly it circumvents the hepatic metabolism and is therefore suitable for drugs with a low bioavailability. Thirdly transdermal drug delivery system can give a constant control drug input, decreasing the variations in drug plasma levels, thus reducing the side effects particularly of drugs with narrow therapeutics window3-5.

 

Despite many advantage of the skin very less drugs are available for transdermal delivery. The reason behind that is low permeability of stratum corneum present on skin. It has been accepted that the highly organized crystalline lipid lamellae play an essential role in the barrier properties of the stratum corneum. Many technique have been aimed to disrupt and weaken the highly organized intercellular lipids in an attempt to to enhance drug transport across the intact skin, one of them is the vesicle formulation as skin delivery system6- 9.  

 

NIOSOME AS DRUG CARRIER:

1.    Vesicle act as a local depot for the sustain release of dermally active compounds Including antibiotic, contraceptive, non steroidal anti inflammatory drug anticancer drug.

2.    The penetration of individual vesicles into the lipid layer of the stratum corneum act as penetration enhancer and facilitate the dermal delivery leading to higher localized drug concentration.

3.    The vesicle may serve as rate limiting membrane barrier for the modulation of systemic absorption of the drug6,11,16.

 

AdvaNtage of Niosome:

1.      Noisome loaded with drugs for dermal application are aimed to preferentially show interaction with the inflamed tissue without exerting an immediate action. Adsorption and fusion of noisome on the surface of


skin leading to high thermodynamic activity gradient     of drug at the interface which is the driving force for permeation of lipophilic drug2,10,11.

2.      Noisome have distinct advantages over conventional dosage forms because the particle can act as drug containing reservoirs12,13.

3.      Modification of particle composition or surface can adjust the affinity for the target    site and the slowing drug release rate may reduce the toxicity of drug, therefore this carrier play an increasing important role in the transdermal drug delivery6,14,15.

                          

Figure.1 [1]

 

MECHANISM OF ACTION: 

In the literature several mechanisms have been described for transdermal delivery of the drug when the noisome act as penetration enhancer. The main mode of action is a penetration of the lipid organization in the stratum corneum, thereby increase the transport rate of solute across the skin. It has been suggested that that vesicle skin interaction can occur  at the skin surface as in the deeper layer of stratum corneum. Hafland et al and Abraham et al have demonstrated adsorption and fusion of vesicles on to the skin surface, resulting in formation of lamellae and rough structure on top of the outer most corneocytes. Changes in deeper layer of the stratum corneum were observed after treatment of the skin with nonionic surfactant vesicles16,17,18,41.

 

CHARCTERISTIC OF VESICLE FOR TRANSDERMAL DELIVERY:

Size:

Uchegbu et al reported that submicron size of noisome is optimum for transdermal delivery of drug. Brian et al also demonstrated that vesicle more than 10micrometer remains on skin surface and the vesicle of 3-10micrometer concentrate in follicle and less than 3micrometer penetrate the stratum corneum2,11.

 

Shape and morphology:

Vesicle with hexagonal shape gives lower penetration value than spherical shaped16,22. Fang et all also reported in his studty that the nano size range of niosome formulation give better permeation of enoxacin as compare  to the micron size of the niosome26.

 

Surface charge:

The outer layer of the skin is negatively charged therefore positively charge particle absorbed easily by the skin and with the same negatively charged noisome is not suitable for transdermal delivery of the drug. Fang et al reported that the lower permeation enoxacin across the skin,   negatively charged niosome could be attributed to a repulsion within the skin surface in physiological condition26. Haung et al also reported that the better permeation and adsorption of the cationic noisome as a gene carrier in his study28.

 

NIOSOME IN CANCER THERAPY:

Uchegbu et al. (1995) in his study demonstrate that the cholesterol containing Doxorubicin nonionic surfactant vesicle produced relatively protracted blood level probably as a consequence of slow release of entrapped drug. Cholesterol free noisome were generally found to be more effective than other carrier system,  as the reduced cardiac level was noted following its administration. The doxorubicin levels determined in lungs were noticeably higher after nonionic vesicle administration as compared to free drug. It was conceivably assumed those non-ionic surfactant vesicles are not completely sieved out by alveolar capillaries thus retention of substantial number of non ionic surfactant vesicles could be accounted for higher drug tissue levels. The increase in drug level may also be attributed to rapidly proliferating alveolar phagocytic cells within the basement epithelium which could effectively intercept the particular carriers from the circulation18, 31,40. 

 

Therapeutic advantage:

·        They prolong drug effect due to longer circulation time than with non-encapsulated drug.

·        They are sequestered as particle to the target tumors location.

·        Toxicity is reduced.

·        Drugs are protected from metabolism and immune attack until they reach their targets.

·        They are confined to a chosen anatomical compartment.

·        They are directed to target cell by attachment of ligand.

·        Selective local release from carrier is a function of physical factor such as the local temperature or pH. Permeability barrier are circumvented by endocytosis or fusion of carrier with cells(5,18,20,31,42).

 

NIOSOME AS A PENETRATION ENHANCER:

Abraham et al demonstrate that the enhanced delivery through the stratum corneum of noisome encapsulated drug in his studty29. The higher flexibility of this vesicle is responsible for the improved trasdermal penetration .The main route of vesicle penetrartion is, through the intracellular route across the skin(30,44). Vesicle penetrate irregularities between the intracellular lipid lamellae .The different molecular shape of the amphipiles  molecule , render the membrane more flexible. Because of the flexibility the membrane the vesilce changes its shape easily due the stress , therefore  such vesicle require significant less energy  to pass through the small pores , and penetrate into the deeper layer33,34,41,43 .

 

NIOSOME AND SUSTAIN DRUG DELIVERY:

Ibrahim et al reveals the sustained release of ketorolac from hydrated niosome of span 60 in his study. The release of the ketorolac from niosomal gel was retarted    as compare to polymeric gel. Cholesterol content affect the release of the drug from the gel formulation of the niosomal system27.  How et al. also demonstrate the prolong release of the colchicine from the niosomal

 

 

Table .1 Niosome and therapeutic application in dermal drug delivery(21-28)

S no.

system

Drug/ API

Category

Reference

1

2

3

4

5

6

7

8

Niosome

Niosome

Niosome

Niosome

Niosome

Niosome

Niosome

Niosome

Flurbiprofen

Levonorgestrel

Nimesulide

Dithranol

Ketoconazole

Enoxacin

Ketorolac

D.N.A. Loaded non-ionic surfactant vesicles

NSAIDS

Contraceptive

NSAIDS

Antipsoriatic

NSAIDS

Antibacterial

NSAIDS

Antigen carrier

Reddy Narsimha et al.  (1993).

Jia- You Fang, et al. (2001).

Shahiwala  et al.   (2002).

Agrawal R. et al.  (2001).

Satturwar et al. (2002).

Zia You et al.  (2001).

Ibrahim et al.  (2004).

Huang et al.  (2005).

 

 

 

preparation.  The retardate o release of the drug is due to the presence of the cholesterol which is known to abolish the gel to lipid phase transition of niosome   whatever could be able to effectively prevent leakage of drug from niosome31.

 

Safety profile of niosome:

The HLB no. of the surfactant has no influences on  the toxicity of compound, the more hydrophilic compounds were obviously less toxic. The incorporation of solulan C24 more than 10 mol% are toxic in C16G2 niosome. The length of polyoxyethylene chain or the alkyl chain had not influences on the skin toxicity of alkyl polyoxyethlene noisome as assessed by the cell proliferation of human keratinocytes in vitro. The latter is considered to be a measure of the irritability. However the nature of the linkage (ether or ester) was a determining factor and the more labile ester bond was found to be more toxic than the ether bond32,33,34,45.

 

Comparison with other drug delivery system:

In liposome the phospholipid used are prone to oxidative degradation and hence they must be handled and stored in nitrogen atmosphere. The phospolipid used will interact with the serum component, the high density lipoprotein particularly15,30. High density lipoprotein remove phospolipid molecules from lipid bilayer structure, an event which allegedly leads to their destruction resulting in leakage of entrapped drugs35,36,37.  As compared to liposome, about 50% of phospolipid can be replaced with non-ionic surfactant in niosome preparation, the vesicle stability may be slightly improved. Due to presence of nonionic suefactant in noisome, there may be improvement in the permeation and release of the drugs entrapped through various barrier of body and organs which may improve the targeting efficiency of the drug(38,39).

 

CONCLUSION:

Niosome is a versatile candidate for the transdermal delivery of the drug because of its better penetration through the skin. The presence of cholesterol also retared the release of the  solute and s releases in the sustained manner.Its better  stability than liposome because absence of the phospholipid as structural component making it potential drug delivery system. . The nontoxic nature because the presence of non-ionic surfactant and   handling and storage of niosome require no special condition thus niosome may be better alternative carrier for various drug compared to microsphere, liposome, nanoparticles with improved efficacy.

 

AKNOLEDGEMENT:

Authors are thankful to Chhattisgarh Council of Science and Technology (CG-COST), Chhattisgarh and All India Council of Technical Education (AICTE), New Delhi for financial support under Research Promotional Scheme (RPS).

 

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Received on 20.10.2008

Accepted on 12.04.2009     

© A&V Publication all right reserved

Research Journal . of Pharmaceutical Dosage Forms  and Technology. 1(1): July.-Aug. 2009, 01-04