Transethosomes: A Breakthrough System for Transdermal and Topical Drug Delivery

The major hindrance in transdermal delivery of drugs is complex barrier of stratum corneum. New generations lipid based nano-system, particularly transethosomes have ability to permeate from rigid network of stratum corneum. They have proved to be a promising tool for the transport of drugs. This article reviews these ethanol-based, elastic, and deformable vesicles. The major components that provide the vesicles their distinct properties are phospholipids, ethanol, edge activator

bene ts, it has some challenges, the most common of which is skin acting as a barrier for drug penetration due to its organized structure [4].The barrier properties of skin are due to the outermost layer of the epidermis called the stratum corneum.The stratum corneum consists of corneocytes, proteins and is enveloped in a lipid bilayer that prevents the absorption of drugs.It allows the entry of molecules having lipid solubility, and lower molecular weight [5].

DRUG DELIVERY PATHWAYS THROUGH SKIN
There are basically three main routes for the drug penetration through the layers of skin, which include transcellular, intercellular, and appendageal routes [6].
The transdermal drug administration through the appendageal route is the least used route due to low diffusion rate and small area for absorption [7].The transcellular routes are the major pathway for polar drugs during the percutaneous absorption of the drug and for hydrophilic compounds [8].TRANSETHOSOMES Transethosomes are lipid-based, elastic, Ultra-Deformable Vesicles (UDV).These are uneven spherical shaped carriers that have the ability to encapsulate low as well as high molecular weight drugs [9].After the discovery of transfersomes and ethosomes, the transethosomal system of drug delivery was rst introduced in 2012 [10].The novel transethosomes contain the major bene ts of ethosomes and transfersomes i.e., vesicle elasticity and skin permeation.The structure of transethosomes mainly consists of phospholipids along with ethanol, edge activator (surfactant), and water.Phospholipids being amphiphilic perform the main role in bilayer formation [9].Edge activators like tween 20, tween 60, tween 80, span 60, span 65, span 80, and sodium cholate or sodium deoxycholat, among others, improves the permeability and the exibility of the vesicle [11,12].However, Ethanol (used in concentration up to 30%) is the penetration enhancer and water is the vesicle forming agent [13].Permeation mechanism of transethosomes through skin barrier; transethosomes assist in the drug delivery by enhancing the permeability of the components of the free drug through the skin with the help of vesicle components.Ethanol is the major constituent responsible for the penetration of transethosomes as edge activators alone are not su cient to penetrate into the lower layers of the skin [14,15].Ethanol present in transethosomes causes disruption of the phospholipids in the stratum corneum causing uidization [16].Increased uidization results in increased intracellular space which in turn increases the penetration.Transethosomes instigate hydration that broadens the pore size.This allows the edge activator to utilize its deforming properties to help squeeze the molecule through the stratum corneum despite the smaller diameter of the pores [17].Subsequent to passing through corneum, it goes through feasible epidermis and arrives at the dermis [18].Transethosomes are easy to manufacture and simple to scale up without contribution of re ned apparatus at both pilot plant and modern level.Various strategies are utilized to accomplish smaller vesicular size and these vesicles are fused into gels or creams to increment skin in ltration.The commonly used methods are; a) Cold method, b) Hot method, and c) Mechanical Dispersion method.Transethosomes have the combined properties of both transferosomes and ethosomes exhibiting properties of both skin permeation and deformability, this help to bypass the presystemic metabolism, transethosomes provide a non-invasive route of administration and in diseases or conditions, where patients cannot take drugs orally transethosomes can be an effective route of delivery.Skin allergies or contact dermatitis can be a possibility, reasonable molecular size of the drug is needed for absorption and incomplete formulation of vesicles can lead to coalescence.

C O N C L U S I O N
Ultra-deformable Vesicles (UDVs) have been developed to improve the transdermal drug delivery by augmenting the penetration of the drug molecules through the stratum corneum.Transethosomes have proved to be more effective drug carrier as they have enhanced permeability properties.Transethosomes have combined the penetration abilities of transfersomes and ethosomes by incorporating the edge activator with the ethanol in the vesicle.More advancement in this area may lead to further innovations creating betterment in the eld of pharmaceutics.

Ali J et al.,
Transethosomes for Transdermal and Topical Drug Delivery

Table 1 :
Summarized list of therapeutic agents delivered through transethosomes.