Diksha Mhatre*
Dr. Harshal Tare
The oral route of medication administration is the most practical, although some oral medications may have serious disadvantages, such as decreased bioavailability caused by hepatic first-pass metabolism, stomach irritability, and unpleasant taste. A transdermal strategy has been tried as a solution to these problems because it offers advantages such as skipping the hepatic first-pass metabolism. When it comes to medications with a high first-pass metabolism, topical formulations can demonstrate greater bioavailability than oral routes. It has some restrictions, such as the fact that medications with greater molecular weights cannot reach the horny layer. Drugs with greater or lesser distribution coefficients have trouble entering the bloodstream. Drugs are delivered into the skin using liposomes, but their penetration is limited by their propensity to stay in the upper stratum corneum. New lipid vesicles called highly-deformable vesicles have been created to enhance medication delivery. There are many different forms of this type of vesicle, including ethosomes, transferosomes, and transethosomes, that are created for the administration of cosmetics and medications. Transferosomes are flexible vesicular transporters with a lipid dual-layer architecture and an edge stimulator. Edge stimulator is still present in the formulation in spite of the water which has evaporated. This formulation’s principal drawback is that it is challenging to load hydrophobic medicines in this vesicular system with retaining their elastic characteristics. As a result of this, ethosomes are created. Ethosomes are vesicular transporters made of phospholipids that have a high alcohol content and are hydro-alcoholic. The main drawback of ethosomes is that when applied to surface under non-occlusive state, the ethanol in the mixture evaporates, leading to skin dryness. [3,5] Thus, transethosomes, a combination of transferosomes and ethosomes, are created. Transdermal drug delivery systems use the skin as a conduit for pharmaceuticals, allowing them to enter the bloodstream. A few benefits of this approach are that it avoids first-pass metabolism, is less invasive (some treatments are completely non-invasive), is simple to use, doesn't require the help of qualified specialists, and may require fewer dosages. Substances that are both lipophilic and lipophobic have been administered by transdermal devices. Because of these advantages, pharmaceutical researchers design transdermal drug delivery methods, focusing on enhancing drug penetration through the skin by modifying or avoiding the stratum corneum [1]. Transethosomes are modified ethosomes with an edge activator or permeation enhancer. These are employed to provide a variety of medications via transdermal methods. By increasing hydration and vesicular penetration, they can readily penetrate the skin by fluidizing its layers and enlarging its lipid bilayer. Numerous skin diseases, including vitiligo, psoriasis, atopic dermatitis, and skin cancer, are treated with these nanocarriers. [2,4]
Transdermal Pathway.
Skin barrier.
The stratum corneum, an outer layer of keratinocytes structured in a denser manner to prevent endogenous substances from penetrating the skin, is the important barrier that prevents medications from penetrating. It is a barrier of defense that keeps the majority of medications and foreign substances out of the skin and aids in homeostasis. Drugs can enter the skin through the intercellular, transcellular, and appendage channels thanks to the structural properties of the stratum corneum. Figure 1 illustrates these different paths. The intercellular route, which has been suggested to be the most significant drug delivery mechanism, involves the drug molecules moving between the densely packed lipophilic cells of the stratum corneum and negotiating the intricate lipid matrix between keratinocytes [6]. This pathway is usually used to transport medicinal molecules that are tiny and lipophilic (fat-soluble). Drugs travel straight through the stratum corneum's keratinocytes in the transcellular pathway. This path entails passing through both the watery cellular contents and the lipophilic membranes. The cellular components in between make it one of the most difficult medication delivery routes. The appendageal system uses hair follicles and sudoriferous glands to distribute medications. Although they make up a smaller portion of the skin's surface, hair follicles and sudoriferous glands provide an alternate pathway around the stratum corneum barrier. The platform can therefore deliver nanoparticles via this way [7]. Because of its high concentration of collagen (about 70%) and elastin fibers, the dermis layer—which varies in thickness across different body areas—is principally responsible for the skin's strength and elasticity. Its main job is to clear the lymphatic vessels of contaminants. The innermost layer of skin, known as the hypodermis, is made up mostly of fat cells and acts as a barrier between the skin and the body's structures underneath. These cells serve as shock absorbers, heat insulators, and conduction channels for blood vessels and nerves [7,8]. Fig.no.01
10.5281/zenodo.16018169