ABSTRACT
INTRODUCTION Skin is the largest organ in the human body and functions as a protective barrier. The large surface area (1.8 m2) and easy accessibility of skin make it one of the attractive routes for drug delivery. However, the unique bioarchitecture of skin limits the transport of molecules through it (1). The skin is primarily divided into epidermis, dermis, and subcutaneous tissue. Epidermis is again subdivided into stratum corneum (SC), stratum lucidum, stratum granulosum, stratum germinativum, and stratum basale [Fig. 1(A)]. Stratum basale is the germinal layer which continuously divides to produce new keratinocytes that move to outer layers finally to form a horny layer of dead cells in the SC. It takes 2 to 3 weeks for the migration of keratinocytes from the basal layer to finally shed off from the SC. The skin also has appendages such as hair follicles and sweat pores, which constitute 0.1% of the total skin surface area. The hair follicles originate from the dermis and terminate at the surface of the skin. Although the SC is only 10 to 20 m thick, it forms a formidable barrier for the exchange of solutes and moisture. It is made up of stacks of keratin-filled corneocytes interdispersed by tightly arranged lipid bilayers (2). The intercellular lipids mainly consist of free fatty acids, ceramides, and cholesterol (2). Molecules can penetrate the skin by three main routes: (i) intracellular (across the corneocytes), (ii) intercellular lipids, and (iii) appendageal [Fig. 1(B)]. The intercellular lipids are the major transport pathways for most drugs, in which the molecule has to pass through successive hydrophilic and hydrophobic domains in the lipid bilayers. On the other hand, the skin appendages serve as a shunt pathway for drug molecules. Since the appendages occupy only a fraction of the skin surface, they contribute very little to the drug transport. However, the appendages constitute a significant pathway for the iontophoretic transport of charged molecules and the penetration of particulate systems (3,4). Once the molecule crosses the SC and subsequently the viable epidermis, it is absorbed through the blood vessels in the dermis [Fig. 1(A)].
