Cellular Permeation Pathways: Current focus of Permeation Enhancers for Effective Drug Delivery

Certain agents that enhance drug transport through the skin, including surfactants, bile salts, and fatty acids, have been shown to exert a similar effect on the oral mucosa. Oral drug delivery offers an attractive method of needle-free drug administration. Unfortunately, oral delivery is often hampered by the poor permeability of drugs across the intestinal epithelium. Although several single chemical permeation enhancers have been shown to alleviate permeability difficulties, this often occurs at the expense of safety. The stratum corneum, oral mucosa and buccal mucosa pose a formidable challenge to formulators of drug delivery systems. Several approaches have been utilized to facilitate entry of drugs into the lower skin layers or mucosal layers. Traditionally, permeation enhancers are designed to deliver high drug concentrations across the barrier into the systemic circulation. The use of many of these agents results in unpleasant or toxic side effects. However, in recent years there has been a search for compounds that exhibit low toxicity, and maintain their enhancing activity. Research in the area of permeation enhancement or retardation is yielding valuable insights into the structure activity relationships of enhancers as well as retardants. The purpose of this review is to identify the major differences in the structural and chemical nature of the per meability barriers between the oral mucosa and skin, to clarify the mechanisms of action of penetration enhancers, and to identify the limitations of certain models that are used to assess the effect of penetration enhancers.