• Facilitated Topical and Transdermal Delivery of Small Molecules

      Yeh, Jihee; College of Pharmacy
      The skin is the largest organ of the body that is easily accessible and can be utilized as a route of administration to deliver drugs locally and systemically to achieve targeted therapeutic effects. It provides several advantages over conventional routes of administration (e.g. oral and parenteral) such as bypassing first-pass metabolism, reduction of adverse effects and enhanced patient compliance. However, drug delivery through skin can be challenging due to protective barrier of the skin, especially stratum corneum. Stratum corneum serves as a rate-limiting layer and only allows the permeation of drug molecules with certain physicochemical properties. Chemical enhancers can be used to reversibly alter the structure of stratum corneum to be more permeable without causing long-term compromise of the skin. Also, physical enhancement technique such as iontophoresis utilize an additional energy as a driving force to actively disrupt the barrier nature of stratum corneum to enhance the drug delivery.In the present study, different enhancement strategies such as addition of permeation enhancers to the drug formulation and/or electrically assisted technique such as anodal and cathodal iontophoresis were investigated to enhance the delivery of therapeutic (N-acetylcysteine and minoxidil) and dermatological (adapalene) drugs into and across the skin. Also, iontophoresis was explored for enhancement of topical and transfollicular drug delivery. In summary, chemical enhancers and physical enhancement technique were shown to significantly enhance the skin permeation of different drugs into and across the skin, as compared to their respective passive permeation controls. Furthermore, studies of iontophoresis with different durations of current application revealed that lower duration was adequate to achieve significant amount of minoxidil in hair follicles with reduced amount of drug penetration across the skin, thereby potentially minimizing systemic exposure.