Formulation and Enhancement Strategies for Decontamination and Drug Delivery Into Healthy and Diseased Skin

Abstract

Despite the significant benefits of the oral and intravenous route of drug administration, there are many problems, such as first-pass metabolism and invasiveness, ultimately leading to poor patient adherence. In the past few decades, it has been established that transdermal drug delivery provides many advantages compared to other drug administration routes. The transdermal route allows drug substances to reach the systemic circulation directly across the skin barrier, thereby increasing bioavailability and patient compliance. Developing transdermal delivery systems that fit into the routine and lifestyle of end-users is critical to the success of a biomedical intervention. Topical and transdermal drug delivery has been studied extensively, mainly on intact/healthy skin. But it is equally relevant to evaluate the enhancement or retardation of these molecules into and across damaged skin. In vitro investigation of healthy and diseased human skin would provide a better understanding of the effect of diseases on drug permeation or retention. Hence, our research focused on studying the extent of absorption and retention of methotrexate into and across healthy as well as diseased human skin. We also screened physical enhancement techniques such as microneedle and iontophoresis to enhance methotrexate delivery into and across the skin. Other aims of our research focused on screening chemical enhancement techniques to evaluate the enhancement in the delivery of olanzapine and raloxifene across the skin. We used chemical enhancers such as oleic acid, oleyl alcohol, and isopropyl myristate that can disrupt the lipid packing of skin and increase the drug partitioning into and delivery across the skin. Based on these findings, we formulated different transdermal delivery systems for the sustained delivery of olanzapine and raloxifene according to their different physicochemical properties, dosage regimen, and as feasible for their indications. Our last aim focused on chemical warfare agents that are toxic blister-causing agents developed a century ago that continues to be a potential threat to public health. Our strategy was to develop a foam-based formulation loaded with antidotes that can rapidly and effectively decontaminate the chemical warfare agent from skin. This can be a promising strategy to attenuate cutaneous damage and thereby treat lewisite toxicity.