Browsing Research, Student by Author "Kale, Madhura"
Enhancement Technologies for Delivery of Small Molecules Into and Across SkinKale, Madhura; College of PharmacyTransdermal drug delivery is a non-invasive route of drug administration through the skin. It offers several benefits, such as bypassing the first-pass metabolism, avoiding fluctuations in plasma concentrations, and easy termination of therapy. Furthermore, local and systemic delivery via this non-invasive route makes it patient-friendly, and this route avoids compliance issues, especially for pediatric and geriatric populations. However, although unionized drugs, having molecular weight <500 Da and moderate lipophilicity (log P 1-3) can passively permeate through the skin, larger molecules and hydrophilic drugs cannot pass through the stratum corneum, the tightly packed lipophilic layer which acts as a barrier to drug delivery. Thus, to overcome this barrier, physical enhancement techniques are applied to achieve permeation into and across the skin. Physical enhancement techniques like iontophoresis, skin microporation using microneedles or an ablative laser, and microdermabrasion have been explored for their drug delivery potential. In this study, we evaluated the topical delivery of nordihydroguaretic acid (NDGA), a compound having the potential to attenuate arsenic toxicity. Studies showed that this compound has the potential to get retained in the skin, which is the target site of delivery. Also, skin exposed to UV radiation too showed similar delivery with that of normal skin. Thus, topical delivery of NDGA is feasible for reducing arsenic toxicity. We also evaluated the topical delivery of kinetin, an antiaging phytohormone that inhibits senescence in plants and helps increase catalase activity. We enhanced the topical delivery using two approaches: increasing the drug loading in the formulation and using microdermabrasion. Our studies showed that increasing the drug loading as well as abrading the skin led to enhancement in the topical delivery of kinetin. We also evaluated the transdermal delivery of donepezil, a cholinesterase inhibitor that is used for managing Alzheimer’s. Physical enhancement were used alone and in combination to control the delivery of donepezil. We observed that the flux profiles could be tailored successfully using a combination of skin microporation and iontophoresis, and therapeutic levels of donepezil can be delivered. In this project, we also developed an iontophoretic patch for the transdermal delivery of zanamivir. A conducting crosslinked chitosan membrane was formulated that, upon hydration, can conduct current. Prophylactic levels of zanamivir were delivered transdermally with this iontophoretic patch. Thus, we successfully delivered pharmaceutical actives across the skin using passive and physical enhancement techniques that have the potential to manage diseases and help patients lead better lives.