Jonathan Chen
BME PhD Proposal Presentation

Date:2022-05-18
Time: 2:30PM-4:00PM
Location / Meeting Link: https://bluejeans.com/576928284/9952?src=join_info

Committee Members:
Dr. Mark Prausnitz (Advisor) Dr. Blair Brettmann Dr. Krishnendu Roy Dr. Steven Schwendeman (University of Michigan) Dr. Johnna Temenoff


Title: Formulation and Fabrication Optimizations of Microneedle Patches for the Controlled Release of Contraceptive Hormones

Abstract:
According to the United Nations, 190 million women of reproductive age are experiencing an unmet need in contraception, largely due to lack of access especially in developing regions. To achieve universal access to contraception, there is a need for novel long-acting contraceptive delivery methods that are self-administrable. To address this need, biodegradable microneedles (MNs) have emerged as a promising platform. Each MN patch contains an array of micro-to-milli-meter-scale needle-like structures. When inserted into skin, the MN tips made of a biodegradable polymer encapsulating the drug detach from the patch backing and release the payload continuously as the polymer slowly degrades. Recently published research has demonstrated initial success using a solvent-casting method to fabricate MNs with biodegradable polyester tips to deliver levonorgestrel (LNG) for 1 month and etonogestrel (ENG) for 2 weeks. However, while user-preference research has discovered the preference for multi-month contraceptive MN patches, strategies to extend the release without compromising tip implantation efficiency is yet to be reported. Prior research in other sustained-release systems and observations from preliminary studies have suggested that understanding and controlling the spatial distribution of polymer and drug within MN tips and around the MN funnel regions are essential to achieving tunable release rates and efficient tip implantation. However, previous research generally applied an empirical approach in formulation and processing designs, thus leaving a significant gap in the rational design of sustained release MN cast formulations. This study aims to systemically determine the effects of formulation and processing factors on material distribution within MN tips as a means of maximizing implantation efficiency and achieving optimal release profiles. We will apply the knowledge to fabricate MNs to achieve delivery of contraceptive hormones (ENG, LNG) for 1 or 6 months with efficient MN tip implantation. Aim 1: Formulate and fabricate a microneedle patch for the sustained release of etonogestrel for 1 month. We will first develop MN patches for the sustained delivery of ENG for 1 month, and experimentally screen for release-modifying factors. MN tip implantation efficiency will be evaluated by ex-vivo pig skin and in-vivo rat skin insertions. In-vitro release kinetics will help to identify the most promising candidate for in-vivo pharmacokinetic studies in rats. Aim 2: Determine the effects of organic solvent formulation and fabrication parameters on the distribution and morphology of biodegradable polymer and levonorgestrel in microneedles. Guided by observations in Aim 1, we will further investigate the hypothesis that solvent formulation and processing affect material distribution in MN tips. We will identify solvent removal mechanisms and characterize solvent-mold-polymer interactions of good solvents for biodegradable polyesters. We will then determine key parameters to fabricate solid and film-less MN tips by characterizing MN tip morphology and film formation from patches fabricated with selected solvents and fabrication conditions. The goal is to provide strategies to fabricate sustained release MNs with solid tips, efficient drug encapsulation, and tip implantation. Aim 3: Optimize a core-shell microneedle to achieve consistent tip implantation in skin and desired release rate of levonorgestrel for up to 6 months. With knowledge acquired from the previous studies, we aim to develop a defect-free shell with a thickness that slows release of drug from an inner core for 6 months, minimize drug migration to the surface that could cause an initial burst drug release, and enable efficient MN implantation in skin through cast solvent and processing parameter selections. Material distribution and performance parameters including tip implantation efficiency and release kinetics will be characterized in vitro and in vivo in rats.