Jonathan Yuxuan Chen
BME PhD Defense Presentation

Date: 2025-10-31
Time: 11 AM
Location / Meeting Link: In-person: IBB 1128 Suddath Room; Zoom: https://gatech.zoom.us/j/99190697471

Committee Members:
Mark Prausnitz (Advisor); Blair Brettmann; Krishnendu Roy; Steven Schwendeman; Johnna Temenoff


Title: DEVELOPMENT AND CLINICAL TRANSLATION OF MICRONEEDLE PATCHES FOR LONG-TERM CONTRACEPTION AND CYSTIC FIBROSIS DIAGNOSIS

Abstract:
Access to quality and timely healthcare remains a bottleneck for improving treatment outcomes in developing regions and rural areas. This accessibility gap largely stems from the need for specialized personnel, equipment, and logistics, leading to poor adherence to long-term health management and delayed diagnosis. For example, 50 million women in Sub-Saharan Africa experience an unmet need for long-acting yet self-applicable contraception. Even in developed countries, the sweat test to diagnose cystic fibrosis (CF), the most common life-limiting genetic disorder in the United States, is only performed at specialized CF centers resulting in delayed diagnosis. Microneedle (MN) patches for sustained drug delivery and point-of-care diagnosis are especially valuable in addressing this accessibility gap. MN patches can be easily applied to penetrate the superficial skin layer for efficient drug delivery into the skin without causing significant discomfort or bleeding. The solid and dry MN formulation that remains in skin after application also removes the need for cold-chain logistics and sharps wastes. In this study, we optimized biodegradable MN patches for the sustained delivery of a contraceptive hormone etonogestrel (ENG) for over one month, and have demonstrated the clinical potential of dissolving MN patches to induce sweating for point-of-care rapid diagnosis of CF via sweat test. For long-acting contraception, in Aim 1, we optimized the solvent-casting formulation and process to fabricate biodegradable MN patches with efficient skin implantation and extended drug-release profile. First, we established two casting formulations with minimal mold interaction, moderate removal rate, and/or borderline polymer solubility to achieve desired material distribution to facilitate MN detachment in skin. Second, we found that centrifuge-based casting and heat annealing procedures generated MNs with lower porosity and improved ENG encapsulation. The optimization efforts not only extended the release duration of ENG to 56 days, but more importantly provided a framework for fabricating biodegradable MN patches with desired properties. For point-of-care diagnosis of CF, in Aim 2, we first conducted a first-in-human clinical study involving 50 healthy adults to demonstrate the tolerability and effectiveness of dissolving MNs to deliver pilocarpine nitrate (PN) into skin for sweat induction. To further enable point-of-care rapid diagnosis of CF without certified professionals and specialized analysis equipment, in Aim 3, we developed a micro-sweat test patch (mSTP) integrating a PN-loaded MN patch with microfluidics and microelectronics. Rational design of the MN patch formulation and geometry facilitated consistent sweat collection and minimal lead time until diagnosis. In a clinical validation study involving 10 healthy adults and 5 CF patients, mSTP generated reliable sweat chloride measurements within 30 min. Altogether, this thesis demonstrated the engineering principles and promising clinical potential of MN patches to improve access to healthcare through sustained drug delivery and point-of-care diagnosis from sweat biomarkers.