(M-487) Fuse-based Pulsatile Drug Delivery Device for In Vitro Fertilization

Infertility is an increasingly common problem with 1 in 6 people worldwide being affected according to the World Health Organization's 2023 data. In-Vitro fertilization is the primary treatment utilized by couples struggling to conceive. However, this treatment has low efficacy in part due to the stringently timed self-dosing regimen. Herein we demonstrate an implantable device pre-programmed to release medication at the proper times, avoiding both the discomfort of self-injection and the potential for error in the time of administration. 

The body of the device is made out of polycaprolactone (PCL) which is stamped into the desired device shape using 3D printed molds. For release studies, the reservoirs were manually loaded with Fluorescein isothiocyanate (FITC). Then, the devices were covered with a surface-degrading polymer fuse made of Cellulose Acetate Phthalate and Pluronic (CAPP) via spin coating. Lastly, the devices were encapsulated in PCL, and trimmed to allow one edge of the fuse to be exposed. To quantify release, the devices were isolated in 40% Fetal Bovine Serum (FBS) at body temperature and humidity. Every 8 hours, the fluorescence of the solution was recorded, and the solution replaced. FITC fluorescence was plotted against time to visualize release. 

We created a three-reservoir prototype of the device to determine if precise intervals of drug release could be reliably achieved from the implant. FITC was loaded into the reservoirs, which were designed to release every 3 days. The degradation of the fuse was tracked both visually and through FITC release via a microplate reader. We observed linear degradation of the fuse over time, which affirms the goal of a reliable, timed, sequenced release as the degradation uncovers each reservoir. The FITC release data (Fig. 1) affirms the same goals. All three reservoirs released in sequence, with each pulse evenly spaced three days apart as designed, and rapidly released. The first dose is likely higher in magnitude due to FITC contamination from manual packing and will be mitigated using our newly acquired BioDot 1520 BioJet EliteTM dispenser. This general strategy will be used in future studies to produce devices of varying release schedules and quantities as the fabrication process is optimized. 

This research is supported by the Ole Miss Nanoengineering Summer REU (NSF ENG/EEC 2148764). Additional thanks to the rest of the students in the iNBS Lab.

Human Reproduction Open, Volume 2023, Issue 2, 2023. Purity Njag, Wim Groot, Jelena Arsenijevic, Silke Dyer, Gitau Mburu,  James Kiarie.