The Thin Film Polycaprolactone Device: A platform technology for biodegradable and tunable long acting drug delivery implants.

As healthcare costs rise, demand for reduced healthcare visits and improved efficacy, safety, and user acceptability grow. Among solutions, researchers seek to develop and commercialize long-acting controlled release drug delivery systems. The global revenue for these systems was estimated at $181.9 billion in 2013 with projected revenue growth to $212.8 billion by 2018. [1] Demand for such systems is broad and encompasses applications in the delivery of small molecule pharmaceuticals as well as biologics. Advancements in this area rely on the development of reproducible and controllable fabrication technologies and the availability of materials that are suitable for system duration and design. Such drug delivery systems benefit from an understanding of the underlying mechanisms of controlled release and from easily tunable release kinetics to accommodate pre-clinical through clinical development. Here we introduce the Thin-Film Polycaprolactone Device (TFPD), a tunable and biodegradable long-acting implant platform technology. The platform is based on the use of porous and nonporous thin-film (< 50 µm) Polycaprolactone (PCL), a bioresorbable and biocompatible polymer, as a membrane for controlled or sustained release of an API from a reservoir. The platform is highly versatile, allowing for delivery of small and large molecules alike, in sizes relevant to both ocular and subcutaneous implants. A deep understanding of the fundamental mechanisms related to both membrane and device design leads to the use of empirical models to easily design and tune devices for any given API and indication. As this delivery platform is so diverse in its potential applications, tunability and design models are key platform features and the focus of this dissertation. The following sections lay out practical approaches to tuning PCL degradation, the fabrication and characterization of various styles of PCL thin-film membranes, the design and tunability of membranes to control release and of reservoir devices according to target product profiles for specific indications. These concepts are then applied to the early development of three long-acting implant systems: an ocular implant for protein therapeutics, a subcutaneous implant for antiretroviral HIV pre-exposure prophylaxis, and a miniaturized subcutaneous contraceptive implant