Journal Article

Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP)

van der Straten, Ariane, Myers, Daniel, Krovi, Sai Archana, Li, Linying, Girouard, Natalie, Creelman, Ben, Johnson, Leah M., Demkovich, Zach R.

2019

Overview

Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) offers the potential to improve adherence by lowering the burden of daily or on-demand regimens of antiretroviral (ARV) drugs. This paper details the fabrication and in vitro performance of a subcutaneous and trocar-compatible implant for the LA delivery of tenofovir alafenamide (TAF). The reservoir-style implant comprises an extruded tube of a biodegradable polymer, poly(ε-caprolactone) (PCL), filled with a formulation of TAF and castor oil excipient. Parameters that affect the daily release rates of TAF are described, including the surface area of the implant, the thickness of the PCL tube walls (between 45 and 200 µm), and the properties of the PCL (e.g., crystallinity). In vitro studies show a linear relationship between daily release rates and surface area, demonstrating a membrane-controlled release mechanism from extruded PCL tubes. Release rates of TAF from the implant are inversely proportional to the wall thickness, with release rates between approximately 0.91 and 0.15 mg/day for 45 and 200 µm, respectively. The sustained release of TAF at 0.28 ± 0.06 mg/day over the course of 180 days in vitro was achieved. Progress in the development of this implant platform addresses the need for new biomedical approaches to the LA delivery of ARV drugs.

• Publisher: MDPI AG,MDPI
• Subject: Antiretroviral drugs / Biodegradation / Disease prevention / Drug delivery systems / Drug dosages / HIV / Human immunodeficiency virus / implant / long-acting drug delivery systems / poly(ε-caprolactone) (PCL) / Polymers / Polyvinyl alcohol / pre-exposure prophylaxis (PrEP) / Silicones / tenofovir alafenamide (TAF) / Transplants & implants