Co-delivery of an HIV prophylactic and contraceptive using PGSU as a long-acting multipurpose prevention technology.

Abstract

Objectives: Poly(glycerol sebacate) urethane (PGSU) elastomers formulated with 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), levonorgestrel (LNG), or a combination thereof can function as multipurpose prevention technology implants for prophylaxis against HIV and unintended pregnancies. For these public health challenges, long-acting drug delivery technologies may improve patient experience and adherence. Traditional polymers encounter challenges delivering multiple drugs with dissimilar physiochemical properties. PGSU offers an alternative option that successfully delivers hydrophilic EFdA alongside hydrophobic LNG.

Methods: This article presents the formulation, design, and characterization of PGSU implants, highlighting the impact of API loading, dimensions, and individual- versus combination-loading on release rates.

Results: Co-delivery of hydrophilic EFdA alongside hydrophobic LNG acted as a porogen to accelerate LNG release. Increasing the surface area of LNG-only implants increased LNG release. All EFdA-LNG, EFdA-only, and LNG-only formulated implants demonstrated low burst release and linear release kinetics over 245 or 122 days studied to date.

Conclusion: PGSU co-delivers two APIs for HIV prevention and contraception at therapeutically relevant concentrations in vitro from a single bioresorbable, elastomeric implant. A new long-acting polymer technology, PGSU demonstrates linear-release kinetics, dual delivery of APIs with disparate physiochemical properties, and biocompatibility through long-term subcutaneous implantation. PGSU can potentially meet the demands of complex MPT or fixed-dose combination products, where better solutions can serve and empower patients.