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.

KEYWORDS:

• long-acting drug delivery
• multipurpose prevention technologies
• HIV
• STIs
• contraceptives
• PGS
• PGSU
• biodegradable implants

Acknowledgments

The authors would like to acknowledge the Bill and Melinda Gates Foundation, Dr Dennis Lee, and Calibr, the drug discovery division of Scripps Research, for graciously providing EFdA to complete these studies.

Declaration of interest

The authors are employed by Secant Group, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

J. Cohen, D. Shull, and S. Reed contributed to the conception and design of formulations. D. Shull fabricated the implant samples. J. Cohen and D. Shull performed characterization and ran analytical instrumentation. J. Cohen and S. Reed analyzed and interpreted the data. J. Cohen, D. Shull, and S. Reed drafted the paper. S. Reed revised the paper critically for intellectual content. S. Reed contributed and approved the final version to be published. All authors agree to be accountable for all aspects of the work.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425247.2023.2168642

Additional information

Funding

This paper was not funded.