Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy

Isabella C Young; Priya Srinivasan; Roopali Shrivastava; Rima Janusziewicz; Allison Thorson; Mackenzie L Cottrell; Rani S Sellers; Craig Sykes; Amanda Schauer; Dawn Little; Kristen Kelley; Angela D M Kashuba; David Katz; Richard B Pyles; J Gerardo García-Lerma; Kathleen L Vincent; James Smith; S Rahima Benhabbour

doi:10.1016/j.biomaterials.2023.122260

Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy

Biomaterials. 2023 Oct:301:122260. doi: 10.1016/j.biomaterials.2023.122260. Epub 2023 Aug 3.

Authors

Isabella C Young¹, Priya Srinivasan², Roopali Shrivastava³, Rima Janusziewicz³, Allison Thorson³, Mackenzie L Cottrell⁴, Rani S Sellers⁵, Craig Sykes⁴, Amanda Schauer⁴, Dawn Little⁶, Kristen Kelley⁷, Angela D M Kashuba⁴, David Katz⁸, Richard B Pyles⁹, J Gerardo García-Lerma², Kathleen L Vincent¹⁰, James Smith², S Rahima Benhabbour¹¹

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
² Laboratory Branch, Division of HIV Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA.
³ Joint Department of Biomedical Engineering, North Carolina State University and the University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁴ Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁵ Pathology Services Core, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
⁶ Katmai Government Services, Anchorage, AK, 99515, USA.
⁷ The DESA Group, Columbia, SC, 29223, USA.
⁸ Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
⁹ Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, 77555, USA.
¹⁰ Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
¹¹ Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Joint Department of Biomedical Engineering, North Carolina State University and the University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address: benhabs@email.unc.edu.

PMID: 37549505
DOI: 10.1016/j.biomaterials.2023.122260

Abstract

Globally, there are 20 million adolescent girls and young women living with HIV who have limited access to long-acting, effective, women-controlled preventative methods. Additionally, although there are many contraceptive methods available, globally, half of all pregnancies remain unintended. Here we report the first 3D-printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for HIV prevention and contraception. We utilized continuous liquid interface production (CLIP™) to fabricate MPT IVRs in a biocompatible silicone-based resin. Etonogestrel (ENG), ethinyl estradiol (EE), and islatravir (ISL) were loaded into the silicone poly(urethane) IVR in a controlled single step drug loading process driven by absorption. ENG/EE/ISL IVR promoted sustained release of drugs for 150 days in vitro and 14 days in sheep. There were no adverse MPT IVR-related findings of cervicovaginal toxicity or changes in vaginal biopsies or microbiome community profiles evaluated in sheep. Furthermore, ISL IVR in macaques promoted sustained release for 28 days with ISL-triphosphate levels above the established pharmacokinetic benchmark of 50-100 fmol/10⁶ PBMCs. The ISL IVR was found to be safe and well tolerated in the macaques with no observed mucosal cytokine changes or alterations in peripheral CD4 T-cell populations. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls.

Keywords: 3D printing; Contraception; Drug delivery; HIV; Intravaginal rings.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Administration, Intravaginal
Animals
Delayed-Action Preparations
Female
HIV Infections* / drug therapy
HIV Infections* / prevention & control
Humans
Macaca
Pregnancy
Pregnancy, Unplanned*
Printing, Three-Dimensional
Sheep

Substances

Delayed-Action Preparations

Abstract

Publication types

MeSH terms

Substances

Grants and funding