Next Generation 3D-Printed Intravaginal Ring for Prevention of HIV and Unintended Pregnancy

Details

• Alternative Title:
  Biomaterials
• Personal Author:
  Young, Isabella C. ; Srinivasan, Priya ; Shrivastava, Roopali ; Janusziewicz, Rima ; Thorson, Allison ; Cottrell, Mackenzie L. ; Sellers, Rani S. ; Sykes, Craig ; Schauer, Amanda ; Little, Dawn ; Kelley, Kristen ; Kashuba, Angela D. M. ; Katz, David ; Pyles, Richard B. ; García-Lerma, J. Gerardo ; Vincent, Kathleen L. ; Smith, James ; Benhabbour, S. Rahima
• Description:
  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/10| 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.
• Subjects:
  • Pregnancy
  • Humans
  • Female
  • Animals
  • Sheep
  • Pregnancy, Unplanned
  • Delayed-Action Preparations
  • Administration, Intravaginal
  • HIV Infections
  • Macaca
  More +
• Keywords:
  • contraception
  • drug delivery
  • HIV
  • intravaginal rings
  • 3D printing
• Source:
  Biomaterials. 301:122260
• Pubmed ID:
  37549505
• Pubmed Central ID:
  PMC11537264
• Document Type:
  Journal Article
• Funding:
  R01 AI150358/AI/NIAID NIH HHSUnited States/ ; CC999999/ImCDC/Intramural CDC HHSUnited States/ ; R01 AI162246/AI/NIAID NIH HHSUnited States/ ; R01 AI176949/AI/NIAID NIH HHSUnited States/ ; R61 AI136002/AI/NIAID NIH HHSUnited States/
• Volume:
  301
• Download URL:
  https://stacks.cdc.gov/view/cdc/168907/cdc_168907_DS1.pdf
• File Type:
  [PDF - 3.05 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:a8b9e0f158dcd95600a13a97a71bb737580fd1917807e9076bdca70fb9e0da86b0f071ea65d5ab85bef817046047dcfd78e7319cdac19f663ead32160e2f4ccd