Next-generation 3d Printed Multipurpose Prevention Intravaginal Ring For Prevention of HIV, HSV-2, and Unintended Pregnancy.

Details

• Alternative Title:
  Journal of Controlled Release: Official Journal of the Controlled Release Society, 2024, v. 376: Next-generation 3d Printed Multipurpose Prevention Intravaginal Ring For Prevention of HIV, HSV-2, and Unintended Pregnancy.
• Journal Article:
  Journal of Controlled Release: Official Journal of the Controlled Release Society
• Personal Author:
  Dahl, Denali K. ; Srinivasan, Priya ; Janusziewicz, Rima ; King, Jasmine L. ; Shrivastava, Roopali ; Zhang, Jining ; Little, Dawn ; Bachman, Shanon ; Kelley, Kristen ; Cottrell, Mackenzie L. ; Schauer, Amanda P. ; Sykes, Craig ; Kashuba, Angela D.M. ; Smith, James ; Benhabbour, S. Rahima
• Description:
  Globally, nearly half of all pregnancies are unintended, ∼1.3 million new human immunodeficiency virus (HIV) infections are reported every year, and more than 500 million people are estimated to have a genital herpes simplex virus (HSV-2) infection. Here we report the first 3D printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for prevention of HIV, HSV-2, and unintended pregnancy. The IVRs were fabricated using state-of-the-art Continuous Liquid Interface Production (CLIP™) 3D printing technology using a biocompatible silicone-urethane based resin. Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue. All three active pharmaceutical ingredients (APIs) were loaded in the IVR using a single-step drug loading process driven by absorption. DPV, PTV, and LNG elicited zero-order release kinetics in vitro in simulated vaginal fluid (SVF) at pH 4 and pH 8 relevant to human and macaque vaginal pH respectively. CLIP 3D printed MPT IVRs remained stable after 6 months of storage at 4 °C with no change in physical, dimensional, or mechanical properties and no change in drug concentration and absence of drug degradation byproducts. The MPT IVRs elicited sustained release of all three APIs in macaques for 28 days with median plasma concentrations of 138 pg/mL (DPV), 18,700 pg/mL (PTV), and 335 pg/mL (LNG). Safety studies demonstrated that the MPT IVRs were safe and well tolerated in the macaques with no observed change or abnormalities in vaginal pH and no significant changes in any of the 22 mucosal cytokines and chemokines tested including pro-inflammatory (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, IL-17, IL-18) and anti-inflammatory (IL-10, IL-12) cytokines while the MPT IVR was in place or after its removal. Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy and two highly prevalent sexually transmitted infections (STIs).
• Content Notes:
  Author manuscript
• Subjects:
  • Female
  • Animals
  • Printing, Three-Dimensional
  • Pregnancy, Unplanned
  • HIV Infections
  • Herpes Genitalis
  • Contraceptive Devices, Female
  • Pregnancy
  • Levonorgestrel
  • Antiviral Agents
  More +
• Keywords:
  • Multipurpose prevention
  • Intravaginal rings
  • 3D printing
  • HIV
  • HSV-2
  • Contraception
  • macaques
• Source:
  Journal of Controlled Release: Official Journal of the Controlled Release Society, 2024, v. 376
• DOI:
  https://doi.org/10.1016/j.jconrel.2024.10.059
• ISSN:
  0168-3659 ; 1873-4995
• Pubmed ID:
  39500407
• Pubmed Central ID:
  PMC11866343
• Document Type:
  Text
• Funding:
  R01 AI162246/AI/NIAID NIH HHSUnited States/ ; CC999999/ImCDC/Intramural CDC HHSUnited States/ ; P30 AI050410/AI/NIAID NIH HHSUnited States/ ; R01 AI150358/AI/NIAID NIH HHSUnited States/ ; R61 AI136002/AI/NIAID NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  1209-1224 (36 pdf pages)
• Volume:
  376
• Download URL:
  https://stacks.cdc.gov/view/cdc/261939/cdc_261939_DS1.pdf
• File Type:
  [PDF - 2.41 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:a754a18db516bc64672ecfdf502f851aaec825f3fe8f16f5dc3ea3cd9c1a6e89fe8d4fdb8beef6c536f8ce7aa456635346ed120dd511fee39ba40764fbbda957