TY - JOUR
T1 - Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy
AU - Young, Isabella C.
AU - Srinivasan, Priya
AU - Shrivastava, Roopali
AU - Janusziewicz, Rima
AU - Thorson, Allison
AU - Cottrell, Mackenzie L.
AU - Sellers, Rani S.
AU - Sykes, Craig
AU - Schauer, Amanda
AU - Little, Dawn
AU - Kelley, Kristen
AU - Kashuba, Angela D.M.
AU - Katz, David
AU - Pyles, Richard B.
AU - García-Lerma, J. Gerardo
AU - Vincent, Kathleen L.
AU - Smith, James
AU - Benhabbour, S. Rahima
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - 3D printing
KW - Contraception
KW - Drug delivery
KW - HIV
KW - Intravaginal rings
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U2 - 10.1016/j.biomaterials.2023.122260
DO - 10.1016/j.biomaterials.2023.122260
M3 - Article
C2 - 37549505
AN - SCOPUS:85166738767
SN - 0142-9612
VL - 301
JO - Biomaterials
JF - Biomaterials
M1 - 122260
ER -