Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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.
Biomaterials. 2023 Oct;301:122260. doi: 10.1016/j.biomaterials.2023.122260. Epub 2023 Aug 3.
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.
全球有 2000 万感染艾滋病毒的青春期女孩和年轻女性，她们获得长效、有效、由女性控制的预防方法的机会有限。此外，尽管有许多避孕方法可用，但全球仍有一半的怀孕是意外怀孕。在这里，我们报告了第一个用于预防艾滋病毒和避孕的 3D 打印多用途预防技术（MPT）阴道环（IVR）。我们利用连续液界面生产（CLIP™）技术，在一种生物相容性的硅基树脂中制造 MPT IVR。依托孕诺酮（ENG）、乙炔雌二醇（EE）和伊斯拉韦林（ISL）通过吸收在受控的单一药物加载过程中被加载到硅酮聚（氨酯）IVR 中。ENG/EE/ISL IVR 在体外持续释放药物 150 天，在绵羊体内持续释放药物 14 天。在绵羊中评估的宫颈阴道毒性或阴道活检或微生物组群落特征的任何与 MPT IVR 相关的不良变化均未发现。此外，在恒河猴中，ISL IVR 能持续释放 28 天，ISL-三磷酸水平高于 50-100 fmol/10 PBMCs 的既定药代动力学基准。ISL IVR 在恒河猴中安全且耐受性良好，未观察到粘膜细胞因子变化或外周 CD4 T 细胞群的改变。总的来说，拟议的 MPT IVR 有可能为年轻女性扩大预防选择。
