Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Control Release. 2023 Nov;363:606-620. doi: 10.1016/j.jconrel.2023.10.006. Epub 2023 Oct 12.
Only condoms are proven to protect against both HIV and unplanned pregnancy, however, poor user acceptability and lack of partner cooperation impede effectiveness. We developed an injectable ultra-long-acting, biodegradable, and removable in-situ forming implant (ISFI) as multipurpose prevention technology (MPT). MPT ISFIs co-formulated an antiretroviral (dolutegravir (DTG)) or cabotegravir (CAB)), and a hormonal contraceptive (etonogestrel (ENG) or medroxyprogesterone acetate (MPA)). All formulations were well-tolerated in mice with no signs of chronic local or systemic inflammation. Plasma CAB and DTG concentrations were above 4× PA-IC for 90 days with zero-order and diffusion-controlled absorption, respectively, and no differences when co-formulated with either hormone. Plasma ENG and MPA concentrations were quantifiable for 90 days. Complete removal of CAB/MPA ISFIs resulted in MPA concentrations falling below the limit of quantification after 24 h post-removal, but incomplete CAB elimination from plasma. Collectively, we demonstrated the ability to co-formulate antiretrovirals with contraceptives in an ISFI that is well-tolerated with sustained plasma concentrations up to 90 days.
只有避孕套被证明既能预防 HIV 又能预防意外怀孕，然而，较差的用户接受度和缺乏伴侣合作阻碍了其效果。我们开发了一种可注射的超长效、可生物降解和可移除的原位形成植入物（ISFI）作为多用途预防技术（MPT）。MPT ISFI 共同配制了一种抗逆转录病毒药物（多替拉韦（DTG）或卡替拉韦（CAB））和一种激素避孕药（依托孕烯（ENG）或醋酸甲羟孕酮（MPA））。所有配方在小鼠中均耐受良好，没有慢性局部或全身炎症的迹象。CAB 和 DTG 的血浆浓度分别以零级和扩散控制吸收的方式超过 90 天的 4×PA-IC，与两种激素共同配制时没有差异。ENG 和 MPA 的血浆浓度可在 90 天内定量。完全去除 CAB/MPA ISFI 会导致 MPA 浓度在去除后 24 小时内降至定量下限以下，但 CAB 不能从血浆中完全消除。总的来说，我们证明了能够在 ISFI 中共同配制抗逆转录病毒药物和避孕药，该 ISFI 具有良好的耐受性，血浆浓度可持续长达 90 天。
