Prolonged release and antiviral efficacy of HIV fusion inhibitor LP-98-loaded microspheres in rhesus macaques

作者：Zhe Cong, Yi Wei, Huihui Chong, Dong Zhang, Ling Tong, Jingjing Zhang, Yuanmei Zhu, Zejing Gao, Huijuan Jin, Jiahan Lu, Qiuhan Lu, Ting Chen, Qiang Wei, Guanghui Ma, Yuxian He, Fangling Gong, Jing Xue · 发表于：Journal of Controlled Release · 年份：2024 · DOI：10.1016/j.jconrel.2024.10.018 · 被引用次数：3 · 研究领域：HIV/AIDS Research and Interventions、HIV Research and Treatment、HIV-related health complications and treatments

Non-adherence to antiretroviral treatment is a critical obstacle to effectively managing the progression of AIDS and reducing transmission and mortality rates. A promising strategy to address the clinical disadvantages of user-dependent dosing and decrease medication frequency is the development of long-acting antiretrovirals. In this study, we fabricated PLGA microspheres (MS) incorporating the lipopeptide LP-98 (LP-98-MS), which has previously exhibited potent anti-HIV efficacy. Our findings demonstrate that a single-dose injection of LP-98-MS in SHIV-infected rhesus macaques resulted in sustained and gradual release, maintaining antiviral effects at least 28 days. Notably, a single administration of LP-98-MS provided more than 28 days of sustained release, resulting in high-level pre-exposure prophylaxis (PrEP) for rhesus macaques, even providing complete protection when exposed to repeated intravaginal and intrarectal SHIV challenges. Overall, LP-98-MS holds significant potential in reducing medication frequency and shows promising prospects for further development. • Uniform-sized PLGA MS loading lipopeptide LP-98 was fabricated monthly injection. • LP-98-MS exhibited gradual and sustained release for at least 28 days in vivo . • A single-dose of LP-98-MS sustained long-acting anti-SHIV suppression in macaques. • LP-98-MS provided high-level PrEP for a month against SHIV challenges in macaques.