The increasing global prevalence of human immunodeficiency virus (HIV) is estimated at 36.7 million people currently infected. Lifelong antiretroviral (ARV) drug combination dosing allows management as a chronic condition by suppressing circulating viral load to allow for a near-normal life; however, the daily burden of oral administration may lead to non-adherence and drug resistance development. Long-acting (LA) depot injections of nanomilled poorly water-soluble ARVs have shown highly promising clinical results with drug exposure largely maintained over months after a single injection. ARV oral combinations rely on water-soluble backbone drugs which are not compatible with nanomilling. Here, we evaluate a unique prodrug/nanoparticle formation strategy to facilitate semi-solid prodrug nanoparticles (SSPNs) of the highly water-soluble nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (FTC), and injectable aqueous nanodispersions; in vitro to in vivo extrapolation (IVIVE) modelling predicts sustained prodrug release, with activation in relevant biological environments, representing a first step towards complete injectable LA regimens containing NRTIs.

据估计，目前全球有 3670 万人感染了人类免疫缺陷病毒 (HIV)，全球流行率不断增加。终生抗逆转录病毒 (ARV) 药物组合给药允许通过抑制循环病毒载量以允许接近正常的生活作为慢性病进行管理；然而，口服给药的日常负担可能导致不依从性和耐药性的发展。纳米研磨难溶性 ARV 的长效 (LA) 长效 (LA) 长效注射剂已显示出非常有希望的临床结果，单次注射后药物暴露基本维持数月。ARV 口服组合依赖于与纳米研磨不兼容的水溶性骨架药物。这里，我们评估了一种独特的前药/纳米颗粒形成策略，以促进高水溶性核苷逆转录酶抑制剂 (NRTI) 恩曲他滨 (FTC) 和可注射水性纳米分散体的半固体前药纳米颗粒 (SSPN)；体外到体内外推 (IVIVE) 模型预测持续的前药释放，并在相关生物环境中激活，代表朝着包含 NRTI 的完整可注射 LA 方案迈出的第一步。