Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies
Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies
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DOI：
10.1038/s41467-019-09354-z
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发表时间：
2019-03-29
影响因子：
16.6
通讯作者：
Rannard, Steve P.
中科院分区：
文献类型：
--
作者：
Hobson, James J.;Al-Khouja, Amer;Rannard, Steve P.
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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.