Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies



Hobson, James ORCID: 0000-0003-2551-1774, Al-Khouja, Amer, Curley, Paul ORCID: 0000-0003-4596-2708, Meyers, David, Flexner, Charles, Siccardi, Marco ORCID: 0000-0002-3539-7867, Owen, Andrew ORCID: 0000-0002-9819-7651, Freel Meyers, Caren and Rannard, SP ORCID: 0000-0002-6946-1097
(2019) Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies. Nature Communications, 10.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Diseases, Drug delivery, Drug discovery, Infectious diseases, Pharmacology
Depositing User: Symplectic Admin
Date Deposited: 12 Mar 2019 09:34
Last Modified: 06 Oct 2021 19:18
DOI: 10.1038/s41467-019-09354-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3034105