Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations.

Curley, Paul, Hobson, James J ORCID: 0000-0003-2551-1774, Liptrott, Neill J ORCID: 0000-0002-5980-8966, Makarov, Edward, Al-Khouja, Amer, Tatham, Lee ORCID: 0000-0001-9448-8876, David, Christopher AW ORCID: 0000-0001-8504-2354, Box, Helen, Neary, Megan ORCID: 0000-0002-4960-2139, Sharp, Joanne
et al (show 7 more authors) (2023) Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations. Pharmaceutics, 15 (7). p. 1835.

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Long-acting injectable (LAI) formulations promise to deliver patient benefits by overcoming issues associated with non-adherence. A preclinical assessment of semi-solid prodrug nanoparticle (SSPN) LAI formulations of emtricitabine (FTC) is reported here. Pharmacokinetics over 28 days were assessed in Wistar rats, New Zealand white rabbits, and Balb/C mice following intramuscular injection. Two lead formulations were assessed for the prevention of an HIV infection in NSG-cmah<sup>-/-</sup> humanised mice to ensure antiviral activities were as anticipated according to the pharmacokinetics. Cmax was reached by 12, 48, and 24 h in rats, rabbits, and mice, respectively. Plasma concentrations were below the limit of detection (2 ng/mL) by 21 days in rats and rabbits, and 28 days in mice. Mice treated with SSPN formulations demonstrated undetectable viral loads (700 copies/mL detection limit), and HIV RNA remained undetectable 28 days post-infection in plasma, spleen, lung, and liver. The in vivo data presented here demonstrate that the combined prodrug/SSPN approach can provide a dramatically extended pharmacokinetic half-life across multiple preclinical species. Species differences in renal clearance of FTC mean that longer exposures are likely to be achievable in humans than in preclinical models.

Item Type: Article
Uncontrolled Keywords: HIV, long-acting, pre-exposure prophylaxis, nano, emtricitabine
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 01 Aug 2023 10:08
Last Modified: 09 Aug 2023 23:46
DOI: 10.3390/pharmaceutics15071835
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