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.
|
Text
pharmaceutics-15-01835.pdf - Open Access published version Download (2MB) | Preview |
Abstract
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 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3172013 |
Dimensions
Dimensions
