{"doi":"10.3390/pharmaceutics15071835","title":"Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations","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−/− 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.","journal":"Pharmaceutics","year":2023,"id":365744,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1121605,"name":"J. Hobson","orcid":"0000-0003-2551-1774","position":1,"is_corresponding":false},{"id":254190,"name":"Neill J. Liptrott","orcid":"0000-0002-5980-8966","position":2,"is_corresponding":false},{"id":396714,"name":"Edward Makarov","orcid":null,"position":3,"is_corresponding":false},{"id":1072598,"name":"Amer Al‐khouja","orcid":null,"position":4,"is_corresponding":false},{"id":254185,"name":"Lee Tatham","orcid":"0000-0001-9448-8876","position":5,"is_corresponding":false},{"id":254191,"name":"Christopher David","orcid":"0000-0001-8504-2354","position":6,"is_corresponding":false},{"id":256857,"name":"Helen Box","orcid":null,"position":7,"is_corresponding":false},{"id":254188,"name":"Megan Neary","orcid":"0000-0002-4960-2139","position":8,"is_corresponding":false},{"id":254189,"name":"Joanne Sharp","orcid":"0000-0001-8482-5736","position":9,"is_corresponding":false},{"id":256856,"name":"Henry Pertinez","orcid":null,"position":10,"is_corresponding":false},{"id":422617,"name":"David J. Meyers","orcid":"0000-0002-7010-6930","position":11,"is_corresponding":false},{"id":498021,"name":"Charles Flexner","orcid":"0000-0002-4495-5349","position":12,"is_corresponding":false},{"id":947220,"name":"Caren L. Freel Meyers","orcid":"0000-0003-1458-0897","position":13,"is_corresponding":false},{"id":395979,"name":"Larisa Y. Poluektova","orcid":"0000-0001-7339-8732","position":14,"is_corresponding":false},{"id":254192,"name":"Steve P. Rannard","orcid":"0000-0002-6946-1097","position":15,"is_corresponding":false},{"id":254201,"name":"Andrew Owen","orcid":"0000-0002-9819-7651","position":16,"is_corresponding":false},{"id":254187,"name":"Paul Curley","orcid":"0000-0003-4596-2708","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:14:50.885797Z","pmid":"37514020","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}