Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Cunha Reis, C (Autor) Outra; Machado, A (Autor) Outra; Barreiros, L (Autor) Outra; Araujo, F (Autor) Outra; Nunes, R (Autor) Outra; Seabra, V (Autor) Outra; Ferreira, DC (Autor) FFUP; Marcela A Segundo (Autor) FFUP; Sarmento, B (Autor) Outra; das Neves, J (Autor) Outra

Revista

Título: Journal of Controlled Release

Vol. 243

Páginas: 43-53

ISSN: 0168-3659

Editora: Elsevier

Indexação

ISI Web of Knowledge - 30 Citações

Scopus - 52 Citações

Outras Informações

ID Authenticus: P-00M-4F6

DOI: 10.1016/j.jconrel.2016.09.020

Abstract (EN): Combining two or more antiretroviral drugs in one medical product is an interesting but challenging strategy for developing topical anti-HIV microbicides. We developed a new vaginal delivery system comprising the incorporation of nanoparticles (NPs) into a polymeric film base - NPs-in-film - and tested its ability to deliver tenofovir (TFV) and efavirenz (EFV). EFV-loaded poly(lactic-co-glycolic acid) NPs were incorporated alongside free TFV into fast dissolving films during film manufacturing. The delivery system was characterized for physicochemical properties, as well as genital distribution, local and systemic 24 h pharmacokinetics (PK), and safety upon intravaginal administration to mice. NPs-in-film presented suitable technological, mechanical and cytotoxicity features for vaginal use. Retention of NPs in vivo was enhanced both in vaginal lavages and tissue when associated to film. PK data evidenced that vaginal drug levels rapidly decreased after administration but NPs-in-film were still able to enhance drug concentrations of EFV. Obtained values for area-under-the-curve for EFV were around one log10 higher than those for the free drugs in aqueous vehicle (phosphate buffered saline). Film alone also contributed to higher and more prolonged local drug levels as compared to the administration of TFV and EFV in aqueous vehicle. Systemic exposure to both drugs was low. NPs-in-film was found to be safe upon once daily vaginal administration to mice, with no significant genital histological changes or major alterations in cytokine/chemokine profiles being observed. Overall, the proposed NPs-in-film system seems to be an interesting delivery platform for developing combination vaginal anti-HIV microbicides.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11