Anti-HIV/AIDS vaginal prophylactic nanoparticle delivery system development research done using PolySciTech’s PLGA-Fluorescein

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers. One type of polymer is fluorescein-conjugated PLGA Mn: 20-40K (E.G. PolyVivo AV004) which is a useful polymer for tracking biodegradable systems such as nanoparticles by fluorescence techniques. Recently, researchers in Portugal used this polymer to generate traceable nanoparticles containing anti-retroviral drugs (efavirenz and tenofovir) for incorporation into a thin film as part of vaginal prophylactic against HIV-AIDS. They traced genital distribution as well as delivery and pharmacokinetics of the antiretroviral agents in a mouse model. This research holds promise to provide for a new tool in limiting the transmission of this deadly disease. Read more: Cunha-Reis, Cassilda, Alexandra Machado, Luísa Barreiros, Francisca Araújo, Rute Nunes, Vítor Seabra, Domingos Ferreira, Marcela A. Segundo, Bruno Sarmento, and José das Neves. "Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs." Journal of Controlled Release (2016). http://www.sciencedirect.com/science/article/pii/S0168365916307891

“Abstract: 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. 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. Chemical compounds studied in this article Efavirenz (PubChem CID: 64139); Hypromellose (PubChem CID: 57503849); Tenofovir (PubChem CID: 464205) Keywords HIV/AIDS; Nanotechnology; Pharmacokinetics; Pre-exposure prophylaxis; Safety; Vaginal drug administration”