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Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs.
J Control Release. 2016 12 10; 243:43-53.JC

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 24h 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.

Authors+Show Affiliations

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal.i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal.Laboratório de Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal. Electronic address: j.dasneves@ineb.up.pt.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27664327

Citation

Cunha-Reis, Cassilda, et al. "Nanoparticles-in-film for the Combined Vaginal Delivery of anti-HIV Microbicide Drugs." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 243, 2016, pp. 43-53.
Cunha-Reis C, Machado A, Barreiros L, et al. Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. J Control Release. 2016;243:43-53.
Cunha-Reis, C., Machado, A., Barreiros, L., Araújo, F., Nunes, R., Seabra, V., Ferreira, D., Segundo, M. A., Sarmento, B., & das Neves, J. (2016). Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. Journal of Controlled Release : Official Journal of the Controlled Release Society, 243, 43-53. https://doi.org/10.1016/j.jconrel.2016.09.020
Cunha-Reis C, et al. Nanoparticles-in-film for the Combined Vaginal Delivery of anti-HIV Microbicide Drugs. J Control Release. 2016 12 10;243:43-53. PubMed PMID: 27664327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. AU - Cunha-Reis,Cassilda, AU - Machado,Alexandra, AU - Barreiros,Luísa, AU - Araújo,Francisca, AU - Nunes,Rute, AU - Seabra,Vítor, AU - Ferreira,Domingos, AU - Segundo,Marcela A, AU - Sarmento,Bruno, AU - das Neves,José, Y1 - 2016/09/21/ PY - 2016/07/01/received PY - 2016/09/15/revised PY - 2016/09/20/accepted PY - 2016/11/5/pubmed PY - 2017/12/28/medline PY - 2016/11/7/entrez KW - Efavirenz (PubChem CID: 64139) KW - HIV/AIDS KW - Hypromellose (PubChem CID: 57503849) KW - Nanotechnology KW - Pharmacokinetics KW - Pre-exposure prophylaxis KW - Safety KW - Tenofovir (PubChem CID: 464205) KW - Vaginal drug administration SP - 43 EP - 53 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 243 N2 - 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 24h 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. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/27664327/Nanoparticles_in_film_for_the_combined_vaginal_delivery_of_anti_HIV_microbicide_drugs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(16)30789-1 DB - PRIME DP - Unbound Medicine ER -