Nanocarriers Provide Sustained Antifungal Activity for Amphotericin B and Miltefosine in the Topical Treatment of Murine Vaginal Candidiasis

Autor(es)

Mendes da Silva de Bastiani, Fernanda Walt ^[1] ; Spadari, Cristina de Castro ^[1] ; Rocha de Matos, Jenyffer Kelly ^[2] ; Salata, Giovanna Cassone ^[2] ; Lopes, Luciana Biagini ^[2] ; Ishida, Kelly ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Antifungal Chemotherapy, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Nanomed & Drug Delivery Syst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 10, JAN 10 2020.
• Citações Web of Science: 0

Resumo

Topical drug administration is frequently used for the treatment of vaginal candidiasis; however, most formulations using this route do not provide prolonged drug release. Our aim was to evaluate the antifungal efficacy of amphotericin B (AMB) and miltefosine (MFS) incorporated in nanocarriers for sustained drug release, in a murine model of vaginal candidiasis. AMB and MFS were incorporated in different topical formulations, namely: conventional vaginal cream (daily dose for 6 days; MFS-CR and AMB-CR groups), microemulsion that transforms into a liquid crystalline gel in situ (single dose, or in three doses, every 48 h; AMB-ME and MFS-ME groups) and alginate nanoparticles (single dose; MFS-AN group). Formulations were administered intravaginally in BALB/c female mice 24 h post-infection by Candida albicans yeasts. On the 7th day post-infection the animals were euthanized for mycological and histological analyses. Formulation persistence in the vaginal canal was assessed for 7 days by in vivo imaging, using nanocarriers labeled with Alexa-Fluor 647. AMB-ME(3x), MFS-ME(3x), and MFS-AN(1x) formulations were able to control fungal infection at comparable levels to those vaginal cream formulations. Notably, a single dose of MFS-AN was sufficient to reduce the fungal burden as effectively as MFS-ME(3x) and MFS-CR(6x). In vivo imaging showed that nanocarriers allowed prolonged antifungal activity by intravaginal administration reducing drug administration frequency. Therefore, AMB and MFS incorporated into a microemulsion and MFS encapsulated in alginate nanoparticles could be effective therapeutic alternatives for vaginal candidiasis, likely due to the sustained antifungal activity provided by these nanocarriers. (AU)

• Processo FAPESP: 17/19374-9 - Equinocandinas no controle de infecções associadas a biofilmes polimicrobianos de Candida spp. e bactérias como Stapholococcus aureus e Pseudomonas aeruginosa
• Beneficiário: Kelly Ishida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/07993-0 - Encapsulamento da miltefosina em micropartículas de alginato e avaliação dos efeitos "in vitro" e "in vivo" em modelo murino de criptococose pulmonar
• Beneficiário: Kelly Ishida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/13877-1 - Nanocarreadores para a quimioprevenção e tratamento localizado de tumores de mama
• Beneficiário: Luciana Biagini Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2