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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: FRONTIERS IN MICROBIOLOGY; v. 10, JAN 10 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/19374-9 - Echinocandins in the control of infections associated to polymicrobial biofilms of Candida spp. and bacteria such as Stapholococcus aureus and Pseudomonas aeruginosa
• Grantee: Kelly Ishida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/07993-0 - ENCAPSULATION OF MILTEFOSINE INTO MICROPARTICLES OF ALGINATE AND EVALUATION OF EFFECTS "IN VITRO" AND "IN VIVO" ON MURINE MODEL OF PULMONARY CRYPTOCOCCOSIS
• Grantee: Kelly Ishida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2