RESUMO
AIM: This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. METHODS AND RESULTS: Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time-kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 µg ml-1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time-kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. CONCLUSION: Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR-FLU microparticles in formulations have potential as antifungal therapy.
Assuntos
Berberina , Candidíase , Humanos , Feminino , Fluconazol/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Berberina/farmacologia , Saliva Artificial/farmacologia , Saliva Artificial/uso terapêutico , Cremes, Espumas e Géis Vaginais/farmacologia , Cremes, Espumas e Géis Vaginais/uso terapêutico , Candidíase/microbiologia , Candida albicans , Testes de Sensibilidade Microbiana , Alginatos/farmacologia , Sinergismo Farmacológico , Farmacorresistência FúngicaRESUMO
Vaginal tolerance tests were performed with a new potential microbicidal and spermicidal product, an acid-buffering vaginal gel (Acidform) without or with nonoxynol-9 (N-9). The potential advantages over other vaginal products include keeping a low pH, decrease of the irritating effect of N-9 on the cervix or vaginal mucosa associated with greater retention of the product after application, and decreasing "messiness" as compared to other vaginal products. Three groups of six women were admitted and randomly assigned to use Acidform with 0%, 2.5%, and 5% N-9. Colposcopic evaluation for vulvar, vaginal, and cervical signs of irritation was performed and photographs were taken, following a specific World Health Organization protocol, at time 0, and after 24 h and 6 days of application of the gel. No irritation or symptom was reported by users of Acidform without N-9. A generalized and intense erythema in cervix was observed in 10 of 12 Acidform/N-9 users and abrasion occurred in nine of them. Vulvar irritation was seen in seven of these 10 volunteers. N-9 concentration in the gel (2.5% or 5.0%) was not related to the findings. No ulcer, exulceration, or de-epithelialization was observed. Acidform without N-9 was well tolerated by volunteers, but it was unable to protect the cervix, vagina, and vulva from the N-9 effects.