RESUMO
Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.
Assuntos
Antifúngicos , Candidíase Vulvovaginal , Fluconazol , Timol , Feminino , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Fluconazol/farmacologia , Fluconazol/química , Fluconazol/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/administração & dosagem , Biopolímeros/química , Timol/química , Timol/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Humanos , Quitosana/química , Testes de Sensibilidade Microbiana , Animais , Portadores de Fármacos/química , Permeabilidade , Candida glabrata/efeitos dos fármacosRESUMO
Among the strategies to improve the biopharmaceutic properties of poorly soluble drugs, Supersaturating Drug Delivery Systems like polymer-based amorphous solid dispersions (SD) have been successfully applied. The screening of appropriate polymeric carriers to compose SD is a crucial point on their development. In this study, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS) types L, M and H and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL) were evaluated by in vitro supersaturation studies regarding their anti-precipitant ability on the poorly soluble drug candesartan cilexetil (CC) under two different media, including biorelevant conditions. According to the results, HPMCAS M was considered the best carrier to develop SD containing CC among all the polymers tested, due to its good anti-precipitant performance in both media. In addition, the medium used in the in vitro supersaturation studies played an important role on the results, and its selection should be carefully done.