p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis

Autor(es)

Ferreira, P. S. ^[1] ; Victorelli, F. D. ^[1] ; Rodero, C. F. ^[1] ; Fortunato, G. C. ^[2] ; Araujo, V. H. S. ^[1] ; Fonseca-Santos, B. ^[1] ; Bauab, T. M. ^[2] ; Van Dijck, P. ^{[3, 4]} ; Chorilli, M. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Drugs & Med, Araraquara, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP - Brazil

^[3] VIB KU Leuven Ctr Microbiol, Flanders - Belgium

^[4] Katholieke Univ Leuven, Lab Mol Cell Biol, Inst Bot & Microbiol, Leuven - Belgium

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Pharmaceutics; v. 603, JUN 15 2021.
• Citações Web of Science: 0

Resumo

Vulvovaginal candidiasis (VVC) is an extremely common type of vaginal infection, which is mainly caused by Candida albicans. However, non-albicans Candida species are frequently more resistant to conventional antifungal agents and can represent up to 30% of cases. Due to side effects and increasing antifungal resistance presented by standard therapies, phenolic compounds, such as p-coumaric acid (p-CA), have been studied as molecules from natural sources with potential antifungal activity. p-CA is a poorly water-soluble compound, thus loading it into liquid crystals (LCs) may increase its solubility and effectiveness on the vaginal mucosa. Thereby, here we propose the development of mucoadhesive liquid crystalline systems with controlled release of p-CA, for the local treatment of VVC. Developed LCs consisted of fixed oily and aqueous phases (oleic acid and cholesterol (5:1) and poloxamer dispersion 16%, respectively), changing only the surfactant phase components (triethanolamine oleate (TEA-Oleate) or triethanolamine (TEA), the latter producing TEA-Oleate molecules when mixed with oleic acid). Systems were also diluted in artificial vaginal mucus (1:1 ratio) to mimic the vaginal environment and verify possible structural changes on formulations upon exposure to the mucosa. From the characterization as-says, p-CA loaded TEA-Oleate systems presented mucoadhesive profile, liquid crystalline mesophases, well-organized structures and pseudoplastic behaviour, which are desirable parameters for topical formulations. Moreover, they were able to control the release of p-CA throughout the 12 h assay, as well as decrease its permeation into the vaginal mucosa. p-CA showed antifungal activity in vitro against reference strains of C. albicans (SC5314), C. glabrata (ATCC 2001) and C. krusei (ATCC 6258), and exhibited higher eradication of mature biofilms than amphotericin B and fluconazole. In vivo experiments demonstrated that the formulations reduced the presence of filamentous forms in the vaginal lavages and provided an improvement in swelling and redness present in the mice vaginal regions. Altogether, here we demonstrated the potential and feasibility of using p-CA loaded liquid crystalline systems as a mucoadhesive drug delivery system for topical treatment of VVC. (AU)

• Processo FAPESP: 19/10261-2 - Avaliação do potencial de carreadores lipídicos nanoestruturados para co-encapsulação de curcumina e fluconazol dispersos em hidrogéis termorreponsivos no tratamento de candidíase vulvovaginal
• Beneficiário: Victor Hugo Sousa Araujo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/22928-6 - Sistemas líquido-cristalinos como potencial estratégia para administração vaginal de ácido p-cumárico no tratamento de candidíase vulvovaginal
• Beneficiário: Paula Scanavez Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/10016-2 - Sistemas precursores de cristais líquidos como estratégia para administração vaginal do peptídeo CTT1: desenvolvimento farmacotécnico e potencial aplicação no tratamento do câncer cervical
• Beneficiário: Marlus Chorilli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/22658-1 - Sistemas líquido-cristalinos como estratégia para administração vaginal de ácido p-cumárico no tratamento da candidíase vulvovaginal: avaliação in vitro e in vivo
• Beneficiário: Paula Scanavez Ferreira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Mestrado