Salmazi Rafael, Calixto Giovana, Bernegossi Jéssica, Ramos Matheus Aparecido dos Santos, Bauab Taís Maria, Chorilli Marlus
School of Pharmaceutical Sciences, UNESP - Sao Paulo State University, Campus Araraquara, Department of Drugs and Medicines, Araraquara, Sao Paulo, Brazil.
Int J Nanomedicine. 2015 Jul 30;10:4815-24. doi: 10.2147/IJN.S82385. eCollection 2015.
Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis.
女性常发生主要由念珠菌属微生物引起的阴道感染。目前，阴道念珠菌病的治疗通常涉及基于唑类的抗真菌药物，尽管真菌对这些化合物的耐药性已很普遍。因此，人们对来自天然来源的具有抗真菌特性的分子给予了很多关注，比如姜黄素（CUR）。然而，CUR在水性溶剂中的溶解度差，口服生物利用度也低。本研究试图通过开发、表征和评估用于阴道给药的载CUR液晶前体粘膜粘附系统（LCPM）的体外抗真菌作用来克服这一问题。开发了一种低粘度LCPM（F），其由40%重量/重量的聚氧丙烯-（5）-聚氧乙烯-（20）-鲸蜡醇、50%重量/重量的油酸和10%重量/重量的0.5%壳聚糖分散体，并添加16%泊洛沙姆407，以利用该制剂的溶致相行为。值得注意的是，当用人工阴道粘液以1:3和1:1（重量/重量）的比例稀释时，F可分别转化为液晶系统，分别形成F30和F100。偏光显微镜和流变学研究表明，F表现为各向同性制剂，而F30和F100表现为各向异性液晶系统（LCS）。此外，F30和F100对猪阴道粘膜的粘膜粘附性高于F。对白色念珠菌的体外活性分析表明，与CUR溶液相比，载CUR的F对标准菌株和临床菌株更有效。因此，阴道给药载CUR的LCPM代表了一种治疗阴道念珠菌病的有前景的平台。
