Abstract：
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.
摘要：
外阴阴道念珠菌病（VVC）是由念珠菌属真菌引起的机会性感染，影响了大约75%的女性一生。真菌耐药性病例和不良反应一直是口服疗法的主要挑战。在这项研究中,建议局部应用含有氟康唑（FLU）和百里酚（THY）的薄膜来克服这些问题。通过溶剂流延法开发了仅基于壳聚糖（CH）或将该生物聚合物与果胶（PEC）或醋酸羟丙基甲基纤维素琥珀酸酯（HPMCAS）结合的阴道膜。除了较高的溶胀指数，CH/HPMCAS膜显示比用CH/PEC或仅壳聚糖制备的系统更具可塑性和柔韧性。发现生物聚合物和FLU处于无定形状态，有助于解释与阴道液接触后迅速形成凝胶。FLU固定到薄膜中后也发现了高渗透率。聚合物膜中THY的存在增加了FLU在阴道组织中的分布，并导致抗念珠菌活性的提高。实现了对抗性光滑梭菌的显著活性，将所需的FLU剂量减少50%。这些结果表明，开发的聚合物薄膜代表了一种有希望的替代治疗耐药性外阴阴道念珠菌病。鼓励在这方面进行进一步的研究。
