Ureasil-polyether hybrid polymer-based vaginal ovules for combination therapy in the treatment of vulvovaginal candidiasis

Abstract

The aim of this research was to develop, characterize and evaluate the biocompatibility of ureasil-poly(propylene oxide) (U-PPO400) vaginal ovules for the modified release of a natural polyphenolic compound and an azole agent in the treatment of vulvovaginal candidiasis (VVC) caused by Candida albicans and non-albicans (NAC). The ovules were produced with a hydrophobic and low molecular weight ureasil-polyether through the sol-gel process. ¹H NMR confirmed that the organic-inorganic molecule was obtained. X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed the presence of drug crystals in the ovules. Miconazole (MCZ) and curcumin (CUR) were released by 60.95% and 12.06% in six days, respectively. The synergistic and additive effect of the antifungals was confirmed in NAC strains, with minimum inhibitory concentrations of CUR and MCZ being reduced up to 16 and 8 times. Biocompatibility tests showed that MCZ concentrations higher than 90 µg/mL can negatively affect the vaginal microbiota. U-PPO400 had no impact on the growth of Lactobacillus jensenii. The cytotoxicity of the drugs on VK2/E6E7 vaginal epithelial cells was observed at concentrations equal to or greater than 5.94 µg/mL for MCZ and 256 µg/mL for CUR. No cytotoxic or inflammatory effects were observed after elution of the blank U-PPO400 ovules. This study demonstrated the biocompatibility and potential of the U-PPO400 base to promote controlled release of drugs and to reduce the frequency of use of vaginal ovules. The antifungal efficacy of the CUR/MCZ combination, especially against NAC strains, points to a promising alternative to improve the efficacy of the treatment of VVC.

Keywords: Controlled release; Non-albicans Candida; Organic–inorganic materials; Synergism; Vaginal drug delivery.