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<p>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 <i>Candida albicans</i> and non<i>-albicans</i> (NAC). The ovules were produced with a hydrophobic and low molecular weight ureasil-polyether through the sol–gel process. <sup>1</sup>H 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&#xa0;µg/mL can negatively affect the vaginal microbiota. U-PPO400 had no impact on the growth of <i>Lactobacillus jensenii</i>. The cytotoxicity of the drugs on VK2/E6E7 vaginal epithelial cells was observed at concentrations equal to or greater than 5.94&#xa0;µg/mL for MCZ and 256&#xa0;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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年5月28日

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  • Brenda Maria Silva Bezerra,
  • Kaidy G. Orellana,
  • Chen Sun,
  • Karina Guimarães Lima,
  • Emmanuel A. Ho,
  • João Augusto Oshiro-Junior

摘要

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.

Graphical Abstract