Enhanced efficacy of hybrid vaginal ovules against Candida albicans


A new study revealed that hybrid vaginal ovules, incorporating curcumin and miconazole nitrate, offer effective relief against Candida albicans, potentially revolutionizing treatment for vulvovaginal candidiasis with reduced dosing frequency and adverse effects.

Enhanced efficacy of hybrid vaginal ovules against Candida albicans | Image Credit: © Jezper - © Jezper - stock.adobe.com.

Enhanced efficacy of hybrid vaginal ovules against Candida albicans | Image Credit: © Jezper - © Jezper - stock.adobe.com.

Hybrid vaginal ovules are effective against Candida albicans when administered at a lower frequency and dose compared to current formulations, according to a recent study published in Pharmaceutics.


  1. The study investigates hybrid vaginal ovules combining curcumin and miconazole nitrate as a potential treatment for vulvovaginal candidiasis (VVC) caused by Candida albicans.
  2. Results suggest that these hybrid ovules may require lower doses and less frequent administration compared to current formulations, promising improved patient compliance and reduced adverse effects.
  3. The ovules leverage the antifungal potential of curcumin, a polyphenol, combined with the drug miconazole nitrate. This combination aims to enhance clinical efficacy against VVC.
  4. Utilizing a ureasil–poly (ethylene oxide) (U-PEO) matrix for drug delivery, the study introduces a controlled-release mechanism, ensuring a prolonged and sustained release of curcumin and miconazole nitrate.
  5. Thermal analysis indicates that the drugs exhibit greater stability when incorporated into the U-PEO matrix. Moreover, the release profile shows a prolonged release of both curcumin and miconazole nitrate from the ovules, promising sustained therapeutic effects.

Shifts in the microenvironment and microbiota of the vaginal mucosa may cause C. albicans fungus to grow pathogenically, leading to vulvovaginal candidiasis (VVC). Seventy percent of reproductive aged women experience VVC at least once in their lifetime, leading to inflammatory symptoms associated with significant discomfort.

VVC is often treated with azole antifungal agents, but this treatment is associated with contraindications to pregnancy and adverse vaginal and gastrointestinal outcomes. Combined therapy may be an effective alternative treatment because of increased fungicidal activity, reducing doses and adverse effects.

Curcumin (CUR) is a polyphenol with antifungal potential. When combined with the antifungal drug miconazole nitrate (MCZ) against VVC, it may improve clinical efficacy.Additionally, a controlled release system may reduce issues from administering CYR and MCZ caused by their low water solubility.

Investigators conducted a study evaluating the efficacy of ureasil–poly (ethylene oxide) (U-PEO) vaginal ovules loaded with CUR and MCZ against VVC caused by C. albicans. The sol-gel method was utilized to obtain a hybrid precursor, with a molecular mass of 500 g·mol−1.

The ovules were formed through hydrolysis and condensation reaction using 5 g of precursor, 2000 µL ethanol, 300 µL water, and 80 µL of the catalyst agent. CUR and MCZ were incorporated at a ratio of 2.7% and dissolved in a solution of ethanol and water.

A simultaneous thermal analyzer (ShimadzuTM-DTG-60, Shimadzu, Kyoto, Japan) was used to obtain thermogravimetry (TGA) curves for CUR, MCZ, and U-PEO, while a simultaneous thermal analyzer (ShimadzuTM-DTG-60) was used to obtain differential thermal analysis curves.

An infrared spectrometer (Spectrum 400-Perkin Elmer, Norwalk, CA, USA) with a wavenumber range between 4000 and 650 cm−1 was used to obtain Fourier transform infrared spectra.

Ovules were evaluated in 900 mL acetate buffer pH 4.2 plus 15% Tween 80 and 5% absolute ethanol to determine CUR release. MCZ release was determined by assessing ovules in 200 mL acetate buffer pH 4.2 with 5% sodium lauryl sulfate. The broth microdilution checkerboard method was used to evaluate the interaction between CUR and MCZ.

The minimum inhibitory concentration (MIC) of CUR and MCZ were also determined to assess antifungal activity. The broth microdilution method was utilized to determine MICs. In comparison, the antifungal activity of U-PEO ovules was assessed using broth microdilution and agar diffusion.

U-PEO vaginal ovules were transparent and homogenous. No cracks or fissures were observed after drying. This indicated they would be well-received by the intended audiences.

The use of cold-molding when making U-PEO eliminated potential errors that occur during traditional drug production. High quantities can be obtained through hydrolysis and condensation reactions.

There were 3 stages of thermal decomposition shown in the TGA curve of U-PEO. The first had a mass loss of 7.54%, the second a mass loss of 56.24%, and the third a mass loss of 12.78%.Decomposition of U-PEO was not complete based on a 23.44% residue in the N2 flow atmosphere.

For CUR, 2 thermal events were observed, with mass losses of 56.01% and 16.03%. A residue of 26.28% indicated incomplete thermal decomposition. MCZ had 3 stages of decomposition, with mass losses of 20.49%, 65.72%, and 10.01%. Additionally, MCZ almost entirely decomposed into CO2, NO, and CO gases.

In a binary mixture of CUR and MCZ, 2 thermal events occurred, with mass losses of 47.58% and 29.27%. A final residue of 23.14% was reported. When loading U-PEO with CUR and MCZ, there were 3 thermal events. Both drugs had greater thermal stability after incorporation into U-PEO.

In 24 hours, 42% of CUR was released, and a plateau of 81% was seen after 120 hours. Similar trends were observed for MCZ, with 57% released in the first 24 hours and a plateau of 95% at 144 hours. This indicated a prolonged release profile of CUR and MCZ from U-PEO.

These results indicated efficacy from a vaginal ovule combining CUR and MCZ against VVC caused by C. albicans. Investigators recommended further research to confirm these results.


Bezerra BMS, Y Araújo SEDM, Alves-Júnior JO, Damasceno BPGL, Oshiro-Junior JA. The efficacy of hybrid vaginal ovules for co-delivery of curcumin and miconazole against Candida albicans. Pharmaceutics. 2024;16(3):312. doi:10.3390/pharmaceutics16030312

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