Nanoparticles effective at treating vulvovaginal candidiasis

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According to a recent study published in the European Journal of Pharmaceutical Sciences, vulvovaginal candidiasis (VVC) may be effectively treated using miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA).

About 70% to 75% of reproductive-aged women experience VVC, presenting as vulva or vaginal inflammation. Recurrent VVC (RVCC), defined as 4 or more symptomatic episodes within 12 months, occurs in 40% to 50% of women who experience VVC. About 138 million women per year are affected by RVCC.

Clinical symptoms of VVC and RVCC include vaginal discharge, vulvar erythema, vulvovaginal pruritus, oedema, and soreness. Over 90% of VVC episodes are caused by the Candida albicans (C. albicans). Infections by the Candida species may be caused by the intestine, sexual activity, or remained yeasts. Augmented estrogen levels also increase VVC risk.

Antifungal drugs including imidazoles, triazoles, polyenes, and ciclopirox olamine are used to treat VVC. However, dosage regimens are complex, last months, and have high recurrence rates.

Scientists developed antifungal drug delivery systems for VVC and RVCC treatment to overcome barriers on pharmaceutical therapies. This includes miconazole-loaded nanoparticles/HA, which are employed to suppress the C. Albicans. Investigators conducted a study todetermine the efficacy of this treatment.

Emulsification and solvent evaporation techniques were modified for preparing uncoated miconazole-loaded nanoparticles. Miconazole concentrations of 0.5 mg mL-1 and 1 mg mL-1, along with PCL masses of 25.9 mg and 36 mg, were used to synthesize 4 total formulations.

To produce miconazole-loaded nanoparticles/HA, investigators first ultracentrifuged uncoated nanoparticles at 14 g for 30 minutes at 8 °C, then removed the supernatant. Afterward, investigators resuspended the pellet in 2 mL of purified water, then placed it in 5 mL of an aqueous solution with different concentrations of HA.

Photon Correlation Spectroscopy (Malvern S4700 PCS System, Malvern Instruments, UK) was used to measure mean nanoparticle diameter and polydispersity index, with zeta potential measured by electrophoretic mobility. Miconazole encapsulation efficiency was determined using a High-Performance Chromatographic (HPLC-UV, Waters, Milford, MA, EUA) method.

A standard buffer solution at pH 4, 7, and 9.2 was employed when measuring pH, with measurements occurring at 25 ± 1 °C. Thermal analysis was performed by drying uncoated and coated miconazole-loaded nanoparticlesat 25 °C, then keeping the nanoparticles in a dissector for 7 days.

Uncoated and coated nanoparticles underwent in vitro miconazole release for 96 hours under sink conditions. The HPLC method was used to measure the release of miconazole from nanoparticles.

A higher PCL mass led to nanoparticles with a diameter of 300 nitrogen mustards(nm) to 400 nm. A higher polymer mass also caused higher polydispersity indexes.

Lower diameter, polydispersity index, and zeta potential values were seen in nano-systems composed of a 25.9 mg PCL mass. Uncoated miconazole-loaded nanoparticles made with both drug concentrations and a lower PCL mass had a diameter of 200 nm.

Higher HA was associated with augmentation of diameter and polydispersity index. As this risked impacting the formulation’s physiochemical stability, only miconazole-loaded nanoparticles coated with 0.25% (w/v) HA were used for the remainder of the study.

When presenting pH measurements, investigators wrote, “the pH of uncoated miconazole-loaded nanoparticles and miconazole-loaded nanoparticles/HA in suspension was 4.64 ± 0.03 and 3.06 ± 0.01, respectively.”

Nanoparticles released about 36% of miconazole at 6 hours, 55% at 12 hours, and 100% at 72 hours. When evaluating the in vitro fungicidal activity against the C. albicans of uncoated miconazole-loaded nanoparticles, significant increases in inhibition zones induced by the pure drug were found compared to those gathered from nano-systems in all concentrations.

These results indicated efficacy from miconazole-loaded nanoparticles/HA in treating VVC. Miconazole-loaded nanoparticles/HA may be effective as an alternative local treatment for VVC and RVVC.

Reference

Don Reis Teixeira A, De Vasconcelos Quaresma A, Tupinambá Branquinho R, et al. Miconazole-loaded nanoparticles coated with hyaluronic acid to treat vulvovaginal candidiasis. European Journal of Pharmaceutical Sciences. 2023;188. doi:10.1016/j.ejps.2023.106508