Transfersomal nanocarriers of nystatin for treating VVC

Ossama Sayed, PharmD, PhD

“A notable increase in VVC infestation cases has been reported by local gynecologists,” said principal investigator Ossama Sayed, PharmD, PhD, an associate professor of pharmaceutics at Sinai University, Kantara branch, Ismaelia, Egypt. “In fact, we conducted a survey of around 100 clinics to confirm this finding.”

The study prepared and evaluated nystatin-loaded transfersomes designed to achieve better treatment outcomes for VVC.

“For many decades now, nystatin has been used as a broad-spectrum antifungal agent for eradicating superficial candida infestation such as VVC because of its fungicidal effect,” Sayed told Contemporary OB/GYN®. “Nystatin’s mechanism of action is dependent on the formation of pores in the plasma membrane of antibiotic sensitive organisms by attaching to ergosterol.”

The study formulated nystatin transferosomes by the thin-film hydration method.

“A 32 full factorial design was employed to evaluate the effect of nine different formulations,” Sayed said.

2 independent variables were chosen—the ratio between a lecithin surfactant set at 3 levels (between 10 and 40)—and the type of surfactant set at 3 levels (Span 60, Span 85 and Pluronic F-127).

The 3 dependent responses were entrapment efficiency, vesicles size and release rate.

The vesicles attained high nystatin encapsulation efficiency, ranging from 97.35% (± 0.03%) to 98.01% (± 0.20%), whereas vesicle size ranged from 194.8 nm (± 20.42 nm) to 400.8 nm (± 42.09 nm).

Large negative zeta potential values also revealed good stability of the prepared formulations.

“Nystatin release from transfersomes was biphasic and the release pattern followed the Higuchi model for the rate of drug release from matrix devices,” Sayed said. “The sustained release of nystatin from the developed transfersomes was up to 24 hours.”

The authors chose the formulation F7 as the optimum transfersomal formulation for further investigation because it exhibited spherical morphology under transmission electron microscopy.

“Both in-vitro and in-vivo antifungal efficiency studies have concluded that the optimized formula F7 exhibits significant eradication of candida infestation in comparison to free nystatin,” Sayed said.

The current study tested the effectiveness of F7 and free drug suspension on candida infestation in albino female mice compared to a positive control group (infested without treatment). After 48 and 96 hours, both the transfersomes formulation and the free drug suspension showed a significant reduction in candida colonies vs the positive control group (P < 0.05).

The results also revealed that F7 achieved higher candida eradication power than the free drug suspension (P < 0.05).

Based on study results, the developed nystatin transfersomes might be a promising drug delivery system to enhance the antifungal efficacy of nystatin.

“The expected clinical ramification of the study is focusing the spotlight on the reuse of classical active pharmaceutical ingredients (APIs) in nanocarriers for the treatment of different infestation cases,” Sayed said. “Reuse of these drugs loaded on new nanocarriers could lead to new indications and fewer side effects. This could save a lot of money spent on synthesis of new APIs.”

Reference

1. Hady MA, Darwish AB, Abdel-Aziz MS, et al.Design of transfersomal nanocarriers of nystatin for combating vulvovaginal candidiasis: a different prospective. Colloids Surf B Biointerfaces. Published online December 23, 2021. doi.org/10.1016/j.colsurfb.2021.112304