A novel nanotechnological mucoadhesive and fast-dissolving film for vaginal delivery of clotrimazole: design, characterization, and in vitro antifungal action

Drug Deliv Transl Res. 2022 Dec;12(12):2907-2919. doi: 10.1007/s13346-022-01154-1. Epub 2022 May 2.

Abstract

Pullulan (PUL) films containing pomegranate seed oil and Eudragit® RS100 nanocapsules loaded with clotrimazole (CTZ-NC-PUL) were developed to treat vulvovaginal candidiasis (VVC). Our findings showed that the nanocapsule average diameter was around 163 ± 4 nm, with polydispersity index values of up to 0.1 ± 0.01 and positively charged zeta potential (+ 43.5 ± 0.7 mV). The pH was in the acid range (5.14 ± 0.12) and encapsulation efficiency was around 99.6%; CTZ nanoencapsulation promoted higher homogeneity values for the film (91%), and the stability studies displayed no changes in the drug content after 120 days for the CTZ-NC-PUL under refrigerated conditions. All formulations were considered non-irritant, and CTZ-NC-PUL promoted a controlled release of the drug (60% in 24 h) compared to CTZ-PUL (100% in 8 h). The permeation results corroborate the drug release, where higher CTZ amounts were found in the mucosa and receptor medium for CTZ-PUL (21.02 and 4.46 μg/cm2). The films were fast dissolving (10 min), and CTZ-NC-PUL presented higher mucoadhesive properties; the antifungal activity against Candida albicans was maintained, and the in vitro efficacy of the film was proved. In conclusion, CTZ-NC-PUL formulation was considered promising and suitable for vaginal application against candida-related infections.

Keywords: Antifungal; Candidiasis; Fungal infections; Nanoparticles; Pomegranate seed oil; Pullulan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Candida albicans
  • Candidiasis* / drug therapy
  • Candidiasis, Vulvovaginal* / drug therapy
  • Candidiasis, Vulvovaginal* / microbiology
  • Clotrimazole / pharmacology
  • Clotrimazole / therapeutic use
  • Delivery, Obstetric
  • Female
  • Humans
  • Nanocapsules*
  • Pregnancy

Substances

  • Clotrimazole
  • Antifungal Agents
  • Nanocapsules