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

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.
AuthorsVerônica Ferrari Cervi, Camila Parcianello Saccol, Ticiane da Rosa Pinheiro, Roberto Christ Vianna Santos, Marcel Henrique Marcondes Sari, Letícia Cruz
JournalDrug delivery and translational research (Drug Deliv Transl Res) Vol. 12 Issue 12 Pg. 2907-2919 (12 2022) ISSN: 2190-3948 [Electronic] United States
PMID35499713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2022. Controlled Release Society.
Chemical References
  • Clotrimazole
  • Antifungal Agents
  • Nanocapsules
Topics
  • Female
  • Humans
  • Pregnancy
  • Clotrimazole (pharmacology, therapeutic use)
  • Antifungal Agents (pharmacology, therapeutic use)
  • Candidiasis, Vulvovaginal (drug therapy, microbiology)
  • Candida albicans
  • Candidiasis (drug therapy)
  • Nanocapsules
  • Delivery, Obstetric

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