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

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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.

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Acknowledgements

We gratefully acknowledge UFSM and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-BR) and CNPq. We also would like to thank C.B. Silva for zetasizer access and Charlene Menezes for Zetasizer and Mastersizer analysis. We would also like to thank Atlas Assessoria Linguística for language editing.

Funding

Verônica Ferrari Cervi was granted a Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-BR) master’s fellowship (process number: 88882.427737/2019–01). Letícia Cruz for received PQ fellowship from CNPq (process number: 315612/2020–7).

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Authors and Affiliations

  1. Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Verônica Ferrari Cervi, Camila Parcianello Saccol, Ticiane da Rosa Pinheiro, Roberto Christ Vianna Santos, Marcel Henrique Marcondes Sari & Letícia Cruz

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  1. Verônica Ferrari Cervi
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  2. Camila Parcianello Saccol
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Contributions

All authors substantially contributed to developing this study by discussing, interpreting, reviewing, and commenting on the results. All authors approved the final version of this manuscript. Additionally, each author provided specific contributions: Verônica Ferrari Cervi: methodology, data curation, formal analysis, investigation, writing—original draft, writing—review & editing, visualization, conceptualization; Camila Parcianello Saccol: methodology, data curation, investigation, writing—review & editing; Ticiane da Rosa Pinheiro: methodology, data curation, conceptualization, writing—review & editing; Roberto Christ Viana Santos: methodology, conceptualization; writing—review & editing; Marcel Henrique Marcondes Sari: methodology, data curation, investigation, visualization, conceptualization, writing—review & editing; Letícia Cruz: conceptualization, methodology, writing—original draft, writing—review & editing, supervision, funding acquisition.

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Correspondence to Letícia Cruz.

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Cervi, V.F., Saccol, C.P., da Rosa Pinheiro, T. et al. A novel nanotechnological mucoadhesive and fast-dissolving film for vaginal delivery of clotrimazole: design, characterization, and in vitro antifungal action. Drug Deliv. and Transl. Res. 12, 2907–2919 (2022). https://doi.org/10.1007/s13346-022-01154-1

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