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Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes

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Abstract

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

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(Adapted from Oliveira et al. [35])

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Data Availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank Silvia Stanisçuaski Guterres for the access to the equipment for nanoparticle characterization. We acknowledge Evonik for the Eudragit® RS100 donation.

Funding

This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (project number 423066/2018–8) and Universidade Federal do Rio Grande do Sul (project number 35887).

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Authors and Affiliations

  1. Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Azenha, Porto Alegre, RS, 90610-000, Brazil

    Francielli Lima dos Santos, Andressa Urbano Machado, Irene Clemes Kulkamp Guerreiro, Alexandre Meneghello Fuentefria & Renata Vidor Contri

  2. Programa de Pós-Graduação em Ciências Farmacêuticas - PPGCF, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil

    Júlia Capp Zilles, Morgana Souza Marques, Bárbara Souza da Costa, Irene Clemes Kulkamp Guerreiro, Alexandre Meneghello Fuentefria & Renata Vidor Contri

  3. Programa de Pós-Graduação em Farmacologia e Terapêutica - PPGFT, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90050-170, Brazil

    Irene Clemes Kulkamp Guerreiro & Alexandre Meneghello Fuentefria

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  1. Francielli Lima dos Santos
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Contributions

Conceptualization: F.L.S., A.U.M., M.S.M., A.M.F., I.C.K.G., and R.V.C.; investigation: F.L.S., J.C.Z., and B.S.C.; data curation: F.L.S, J.C.Z., and R.V.C.; writing—original draft preparation: F.L.S., A.U.M., J.C.Z., and R.V.C.; writing—review and editing: F.L.S., J.C.Z., M.S.M., B.S.F., A.M.F., I.C.K.G., and R.V.C.; supervision: A.M.F., I.C.K.G., and R.V.C.; project administration: R.V.C.; resources and funding acquisition: A.M.F., I.C.K.G., and R.V.C. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Renata Vidor Contri.

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dos Santos, F.L., Zilles, J.C., Machado, A.U. et al. Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes. AAPS PharmSciTech 24, 198 (2023). https://doi.org/10.1208/s12249-023-02657-x

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