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Getting the Jump on the Development of Bullfrog Oil Microemulsions: a Nanocarrier for Amphotericin B Intended for Antifungal Treatment

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Abstract

Amphotericin B (AmB), a potent antifungal drug, presents physicochemical characteristics that impair the development of suitable dosage forms. In order to overcome the AmB insolubility, several lipid carriers such as microemulsions have been developed. In this context, the bullfrog oil stands out as an eligible oily phase component, since its cholesterol composition may favor the AmB incorporation. Thus, the aim of this study was to develop a microemulsion based on bullfrog oil containing AmB. Moreover, its thermal stability, antifungal activity, and cytotoxicity in vitro were evaluated. The microemulsion formulation was produced using the pseudo-ternary phase diagram (PTPD) approach and the AmB was incorporated based on the pH variation technique. The antifungal activity was evaluated by determination of minimal inhibitory concentration (MIC) against different species of Candida spp. and Trichosporon asahii. The bullfrog oil microemulsion, stabilized with 16.8% of a surfactant blend, presented an average droplet size of 26.50 ± 0.14 nm and a polydispersity index of 0.167 ± 0.006. This system was able to entrap AmB up to 2 mg mL−1. The use of bullfrog oil as oily phase allowed an improvement of the thermal stability of the system. The MIC assay results revealed a growth inhibition for different strains of Candida spp. and were able to enhance the activity of AmB against T. asahii. The microemulsion was also able to reduce the AmB toxicity. Finally, the developed microemulsion showed to be a suitable system to incorporate AmB, improving the system’s thermal stability, increasing the antifungal activity, and reducing the toxicity of this drug.

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Acknowledgments

The authors wish to thank CAPES and PIBIC/CNPQ for the financial support and Asmarana Produtos Naturais for providing fatty tissue from bullfrogs.

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Author notes

  1. Wógenes N. Oliveira and Lucas Amaral-Machado contributed equally to this work.

Authors and Affiliations

  1. Graduate Program in Pharmaceutical Sciences, Dispersed Systems Laboratory (LaSid), Federal University of Rio Grande do Norte (UFRN), Rua General Gustavo Cordeiro de Faria, S/N, Natal, RN, 59012-570, Brazil

    Wógenes N. Oliveira, Guilherme M. Chaves & Eryvaldo Socrates T. Egito

  2. Graduate Program in Health Sciences, LaSiD, UFRN, Natal, RN, Brazil

    Lucas Amaral-Machado, Everton N. Alencar, Henrique R. Marcelino, Julieta Genre, Walicyranison P. Silva-Rocha, Guilherme M. Chaves & Eryvaldo Socrates T. Egito

  3. Chemistry Department, UFRN, Natal, RN, Brazil

    Amanda D. Gondim

  4. Laboratory of Pharmaceutical Technology & Biotechnology (TecBioFar), Department of Pharmacy, UFRN, Natal, RN, Brazil

    Matheus F. Fernandes-Pedrosa

  5. National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil

    Eryvaldo Socrates T. Egito

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  1. Wógenes N. Oliveira
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  2. Lucas Amaral-Machado
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Contributions

Wógenes N. de Oliveira, Lucas Amaral-Machado, and Éverton N. Alencar performed the experiments. Wógenes N. de Oliveira, Lucas Amaral-Machado, and Éverton N. Alencar performed the literature search and drafted the manuscript. Wógenes N. de Oliveira, Lucas Amaral-Machado, and Walicyranison P. Silva-Rocha were responsible for the antifungal activity assay. Wógenes N. Oliveira, Lucas Amaral-Machado, Julieta Genre, Henrique R. Marcelino, Guilherme M. Chaves, Amanda D. Gondim, Matheus F. Fernandes-Pedrosa, and Eryvaldo S. T. Egito contributed to the development of the concept, data analysis, and writing of the manuscript.

Corresponding author

Correspondence to Eryvaldo Socrates T. Egito.

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Oliveira, W.N., Amaral-Machado, L., Alencar, E.N. et al. Getting the Jump on the Development of Bullfrog Oil Microemulsions: a Nanocarrier for Amphotericin B Intended for Antifungal Treatment. AAPS PharmSciTech 19, 2585–2597 (2018). https://doi.org/10.1208/s12249-018-1093-1

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