Antifungal Properties of Nerolidol-Containing Liposomes in Association with Fluconazole

Camila Fonseca Bezerra; José Geraldo de Alencar Júnior; Rosilaine de Lima Honorato; Antonia Thassya Lucas Dos Santos; Josefa Carolaine Pereira da Silva; Taís Gusmão da Silva; Antonio Linkoln Alves Borges Leal; Thiago Sampaio de Freitas; Thiago Adler Tavares Vieira; Janaína Esmeraldo Rocha; Débora Lima Sales; José Maria Barbosa Filho; Gabriela Ribeiro de Sousa; Allyson Pontes Pinheiro; Jaime Ribeiro-Filho; Henrique Douglas Melo Coutinho; Maria Flaviana Bezerra Morais-Braga; Teresinha Gonçalves da Silva

doi:10.3390/membranes10090194

Antifungal Properties of Nerolidol-Containing Liposomes in Association with Fluconazole

Membranes (Basel). 2020 Aug 20;10(9):194. doi: 10.3390/membranes10090194.

Authors

Camila Fonseca Bezerra¹, José Geraldo de Alencar Júnior², Rosilaine de Lima Honorato³, Antonia Thassya Lucas Dos Santos³, Josefa Carolaine Pereira da Silva³, Taís Gusmão da Silva³, Antonio Linkoln Alves Borges Leal⁴, Thiago Sampaio de Freitas⁴, Thiago Adler Tavares Vieira⁴, Janaína Esmeraldo Rocha⁴, Débora Lima Sales⁴, José Maria Barbosa Filho⁵, Gabriela Ribeiro de Sousa⁵, Allyson Pontes Pinheiro³, Jaime Ribeiro-Filho⁶, Henrique Douglas Melo Coutinho⁴, Maria Flaviana Bezerra Morais-Braga³, Teresinha Gonçalves da Silva⁷

Affiliations

¹ Department of Pharmaceutical Sciences, Federal University of Pernambuco-UFPE, Recife-PE 50670-901, Brazil.
² Department of Pharmacy, Federal University of Ceará-UFC, Fortaleza-CE 60020-181, Brazil.
³ Department of Biological Sciences, Regional University of Cariri-URCA, Crato-CE 63105-010, Brazil.
⁴ Department of Biological Chemistry, Regional University of Cariri-URCA, Crato-CE 63105-010, Brazil.
⁵ Department of Pharmacy, Federal University of Paraíba-UFPB, João Pessoa-PB 58051-900, Brazil.
⁶ Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador-BA 40296-710, Brazil.
⁷ Departament of Antibiotics, Federal University of Pernambuco-UFPE, Recife-PE 50670-901, Brazil.

Abstract

(1) Background: Infections by Candida species represent a serious threat to the health of immunocompromised individuals. Evidence has indicated that nerolidol has significant antifungal properties. Nonetheless, its use is restricted due to a low water solubility and high photosensitivity. The incorporation into liposomes may represent an efficient alternative to improve the physicochemical and biopharmaceutical properties of this compound. The present study aimed to characterize the antifungal properties of liposomal nerolidol, alone or in combination with fluconazole. Of note, this is the first study reporting the antifungal activity of liposomal nerolidol and its potentiating effect in association with fluconazole. (2) Methods: The Inhibitory Concentration 50%-IC₅₀ and minimum fungicide concentrations (MFC) of the substances against Candida albicans (CA), Candida tropicalis (CT), and Candida krusei (CK) were established by subculture in a solid medium. To evaluate the antifungal-enhancing effect, the MFC of fluconazole was determined in the presence or absence of subinhibitory concentrations of nerolidol (free or liposomal). The analysis of fungal dimorphism was performed through optical microscopy and the characterization of liposomes was carried out considering the vesicular size, polydispersion index, and zeta medium potential, in addition to a scanning electron microscopy analysis. (3) Results: The physicochemical characterization revealed that liposomes were obtained as homogenous populations of spherical vesicles. The data obtained in the present study indicate that nerolidol acts as an antifungal agent against Candida albicans and Candida tropicalis, in addition to potentiating (only in the liposomal form) the effect of fluconazole. However, the compound had little inhibitory effect on fungal dimorphism. (4) Conclusions: The incorporation of nerolidol into liposomes improved its antifungal-modulating properties.

Keywords: antifungal resistance inhibition; candida dimorphism; fluconazole; liposomes; nerolidol.