Amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid for the treatment of vulvovaginal candidiasis

Carolina Mirtes Melo; Jéssica Ferreira Cardoso; Fernanda Barçante Perassoli; Ari Soares de Oliveira Neto; Luccas Moreira Pinto; Maria Betânia de Freitas Marques; Wagner da Nova Mussel; Juliana Teixeira Magalhães; Sandra Aparecida de Lima Moura; Marcelo Gonzaga de Freitas Araújo; Gisele Rodrigues Da Silva

doi:10.1016/j.carbpol.2019.115608

Amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid for the treatment of vulvovaginal candidiasis

Carbohydr Polym. 2020 Feb 15:230:115608. doi: 10.1016/j.carbpol.2019.115608. Epub 2019 Nov 11.

Affiliations

¹ School of Pharmacy, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil. Electronic address: carol_mirtes@hotmail.com.
² School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: jee.ferreirac@gmail.com.
³ School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: fernandaperasoli@yahoo.com.br.
⁴ School of Pharmacy, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil. Electronic address: arisoaresneto@gmail.com.
⁵ School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: moreiraluccas@gmail.com.
⁶ Chemistry Department, Federal Univesity of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: betanialf@hotmail.com.
⁷ Chemistry Department, Federal Univesity of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: wdmussel@yahoo.com.br.
⁸ School of Pharmacy, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil. Electronic address: julimagaufsj@gmail.com.
⁹ Department of Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: sandralmoura@gmail.com.
¹⁰ School of Pharmacy, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil. Electronic address: mgfaraujo@ufsj.edu.br.
¹¹ School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: giselersilva@ufop.edu.br.

PMID: 31887870
DOI: 10.1016/j.carbpol.2019.115608

Abstract

The treatment of vulvovaginal candidiasis (VVC) is based on oral and vaginal formulations which show limited effectiveness. In this study, amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) were developed to overcome the drawbacks of the conventional formulations. AMP EUD nanoparticles/HA were synthesized by nanoprecipitation, formulated by statistical experimental design, and characterized. AMP release from EUD nanoparticles/HA and its antifungal activity in a murine model of VVC were evaluated. Nanoparticles showed 147.6 ± 16.7 nm of diameter, 0.301 ± 0.09 of polydispersity index, - 29.9 ± 3.76 mV of zeta potential, and 87.27 % of encapsulation efficiency. They released about 81 % of AMP in 96 h; and provided the elimination of 100 % of the vaginal fungal burden in 24 h. It was suggested that the AMP EUD nanoparticles/HA penetrated into the vaginal epithelium via CD44 receptors. These AMP EUD nanoparticles/HA represent a non-conventional vaginal formulation to improve the treatment of VVC.

Keywords: Amphotericin B; Amphotericin B-loaded Eudragit RL100 nanoparticles coated with Hyaluronic Acid; Chloramphenicol; Chloroform; Copolymer of poly(ethylacrylate, methyl-methacrylate, and chloro trimethyl-ammonioethyl methacrylate); Cyclophosphamide; Dibasic sodium phosphate dodecahydrate; Estradiol cypionate; Eudragit RL100; Hyaluronic acid; Hyaluronic acid sodium salt; Methanol; Phosphoric acid; Polyoxyethylenesorbitan monooleate; Potassium phosphate monobasic; Sodium hydroxide; Vulvovaginal Candidiasis.