Evaluation of the potential of liposomes for co-encapsulation of amphotericin B and micafungin in the treatment of systemic infection caused by Candida auris

Abstract

The Candida auris species has been prominent in the medical field in recent years due to its involvement in cases of systemic infections, mainly in the nosocomial environment. Authorities around the world remain alert to the rapid progression of pathological conditions attributed to this species due to the scarcity of available drug approaches for treatment. Thus, new research for therapeutic alternatives has been explored in recent years, mainly in the area of Pharmaceutical Nanotechnology. Liposomes are classified as an important drug delivery system aiming primarily at optimizing the pharmacological properties of bioactive principles as well as reducing levels of toxicity. The versatility of this system attracts research in several areas of science, especially microbiology, since antimicrobial drugs with therapeutic restrictions are optimized for use in therapies of severe infections. The aim of this work is to evaluate the potential of liposomes for the co-encapsulation of amphotericin B (AMB) and micafungin (MICA), two important drugs widely used in candidemia therapy, aiming at the treatment of systemic infections triggered by C. auris. The liposomes will be synthesized from cholesterol, soybean phosphatidylcholine and PBS buffer by hydration techniques of the lipid film for the encapsulation of MICA and AMB. Physical-chemical characterization tests (transmission electron microscopy, determination of mean particle diameter, zeta potential, polydispersity index, in vitro release assays and encapsulation efficiency) will be performed. Biological analyzes to evaluate inhibitory potential in vitro against C. auris (determination of activity against planktonic cells, fungicidal inhibition kinetics, inhibition of mature and forming biofilms, ergosterol-sorbitol interaction assays, combination assays and resistance development) will be performed with MICA and AMB free and co-encapsulated in liposomes, as well as toxicity experiments (in vitro cytotoxicity on cell lines and in vivo alternative model of acute toxicity in Gallerea melonella) and experimental in vivo assay (in vivo experimental trial of C. auris candidemia therapy) will be developed. In summary, this work will seek to reach new perspectives in the treatment of systemic infections caused by C. auris, presenting a new therapeutic approach for available drugs.