Clotrimazole-loaded N-(2-hydroxy)-propyl-3-trimethylammonium, O-Palmitoyl chitosan micelles: preparation, characterization and in vitro evaluation against Candida species

Abstract

Vulvovaginal candidiasis is a fungal mucocutaneous infection responsible for 20-30% of vaginal infections, occurring mostly in women in reproductive age. Several approaches have been exploited to achieve higher drug stability by using vaginal-based formulations and devices instead of parenteral and oral administrations. Recently, polymer-based nanocarriers platforms have received increasing attention due to the adhesive interactions of nanoparticle/mucin interface and improvement on drug bioavailability. This mucoadhesiveness and the ability to cross cervicovaginal mucus barrier under adequate levels have been also associated with electrostatic attraction of negatively-charged mucin surface. In this sense, the biocompatible cationic polysaccharide chitosan, has been widely used as positively-charged surface of nanoparticles, being such property and the load capacity of lipophilic drugs improved in self-assembly structures of chitosan derivatives. Thus, this study aims to explore the chemical and biological advantages and potentialities of ammonium O-palmitoyl chitosan, DPCat, which has presented higher mucoadhesiveness and non-cytotoxicity to different cell lines, in order to improve the lipophilic antifungal clotrimazole activity against Candida spp. It will be performed the anti-Candida activity and toxicity of clotrimazole-loaded micelles to lower genital tract cells and will be used cell-monolayer models to induce permeability and cell accumulation of clotrimazole.