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

Grant number: 19/11135-0
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): November 01, 2019
Effective date (End): October 28, 2020
Field of knowledge:Interdisciplinary Subjects
Principal researcher:Luiz Alberto Colnago
Grantee:William Marcondes Facchinatto
Supervisor abroad: Bruno Filipe Carmelino Cardoso Sarmento
Home Institution: Embrapa Instrumentação Agropecuária. Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA). Ministério da Agricultura, Pecuária e Abastecimento (Brasil). São Carlos , SP, Brazil
Research place: Universidade do Porto (UP), Portugal  
Associated to the scholarship:16/20970-2 - Study of chitosan and hydrophilic derivatives by time domain NMR, BP.DR

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.

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