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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 Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): November 01, 2019
Effective date (End): October 28, 2020
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Luiz Alberto Colnago
Grantee:William Marcondes Facchinatto
Supervisor: Bruno Filipe Carmelino Cardoso Sarmento
Host 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


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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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FACCHINATTO, WILLIAM MARCONDES; GALANTE, JOANA; MESQUITA, LETICIA; SILVA, DANIELLA SOUZA; DOS SANTOS, DANILO MARTINS; MORAES, TIAGO BUENO; CAMPANA-FILHO, SERGIO PAULO; COLNAGO, LUIZ ALBERTO; SARMENTO, BRUNO; DAS NEVES, JOSE. Clotrimazole-loaded N -(2-hydroxy)-propyl-3-trimethylammonium, O -palmitoyl chitosan nanoparticles for topical treatment of vulvovaginal candidiasis. Acta Biomaterialia, v. 125, p. 312-321, . (16/20970-2, 17/20973-4, 19/13656-8, 19/11135-0)

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