Polyelectrolytic Chitosan Complexes with Dextran Sulfate and Carboxymetildextran containing methotrexate potentially applicable as mucus-modulating systems in Chron's disease

• Grant number: 20/04396-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2020
• End date: July 31, 2021
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Palmira Daflon Gremião
• Grantee: Jamily Angela Sant Anna Carvalho
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Chron's disease (CD) is a type of inflammatory bowel disease (IBD) characterized by transmural inflammation, which affects the entire thickness of the organ. The mucosa, submucosa and muscular layer of discontinuous parts of the GIT are affected by the inflammatory process and the presence of ulcerations. Recent studies point to mucosal healing as the guiding paradigm for CD therapy. Here, mucus, the main barrier that covers the GIT's mucosa has been shown to be an important target in investigations. Mucus is altered in DC and one of the current hypotheses in the area is that the restructuring of its barrier properties can act synergistically to the mucosal healing process. The evolution of knowledge about mucoadhesive delivery systems in our research group in recent years has shown that integrated mucoadhesion / mucopenetration strategies can be more advantageous in diseases in which multiple biological responses are necessary when compared only to mucoadhesion strategies. This integration is achieved through mucus- modulating systems capable of modulating the properties of mucus. In this project, it is proposed to develop potentially mucus-modulating particles by combining materials that have different interaction profiles with mucus: the polycation chitosan (CS) with different anionic biopolymers, Dextran-Sulfate (DS) or Carboxymethyl-Dextran (CMD) . The systems will be used as carriers of methotrexate (MTX), an immunosuppressive drug used in the treatment of CD. We hope to obtain micrometric and submicrometric polyelectrolyte complexes with distinct and functional properties to act in the CD treatment.