Scholarship 23/16304-0 - Ácido hialurônico, Ácidos graxos voláteis - BV FAPESP
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Development of mucoadhesive polymeric nanoparticles based on polysaccharides for co-encapsulation of mesalazine and propionate in the treatment of inflammatory bowel diseases

Grant number: 23/16304-0
Support Opportunities:Scholarships in Brazil - Master
Start date until: December 01, 2024
End date until: January 31, 2026
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Maria Palmira Daflon Gremião
Grantee:Ana Júlia Rocha Cardoso
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Inflammatory bowel diseases (IBD) cause chronic inflammation in the gastrointestinal system. The most prevalent IBDs are Crohn's disease (CD) and ulcerative colitis (UC), differing in the location of inflammation. As a first-choice treatment for IBD, mesalazine (MLZ) has been widely explored. MLZ inhibits the COX-1 and COX-2 enzymes, helping to reduce inflammation, but in the long term, it causes kidney problems. The development of colon-specific delivery systems, however, may favor the local selective pharmacological action of MLZ, improving its therapeutic efficacy and controlling the release rates, stability, and response time of the drug in colonic tissue. The use of polysaccharides, such as retrograded starch (RA) and hyaluronic acid (HA), in the formation of nanoparticles offers advantages such as biocompatibility, biodegradability, safety, and drug vectorization. AR presents an organized and compact three-dimensional network that resists digestion in the stomach and duodenum, being digested only in the colon. HA stands out due to its mucoadhesion properties, hydrophilicity, and ability to bind to CD44 receptors and because it is overexpressed in epithelial cells and macrophages in inflamed tissues. Furthermore, co-encapsulating two different compounds, such as MLZ together with propionate, in nanoparticles would enhance the therapy. Propionate, a postbiotic short-chain fatty acid (SCFA) generated by the fermentation of dietary fiber in the colon has anti-inflammatory properties. In view of the above, the present project aims to develop polymeric nanoparticles composed of HA and AR to co-encapsulate MLZ and propionate. The systems will be characterized and their performance will be evaluated through release studies, in vitro biological assays using 2D cellular models, and intestinal permeability.

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