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Effects of lipidic nucleus nanocapsule containing Annexin A1 in Ulcerative Colitis model induced in mice

Grant number: 18/26383-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2019
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Sandra Helena Poliselli Farsky
Grantee:Milena Fronza Broering
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Annexin A1 (AnxA1) is a 37 KDa protein secreted by several cells with inflammatory response modulating role. AnxA1, an important anti-inflammatory protein, modulates experimental colitis and our research group has shown that AnxA1 mediates the treatment of the disease with infliximab. Lipid core nanocapsules (LNCs) carry molecules of different natures, including biological products, and have the ability to cross endogenous barriers, demonstrating therapeutic efficacy after oral administration. Thus, the present project aims to encapsulate AnxA1 in LNC (LNC-AnxA1) and to test its efficacy in the in vivo model of experimental colitis induced by DSS in C57Bl/6 mice by oral administration, in addition to elucidating the effects of the same in cells Caco-2, a gastrointestinal epithelial line. The encapsulation of AnxA1 and its physico-chemical characterization will be carried out in the nanotechnology laboratory of the Federal University of Rio Grande do Sul, following the protocol established by Professors Silvia Guterres and Adriana Polhmann. Recombinant AnxA1 (rAnxA1) will be provided by Dr. Chris Reutlelinsgperger of the University of Maastrich, The Netherlands. Experimental colitis will be induced by oral administration of 3% DSS already established in our laboratory. Treatment with LNC-AnxA1 will be performed from the 6th day until the 10th day after the onset of colitis induction orally at a concentration of 25 ¼g per day. On day 11, colon and blood samples will be collected for histological characterization, immunohistochemistry, cell characterization of the lamina propria by flow cytometry, cell signaling pathways, leukogram and plasma cytokines, as well as calculating the activity index of the disease. In vitro studies with stimulated Caco-2 cells and observing the secretion of inflammatory mediators such as TNF-± permeability and integrity of the cell barrier, as well as changes in the molecules of the intercellular junctions important for the development of the disease. Together, the results obtained may contribute to the application of rAnxA1 as a therapeutic tool for colitis, a chronic disease that does not have effective treatment that affects more and more people worldwide. (AU)