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Liposomes containing moxifloxacin: cytotoxicity, permeability in intestinal cells, electron microscopy and micronucleus

Grant number: 20/04793-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2020
Effective date (End): July 31, 2021
Field of knowledge:Health Sciences - Pharmacy
Principal researcher:Fernando Rogério Pavan
Grantee:Maria Carolina Franzini
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Since tuberculosis (TB) is still a global health issue and, several strategies to improve its treatment have been analyzed. Nanotechnology is one of them. Liposomes are nanostructures that were chosen for this project due to their capacity of encapsulating lipo or hydrophilic drugs and of using biocompatible lipids in their synthesis. Likewise, a moxifloxacin was the drug of choice to be nanocarried for being part of the new therapeutic guidelines for TB. In order to propose a new drug delivery approach using liposomes as nanobiotechnological systems for the administration of moxifloxacin against TB, this project aims to evaluate: the cytotoxicity of these liposomes with and without moxifloxacin against four mammalian cell lines, mutagenicity, their permeability in intestinal cells in vitro; the interaction between liposomes and macrophages using electron microscopy. The first stage of the project will be to assess cytotoxicity against macrophage strains (J774.A1), fibroblasts (MRC-5), hepatocytes (HepG2) and intestinal cells (Caco-2) by determining the cytotoxicity index (IC50). To do that, microdilution in 96-well plates and resazurin will be employed as a cell viability indicator. As a second step, the ability of the liposomes to induce DNA damage will be evaluated, so interphasic cells will be stained for analysis of the presence of micronuclei. The permeability of liposomes in monolayers of Caco-2 cells reports a possible relationship with oral bioavailability and will be evaluated by fluorescence confocal microscopy for qualitative purposes. As a last step, scanning electron microscopy will be performed to verify a supposed interaction between liposomes and macrophage cells, given the importance that this cell type has in the pathogenesis of the disease. As results, we expect that the combination of methods that seek a better understanding of the interaction between of different cell types and liposomes contribute to the analysis of the potential of this innovative drug delivery system developed in the treatment of TB.

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