Evaluation of the against resistant Mycobacterium tuberculosis activity of N-acetylcysteine-chitosan nanoparticles conjugated with the antimicrobial peptide Ctx(Ile21)-Ha-Ahx-Cys loaded with rifampicin.

• Grant number: 22/09728-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2022
• Effective date (End): October 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Laura Maria Duran Gleriani Primo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis, the leading cause of death from infection in the world, is caused by the bacillus Mycobacterium tuberculosis (MTB). The research for new drugs is prioritized, especially after the latest report of many rifampicin resistant strains, and the pandemic of SARS CoV-2. Many strategies that use nanotechnology have been explored to improve the activity of obsolete drugs, particularly when they are conjugated with other biomacromolecules. N-acetylcysteine-chitosan (NAC-Q) is a modified polysaccharide that has characteristics similar to chitosan- such as degradation, low toxicity, and antimicrobial activity- but with more stable physicochemical properties, better mucoadhesion, and controlled release. Previously we reported a potential antimicrobial activity of NAC-Q (as ultrathin films) when it is conjugated with the antimicrobial peptide Ctx(Ile21)-Ha derived from a brazilian Cerrado frog's skin secretion. This conjugated compound had a significant value of inhibition of Pseudomonas aeruginosa e Staphylococcus aeurus. With that demonstrated, this project intends to develop a nanoparticles based on NAC-Q conjugated with the Ctx(Ile21)-Ha-Ahx-Cys and load it with rifampicin, to evaluate the anti-MTB action against the standard strain H37Rv and extremely resistant CF169. These results could facilitate the understanding and importance of the use of nanobioconjugated macromolecules for the treatment of MTB.

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)

POLINARIO, GIULIA; PRIMO, LAURA MARIA DURAN GLERIANI; ROSA, MAIARA ALANE BARALDI CERQUETANI; DETT, FREDDY HUMBERTO MARIN; BARBUGLI, PAULA ABOUD; ROQUE-BORDA, CESAR AUGUSTO; PAVAN, FERNANDO ROGERIO. Antimicrobial peptides as drugs with double response against Mycobacterium tuberculosis coinfections in lung cancer. FRONTIERS IN MICROBIOLOGY, v. 14, p. 17-pg., 2023-06-02. (22/09728-6, 20/16573-3, 20/13497-4, 21/14603-5)