Article, 2024

Antimicrobial peptides grafted onto the surface of N-acetylcysteine-chitosan nanoparticles can revitalize drugs against clinical isolates of Mycobacterium tuberculosis

Carbohydrate Polymers, ISSN 0144-8617, Volume 323, 10.1016/j.carbpol.2023.121449

Contributors

Primo L.M.D.G. [1] Roque-Borda C.A. 0000-0002-9262-0383 (Corresponding author) [1] [2] Carnero Canales C.S. [3] Caruso I.P. [1] de Lourenco I.O. [1] Colturato V.M.M. [4] Sabio R.M. [1] de Melo F.A. [1] Vicente E.F. [1] Chorilli M. [1] da Silva Barud H. [4] Barbugli P.A. [1] Franzyk H. 0000-0003-3004-5958 [2] Hansen P.R. 0000-0001-9357-8001 [2] Pavan F.R. 0000-0002-6969-3963 [1]

Affiliations

  1. [1] Universidade Estadual Paulista
  2. [NORA names: Brazil; America, South];
  3. [2] University of Copenhagen
  4. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  5. [3] Department of Physics and Formal Sciences and Engineering
  6. [NORA names: Peru; America, South];
  7. [4] Medical School
  8. [NORA names: Brazil; America, South]

Abstract

Tuberculosis is caused by Mycobacterium tuberculosis (MTB) and is the leading cause of death from infectious diseases in the World. The search for new antituberculosis drugs is a high priority, since several drug-resistant TB-strains have emerged. Many nanotechnology strategies are being explored to repurpose or revive drugs. An interesting approach is to graft antimicrobial peptides (AMPs) to antibiotic-loaded nanoparticles. The objective of the present work was to determine the anti-MTB activity of rifampicin-loaded N-acetylcysteine-chitosan-based nanoparticles (NPs), conjugated with the AMP Ctx(Ile)-Ha; against clinical isolates (multi- and extensively-drug resistant) and the HRv strain. The modified chitosan and drug-loaded NPs were characterized with respect to their physicochemical stability and their antimycobacterial profile, which showed potent inhibition (MIC values <0.977 μg/mL) by the latter. Furthermore, their accumulation within macrophages and cytotoxicity were determined. To understand the possible mechanisms of action, an in silico study of the peptide against MTB membrane receptors was performed. The results presented herein demonstrate that antibiotic-loaded NPs grafted with an AMP can be a powerful tool for revitalizing drugs against multidrug-resistant M. tuberculosis strains, by launching multiple attacks against MTB. This approach could potentially serve as a novel treatment strategy for various long-term diseases requiring extended treatment periods.

Keywords

Antimicrobial peptide, Extensively drug-resistant, Mycobacterium tuberculosis, N-acetylcysteine-chitosan

Funders

  • Fundação de Amparo à Pesquisa do Estado de São Paulo
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção
  • National Technology-Science Institute for Polysaccharides
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Polysaccharides

Data Provider: Elsevier