DEAE-chitosan nanoparticles as a pneumococcus-biomimetic material for the development of antipneumococcal therapeutics

Carbohydr Polym. 2021 Dec 1:273:118605. doi: 10.1016/j.carbpol.2021.118605. Epub 2021 Aug 25.

Abstract

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.

Keywords: Chitosan; Diethylaminoethyl; Enzybiotics; Nanoparticles; Pneumococcus.

MeSH terms

  • A549 Cells
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / metabolism
  • Chitosan / analogs & derivatives*
  • Chitosan / chemistry
  • Chitosan / metabolism
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Liberation
  • Endopeptidases / chemistry
  • Endopeptidases / pharmacology*
  • Humans
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Streptococcus pneumoniae / drug effects

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Drug Carriers
  • diethylethylamine-chitosan
  • Chitosan
  • Endopeptidases
  • endolysin