Development of a dextrin-vitamin D3 micelle nanocarrier for the antimicrobial peptide LLKKK18 as a potential therapeutic agent for bone infections

J Mater Chem B. 2024 Nov 13;12(44):11464-11476. doi: 10.1039/d4tb00903g.

Abstract

In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against S. aureus, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Peptides / chemical synthesis
  • Antimicrobial Peptides / chemistry
  • Antimicrobial Peptides / pharmacology
  • Bone Diseases, Infectious / drug therapy
  • Cholecalciferol* / analogs & derivatives
  • Cholecalciferol* / chemistry
  • Cholecalciferol* / pharmacology
  • Dextrins* / chemistry
  • Dextrins* / pharmacology
  • Drug Carriers* / chemistry
  • Humans
  • Mice
  • Micelles*
  • Microbial Sensitivity Tests
  • Nanoparticles / chemistry
  • RAW 264.7 Cells
  • Staphylococcus aureus* / drug effects

Substances

  • Micelles
  • Cholecalciferol
  • Anti-Bacterial Agents
  • Dextrins
  • Drug Carriers
  • Antimicrobial Cationic Peptides
  • Antimicrobial Peptides
  • LLKKK18