Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections

J Control Release. 2024 May:369:39-52. doi: 10.1016/j.jconrel.2024.03.021. Epub 2024 Mar 22.

Abstract

The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.

Keywords: Antibacterial; Antibiofilm; Charge-switchable; Fluorinated micelles; pH responsive.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Betaine* / administration & dosage
  • Betaine* / analogs & derivatives
  • Betaine* / chemistry
  • Biofilms* / drug effects
  • Ciprofloxacin* / administration & dosage
  • Ciprofloxacin* / chemistry
  • Ciprofloxacin* / pharmacology
  • Drug Liberation
  • Fluorocarbons / chemistry
  • Fluorocarbons / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Lipase* / metabolism
  • Methicillin-Resistant Staphylococcus aureus* / drug effects
  • Micelles
  • Polymers / chemistry
  • Polymethacrylic Acids / chemistry
  • Staphylococcal Infections* / drug therapy

Substances

  • Anti-Bacterial Agents
  • Lipase
  • Betaine
  • Ciprofloxacin
  • Fluorocarbons
  • Micelles
  • Polymers
  • Polymethacrylic Acids