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- Title
Enzyme-Responsive Polymeric Vesicles for Bacterial-Strain-Selective Delivery of Antimicrobial Agents.
- Authors
Li, Yamin; Liu, Guhuan; Wang, Xiaorui; Hu, Jinming; Liu, Shiyong
- Abstract
Antimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain-selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase ( PGA) and β-lactamase ( Bla), which are closely associated with drug-resistant bacterial strains, antibiotic-loaded polymeric vesicles undergo self-immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain-selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β-lactam antibiotic drugs, as a further validation, we demonstrate methicillin-resistant S. aureus (MRSA)-triggered release of antibiotics from Bla-degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.
- Subjects
POLYMERIC composites; CHEMICAL synthesis; BLOCK copolymers; POLYMERIC drug delivery systems; DRUG resistance in bacteria; ANTIBIOTICS; REARRANGEMENTS (Chemistry)
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 5, p1792
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201509401