AB2-type amphiphilic block copolymer containing a pH-cleavable hydrazone linkage for targeted antibiotic delivery

Int J Pharm. 2020 Feb 15:575:118948. doi: 10.1016/j.ijpharm.2019.118948. Epub 2019 Dec 16.

Abstract

A novel AB2-type amphiphilic block copolymer [OA-CN-NH-(PEG)2] with hydrazone linkage was synthesized and explored for pH-triggered antibiotic delivery. Vancomycin (VCM) loaded micelles of the polymer [OA-CN-NH-(PEG)2-VCM] were spherical in shape with size, polydispersity index, zeta potential and entrapment efficiency of 130.33 ± 7.36 nm, 0.163 ± 0.009, -4.33 ± 0.55 mV and 39.61 ± 4.01% respectively. The dilution stability study exhibited no significant change in the size distribution of OA-CN-NH-(PEG)2-VCM micelles up to 320-fold dilution. An in vitro drug release assay confirmed greater release of VCM from OA-CN-NH-(PEG)2-VCM at pH 6, compared to pH 7.4. An in vitro antibacterial activity evaluation of OA-CN-NH-(PEG)2-VCM showed 2-fold enhancement in antibacterial activity of VCM after 54 h of incubation against Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) at acidic pH compared to physiological pH. An in vivo antibacterial activity of OA-CN-NH-(PEG)2-VCM further proved the enhanced activity of OA-CN-NH-(PEG)2-VCM against MRSA. In conclusion, micelles from pH-responsive OA-CN-NH-(PEG)2 could be utilized for site-specific delivery of VCM at the infection site.

Keywords: Amphiphilic polymer; Hydrazone linkage; MRSA; Site-specific delivery; Vancomycin; pH cleavable.

MeSH terms

  • A549 Cells
  • Anti-Bacterial Agents
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Drug Stability
  • Hep G2 Cells
  • Humans
  • Hydrazones / chemistry*
  • Hydrogen-Ion Concentration
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Micelles
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Surface Properties
  • Technology, Pharmaceutical / methods
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Hydrazones
  • Micelles
  • Polyethylene Glycols
  • Vancomycin