Novel polymeric nanoparticles targeting the lipopolysaccharides of Pseudomonas aeruginosa

Int J Pharm. 2016 Apr 11;502(1-2):232-41. doi: 10.1016/j.ijpharm.2016.02.021. Epub 2016 Feb 17.

Abstract

Considering outburst of various infectious diseases globally, nanoparticle assisted targeted drug delivery has emerged as a promising strategy that can enhance the therapeutic efficacy and minimize the undesirable side effects of an antimicrobial agents. Molecular imprinting is a newly developed strategy that can synthesize a drug carrier with highly stable ligand-like 'cavity', may serve as a new platform of ligand-free targeted drug delivery systems. In this study, we use the amphiphilic lipopolysaccharides, derived from Pseudomonas aeruginosa as imprinting template and obtained an evenly distributed sub-40 nm polymeric nanoparticles by using inverse emulsion method. These molecularly imprinted nanoparticles (MIPNPs) showed specific binding to the lipopolysaccharide as determined by fluorescence polarization and microscale thermophoresis. MIPNPs showed selective recognition of target bacteria as detected by flow cytometry. Additionally, MIPNPs exhibited the in vivo targeting capabilities in both the keratitis model and meningitis model. Moreover, the photosensitizer methylene blue-loaded MIPNPs presented significantly strong inhibition of bacterial Growth, compared to non-imprinted controls for in vitro model of the photodynamic therapy. Our study shows an attempt to design a magic bullet by molecular imprinting that may provide a novel approach to generate synthetic carrier for targeting pathogen and treatment for a variety of infectious human diseases.

Keywords: Drug targeted delivery; Lipopolysaccharide; Molecular imprinting; Photodynamic therapy; Polymeric nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers / administration & dosage*
  • Drug Carriers / therapeutic use
  • Drug Delivery Systems*
  • Escherichia coli / drug effects
  • Keratitis / drug therapy
  • Light
  • Lipopolysaccharides* / metabolism
  • Meningitis / drug therapy
  • Methylene Blue / administration & dosage
  • Mice
  • Molecular Imprinting
  • Nanoparticles / administration & dosage*
  • Nanoparticles / therapeutic use
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage
  • Polymers / administration & dosage*
  • Polymers / therapeutic use
  • Pseudomonas Infections
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / metabolism
  • Rabbits

Substances

  • Drug Carriers
  • Lipopolysaccharides
  • Photosensitizing Agents
  • Polymers
  • Methylene Blue