Glucose-sensitive delivery of metronidazole by using a photo-crosslinked chitosan hydrogel film to inhibit Porphyromonas gingivalis proliferation

Int J Biol Macromol. 2019 Feb 1:122:19-28. doi: 10.1016/j.ijbiomac.2018.09.202. Epub 2018 Oct 1.

Abstract

A novel glucose-sensitive drug delivery system with controlled release of metronidazole was synthesized by using biocompatible photo-crosslinked chitosan hydrogel film. Specifically, methacrylic anhydride, as photosensitive substance, was firstly grafted on chitosan molecular chains and then UV irradiation was applied as the crosslinking method. Glucose sensitivity was endowed by immobilizing glucose oxidase on the surface of chitosan film. The physicochemical characteristics including chemical composition, crosslinking degree, mechanical strength and related enzyme properties were investigated successively. Cytotoxicity test, drug release and anti-bacterial test were carried out, respectively. The results show that this photo-crosslinked hydrogel film has good mechanical properties; meanwhile, the immobilized enzyme's bonding capacity and activity can maintain a relatively high level after surface activation. In addition, this material possesses better biocompatibility than chemical crosslinked samples. What's more, it can sense the ambient glucose stimulus, rapidly and correspondingly adjust its inner pore structure to control the loaded metronidazole release, lead to an improved antimicrobial activity against Porphyromonas gingivalis under high glucose concentration. This glucose sensitive hydrogel film may provide a promising method for diabetic's periodontitis therapy in clinic.

Keywords: Anti-microbial; Chitosan; Controlled release metronidazole; Glucose-sensitive; Photo-crosslinking.

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Cell Proliferation / drug effects
  • Chitosan / chemistry*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Enzymes, Immobilized / chemistry
  • Enzymes, Immobilized / metabolism
  • Glucose / metabolism*
  • Glucose Oxidase / chemistry
  • Glucose Oxidase / metabolism
  • Materials Testing
  • Methylgalactosides / chemistry*
  • Metronidazole / chemistry*
  • Metronidazole / pharmacology*
  • Mice
  • Microbial Sensitivity Tests
  • Photochemical Processes*
  • Porphyromonas gingivalis / cytology
  • Porphyromonas gingivalis / drug effects*

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Enzymes, Immobilized
  • Methylgalactosides
  • hydrogel film
  • Metronidazole
  • Chitosan
  • Glucose Oxidase
  • Glucose