MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery

J. Guo, H. Sun, W. Lei, Y. Tang, S. Hong, H. Yang, Franklin Chi Meng Tay, C. Huang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Currently available drug delivery systems for oral diseases suffer from short retention time and poor local concentrations at the target site. A biodegradable stimulus-responsive hydrogel was synthesized in the present study to evaluate its application as an environmentally sensitive carrier for on-demand intraoral drug delivery. The hydrogel was synthesized from diacrylate-containing polyethylene glycol–based scaffolds and a cysteine-terminated peptide crosslinker (CGPQG↓IWGQC) via a Michael-type addition reaction. Because CGPQG↓IWGQC can be cleaved by matrix metalloproteinase 8 (MMP-8), minocycline hydrochloride, bovine serum albumin, or an antibacterial peptide (KSL) was incorporated into the scaffolds to evaluate the MMP-8-responsive release behavior of the on-demand drug delivery system. Hydrogel characterization and gelation kinetics were examined with gel time, Fourier-transform infrared spectroscopy, scanning electron microscopy, and measurements of rheologic parameters. Degradation behavior and MMP-8-responsive drug release were performed by high-performance liquid chromatography and protein-specific assay. Biocompatibility evaluation indicated that the hydrogels were noncytotoxic. Antibacterial testing demonstrated that the released drugs were able to maintain bioactivity. Taken together, these results suggest that the MMP-8-sensitive hydrogel is a promising candidate for on-demand intraoral localized drug delivery. Because MMP-8 is one of the most important biomarkers for periodontitis, the MMP-8-responsive hydrogel has potential to be used for in situ adaptive degradation in response to chronic periodontitis and peri-implantitis. This notion has to be tested in animal models of periodontal disease.

Original languageEnglish (US)
Pages (from-to)564-571
Number of pages8
JournalJournal of Dental Research
Volume98
Issue number5
DOIs
StatePublished - May 1 2019

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Keywords

  • controlled release
  • drug delivery systems
  • matrix metalloproteinases
  • peptides
  • peri-implantitis
  • periodontitis

ASJC Scopus subject areas

  • Dentistry(all)

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