TY - JOUR
T1 - MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery
AU - Guo, J.
AU - Sun, H.
AU - Lei, W.
AU - Tang, Y.
AU - Hong, S.
AU - Yang, H.
AU - Tay, Franklin Chi Meng
AU - Huang, C.
N1 - Funding Information:
The authors thank Professor Xianzheng Zhang, Department of Chemistry, Wuhan University, for providing facilities and materials. This work was financially supported by the National Nature Science Foundation of China (No. 81771112), Hubei Natural Science Foundation (No. 2015CFA072), and the Fundamental Research Funds for the Central Universities (No. 2015304020201). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Funding Information:
The authors thank Professor Xianzheng Zhang, Department of Chemistry, Wuhan University, for providing facilities and materials.
Publisher Copyright:
© International & American Associations for Dental Research 2019.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - controlled release
KW - drug delivery systems
KW - matrix metalloproteinases
KW - peptides
KW - peri-implantitis
KW - periodontitis
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U2 - 10.1177/0022034519831931
DO - 10.1177/0022034519831931
M3 - Article
C2 - 30876379
AN - SCOPUS:85063035994
SN - 0022-0345
VL - 98
SP - 564
EP - 571
JO - Journal of Dental Research
JF - Journal of Dental Research
IS - 5
ER -