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

药物输送 聚乙二醇 自愈水凝胶 生物相容性 化学 牙周炎 控制释放 生物医学工程 材料科学 药品 药理学 牙科 生物化学 纳米技术 高分子化学 医学 有机化学
作者
Jingyi Guo,Hanxiao Sun,Lei Wang,Yufeng Tang,Sihui Hong,Hongye Yang,Franklin R. Tay,Cui Huang
出处
期刊:Journal of Dental Research [SAGE]
卷期号:98 (5): 564-571 被引量:45
标识
DOI:10.1177/0022034519831931
摘要

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.
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