期刊
TISSUE ENGINEERING PART A
卷 23, 期 13-14, 页码 630-639出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2016.0524
关键词
hyaluronic acid; kartogenin; PEGylation; self-assembled micelles; osteoarthritis
资金
- National Research Foundation of Korea [2015R1A2A1A09002793]
- Korea Healthcare technology R&D project, Ministry for Health & Welfare Affairs, Republic of Korea [HI14C0322]
- National Research Foundation of Korea [2015R1A2A1A09002793] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Synthetic hyaluronic acid (HA) containing a covalently integrated drug is capable of releasing therapeutic molecules and is an attractive candidate for the intra-articular treatment of osteoarthritis (OA). Herein, self-assembled PEGylated kartogenin (PEG/KGN) micelles consisting of hydrophilic polyethylene glycol (PEG) and hydrophobic KGN, which has been shown to induce chondrogenesis in human mesenchymal stem cells, were prepared by covalent crosslinking. HA hydrogels containing PEG/KGN micelles (HA/PEG/KGN) were prepared by covalently bonding PEG chains to HA. The physicochemical properties of the HA/PEG/KGN conjugate gels were investigated using Fourier transform infrared spectroscopy, H-1 NMR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). HA/PEG/KGN gels exhibited larger micelles in aqueous solution than PEG/KGN. SEM images of PEG/KGN micelles showed a dark core and a bright shell, whereas PEG/KGN micelles covalently integrated into HA had an irregular oval shape. Covalent integration of PEG/KGN micelles in HA hydrogels significantly reduced drug release rates and provided sustained release over a prolonged period of time. HA/PEG/KGN hydrogels were degradable enzymatically by collagenase and hyaluronidase in vitro. Injection of HA/PEG/KGN hydrogels into articular cartilage significantly suppressed the progression of OA in rats compared with free-HA hydrogel injection. These results suggest that the HA/PEG/KGN hydrogels have greater potency than free-HA hydrogels against OA as biodegradable synthetic therapeutics.
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