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一种基于羧甲基己酰壳聚糖/透明质酸聚合物共混的新型可注射原位形成凝胶,用于延释小檗碱。

A novel injectable in situ forming gel based on carboxymethyl hexanoyl chitosan/hyaluronic acid polymer blending for sustained release of berberine.

机构信息

Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 11031, Taiwan, ROC; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, ROC.

Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan, ROC.

出版信息

Carbohydr Polym. 2019 Feb 15;206:664-673. doi: 10.1016/j.carbpol.2018.11.050. Epub 2018 Nov 19.

DOI:10.1016/j.carbpol.2018.11.050
PMID:30553371
Abstract

An in situ forming gel based on simply blending carboxymethyl hexanoyl chitosan (CHC) with low molecular weight hyaluronic acid (LMW HA) was developed, without needing cross-linking, photopolymerization or thermal treatments. The CHC/LMW HA blends formed nanoparticles and then rapidly transformed into supermolecular hydrogels under stirring. The gel formation mechanism was examined by Förster resonance energy transfer (FRET). The gels were injectable, cytocompatible and biodegradable, and showed shape-persistent behavior and adhesive property. Berberine, an anti-apoptotic and anti-arthritis naturally occurring compound, was encapsulated within the CHC/LMW HA gels. The gels demonstrated a pH-responsive characteristic which were able to release berberine in a sustained manner at pH 6.0 (simulating inflamed arthritic articular cartilage) and the degradation rates were accelerated at pH 7.4 (simulating healed normal tissue). The berberine-loaded gels effectively protected chondrocytes against sodium nitroprusside-induced apoptosis. The gels may be potentially useful as an injectable system for intra-articular drug delivery and cartilage tissue engineering.

摘要

一种基于简单混合羧甲基己酰壳聚糖 (CHC) 和低分子量透明质酸 (LMWHA) 的原位形成凝胶,无需交联、光聚合或热处理。CHC/LMWHA 混合物形成纳米颗粒,然后在搅拌下迅速转化为超分子水凝胶。通过荧光共振能量转移 (FRET) 研究了凝胶的形成机制。凝胶具有可注射性、细胞相容性和生物降解性,并表现出形状保持行为和粘附性。小檗碱是一种具有抗细胞凋亡和抗关节炎作用的天然化合物,被包裹在 CHC/LMWHA 凝胶中。凝胶表现出 pH 响应特性,能够在 pH 6.0(模拟发炎的关节炎关节软骨)下以持续的方式释放小檗碱,并且在 pH 7.4 下(模拟愈合的正常组织)降解速度加快。载有小檗碱的凝胶能有效保护软骨细胞免受亚硝基铁氰化钠诱导的细胞凋亡。该凝胶可作为关节内药物输送和软骨组织工程的潜在应用的注射系统。

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