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通过酸不稳定邻酯键将 pH 敏感的羧甲基壳聚糖水凝胶用作可植入药物递送系统。

pH-sensitive carboxymethyl chitosan hydrogels via acid-labile ortho ester linkage as an implantable drug delivery system.

机构信息

Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Science, Anhui University, 111 Jiu long Road, Hefei, Anhui Province, 230601, PR China.

Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Science, Anhui University, 111 Jiu long Road, Hefei, Anhui Province, 230601, PR China.

出版信息

Carbohydr Polym. 2019 Dec 1;225:115237. doi: 10.1016/j.carbpol.2019.115237. Epub 2019 Aug 23.

DOI:10.1016/j.carbpol.2019.115237
PMID:31521291
Abstract

A series of pH-sensitive carboxymethyl chitosan (CMCS) hydrogels were prepared via ortho ester linkage. DOX-loaded gelatin nanoparticles with an average diameter of around 50 nm were incorporated into hydrogels to obtain hybrid hydrogels (DOX-NPs-Gel), which could be locally implanted into tumor site in any shape. The physicochemical and mechanical properties of these hydrogels could be easily controlled by adjusting the proportion of crosslinking agent. DOX-NPs-Gel showed the pH-dependent degradation and drug release, and only 29.9% of DOX was released within 144 h at pH 7.4, while the cumulative release reached 49.3% and 65% at pH 6.5 and 5.0, respectively. In vivo study demonstrated that the implanted DOX-NPs-Gel efficiently improved DOX accumulation in tumor site through continuously degradation in mildly acidic environment of tumor tissues, and the tumor volume at the end of experiment was only 81.53 mm, while tumor size reached to 229.22 mm and 174.15 mm after intravenous treatment with free DOX and DOX-NPs, respectively.

摘要

通过正交酯键合成了一系列 pH 敏感的羧甲基壳聚糖(CMCS)水凝胶。将平均直径约为 50nm 的载多柔比星明胶纳米粒(DOX-NPs)掺入水凝胶中得到杂化水凝胶(DOX-NPs-Gel),可将其以任意形状局部植入肿瘤部位。通过调整交联剂的比例可以轻松控制这些水凝胶的物理化学和机械性能。DOX-NPs-Gel 表现出 pH 依赖性降解和药物释放,在 pH 7.4 下 144 小时内仅释放了 29.9%的 DOX,而在 pH 6.5 和 5.0 下分别释放了 49.3%和 65%的 DOX。体内研究表明,植入的 DOX-NPs-Gel 通过在肿瘤组织的轻度酸性环境中持续降解,有效地提高了肿瘤部位的 DOX 积累,实验结束时肿瘤体积仅为 81.53mm3,而静脉注射游离 DOX 和 DOX-NPs 后肿瘤大小分别达到 229.22mm3和 174.15mm3。

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