Abstract

Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as controlled local drug delivery systems. In this study, we prepared carboxymethyl chitin microspheres (CMCH-Ms) with a diameter of 10–100 μm through physical crosslinking by increasing temperature in an aqueous two-phase system without using organic solvents, surfactants and crosslinking agents. The stable microspheres keeping spherical shape with porous microstructure in different pH environments were embeded in thermosensitive hydroxypropyl chitin (HPCH) hydrogels. The morphology, gelation rate, swelling, rheological and mechanical properties, in vitro degradation and cytotoxicity, drug loading and drug release of the CMCH-Ms/HPCH gel scaffolds were examined. In vitro degradation and cytotoxicity test indicated that CMCH-Ms/HPCH gel scaffolds were biodegradable and non-cytotoxic. Moreover, no organic solvent was used in the preparation and drug loading process of CMCH-Ms/HPCH gel scaffold. Importantly, less burst drug release and long-term sustained-release from the CMCH-Ms/HPCH composite hydrogel was observed than those from only CMCH-Ms or HPCH hydrogel. Thus, the composite CMCH-Ms/HPCH hydrogel exhibited great potential application for loading different drugs and sustained drug release in controlled local drug delivery systems.

摘要

源自天然生物聚合物的微球和可注射水凝胶已作为受控局部药物递送系统进行了广泛研究。在本研究中，我们在不使用有机溶剂、表面活性剂和交联剂的情况下，通过在水性两相体系中升高温度，通过物理交联制备了直径为 10-100 μm 的羧甲基甲壳素微球（CMCH-Ms）。将在不同 pH 环境下保持球形并具有多孔微结构的稳定微球嵌入热敏羟丙基几丁质 (HPCH) 水凝胶中。检查了 CMCH-Ms/HPCH 凝胶支架的形态、凝胶速率、溶胀、流变学和机械性能、体外降解和细胞毒性、药物负载和药物释放。体外降解和细胞毒性试验表明CMCH-Ms/HPCH凝胶支架是可生物降解的，无细胞毒性。此外，CMCH-Ms/HPCH凝胶支架的制备和载药过程均未使用有机溶剂。重要的是，与仅使用 CMCH-Ms 或 HPCH 水凝胶相比，CMCH-Ms/HPCH 复合水凝胶的药物突释和长期持续释放更少。因此，复合 CMCH-Ms/HPCH 水凝胶在加载不同药物和在受控局部给药系统中持续释放药物方面表现出巨大的潜在应用。