复合壳聚糖纳米微球聚乳酸-羟基乙酸/纳米羟基磷灰石缓释载体系统对蛋白的缓释作用

Delayed release of compound chitosan nano-microspheres PLGA/nHA control-releasing carrier systems

背景：聚乳酸-羟基乙酸支架材料具有良好的生物相容性、无毒、可以良好的塑性,并具有一定的强度和韧性。但其降解产物为酸性,会影响局部pH值变化,不利组织生长。目的：制备能够良好缓释蛋白类药物的复合支架。方法：以牛血清蛋白为模型药物,以离子凝胶法制备壳聚糖微球。将微球与纳米羟基磷灰石和聚乳酸-羟基乙酸按一定比例混合,以冰粒子为致孔剂,采用粒子沥虑-冷冻干燥复合工艺制备CMs/nHA/PLGA复合缓释支架。利用扫描电镜、透射电镜、压泵仪和力学性能测试仪检测复合支架的形态和性能,并考察其在体外对蛋白类药物释放的规律。结果与结论：制备的壳聚糖纳米微球形态良好,呈规则球形或类球形,粒径分布在220～770nm,以380～650nm为多。微球对药物的载药量为39.2%,包封率为68.3%,两者均与牛血清蛋白的初始量相关,载药量随牛血清蛋白初始量的增加而增加,包封率则反之。复合支架呈白色多孔状,孔径为125～355mm,孔与孔之间联通良好,孔隙率达83.4%,压缩强度为1.4~2.1MPa,10周降解率为28.6%。PLGA/nHA支架对牛血清蛋白的2d累积释放量为85%,而壳聚糖和CMs/nHA/PLGA复合支架对牛血清蛋白的9d累积释放量分别是为48.9%和35.7%。提示制作的壳聚糖纳米微球和CMs/nHA/PLGA支架材料对牛血清蛋白有良好的缓释作用,复合支架材料形态好,强度和降解速率合适。

BACKGROUND：Polylactic acid-glycolic acid（PLGA） is a kind of biodegradable polymer with excellent biocompatibility,plasticity and certain strength and toughness.But its degradation products are acidic,which can affect local pH and inhibit tissue growth.OBJECTIVE：To prepare composite scaffolds with excellent characteristics of delayed release of proteins.METHODS：Using bovine serum album（BSA） as model protein,chitosan microspheres（CMs） were prepared by ionotropic gelation.Ice particulates were used as porogen.Composite scaffolds were prepared with CMs/nHA/PLGA by freeze-drying.Scanning electron microscope,transmission electron microscope,mercury porosimeter and universal testing machine ware used to observe the characteristic and morphology of the composite scaffolds.RESULTS AND CONCLUSION：The CMs were spherical in shape with a regular surface.The diameters of the CMs were in the range of 220-770 nm,mainly ranging 380-650 nm.The encapsulation efficiency of the CMs was 68.3%,and the loading capacity was 39.2%.The both were related with the initial concentration of BSA.The pore diameter of the composite scaffolds was about 125-355 m,the porosity was 83.4%,and the compressive strength was about 1.4-2.1 MPa.The cumulative degradation was 28.6% at 10 weeks.The cumulative release of BSA from PLGA/nHA scaffolds was 85% in 2 days,which from CMs and CMs/nHA/PLGA scaffolds was 48.9% and 35.7% in 9 days.The CMs microspheres and CMs/nHA/PLGA scaffolds have a desirable release rates for BSA and strength,are expected to use as carrier for growth factor and bone tissue engineering scaffolds.