可塑形抗感染纳米羟基磷灰石药粒的研制及体外释放的实验研究

A plastic anti-infective nano-HA drug delivery implant

目的研制可塑形抗感染纳米羟基磷灰石(nano-HA)缓释药粒,为骨髓炎的治疗提供一种新型的局部药物缓释系统(LDDS)。方法采用nano-HA为载药核心载体,外包裹生物相容性好且可降解的聚羟基丁酸酯-羟基戊酸酯共聚物/聚乙二醇(PHBV/PEG),承载硫酸庆大霉素(GM)制成nano-HA-PHBV/PEG-GM缓释微球,复合nano-HA-PHBV/PEG-GM缓释微球与纤维蛋白凝胶(FS)研制出一种可塑形LDDS,研究其抑菌作用及体外释药特性。结果可塑形LDDS药粒有明显的抑菌圈,对金黄色葡萄球菌的抑菌作用长达56d,体外释放实验显示第1天释放量为154.3μg/mL,其后下降并以较低水平稳定释放,维持有效释药时间在49d以上。结论可塑形抗感染nano-HA药粒具有良好的体外缓释作用,操作简便,可预塑成各种形状的特点,为治疗骨髓炎提供了一条有效的治疗途径。

Objective To test the releasing property of a self-developed plastic drug delivery implant of anti-infective nano-hydroxyapatite （nano-HA） so as to provide a new local drug delivery system （LDDS） for treatment of osteomyelitis. Methods The nano-HA was used as the core carrier to load gentamicin （GM） . It was coated with poly hydroxybutyrate-co-hydroxyvalerate / polyethylene glycol （PHBV/PEG） to prepare the nano-HA-PHBV/ PEG-GM microspheres which were mixed with the fibrin sealant （FS） to develop a plastic implant. Then its antibacterial and in vitro releasing properties were investigated. Results The plastic LDDS implant was found to have a fine drug delivery capability. The bacterial growth inhibition zone was found around the LDDS for 56 days in the antibacterial test. Three samples were soaked with liquid of PBS （phosphate buffered saline）. The titer of GM released within the first day was 154. 3 μg/mL, and then the releasing maintained a slow level in the following days. After 49 days＇ releasing, the titer was 6.9 μg/mL which was still higher than the MIC （2 μg/mL） （minimaI inhibitory concentration） of GM. Conclusion The plastic LDDS has a fine in vitro releasing property and may have a widespread application in treatment of osteomyelitis.