甲氨蝶呤PLGA微球制备工艺及体外释药性能考察

Preparation and in vitro release of methotrexate PLGA microspheres

目的制备一种融合骨组织工程支架可用于骨肉瘤治疗的甲氨蝶呤(MTX)聚乳酸羟基乙酸共聚物(PLGA)的缓释降解微球,并考察其体外释药性能。方法采用O/W乳化剂挥发法制备MTX-PLGA载药微球。以聚乙烯醇(PVA)浓度,磁力搅拌器转速,温度为主要影响因素设计L 9(34)正交实验;以载药率,包封率及体外药物缓释百分比为试验指标,选择稳定且持续释放药物的最优微球加工工艺参数,利用释药动力学数学模型,考察微球体外释药机理。结果磁力搅拌器转速是影响微球质量的主要因素,在300 r·min^-1下,可制备出粒径较小包载甲氨蝶呤的PLGA微球,平均载药率为(3.3±0.16)%,包封率为(59.64±0.51)%。结论通过计算释药动力学数学模型,此方法下制备的微球体外释药是由扩散和溶蚀共同作用完成,满足生物可降解载药微球释药机理,为治疗骨肉瘤提供了新的可能。

Objective To prepare a kind of bone tissue engineering scaffolds which can be used for the treatment of Osteosarcoma,the sustained-release degradation microspheres of PLGA were prepared and their drug release properties in vitro were investigated.Methods MTX-PLGA microspheres were prepared by O/W emulsifier evaporation method.The L 9(34)orthogonal experiment was designed with polyvinyl alcohol concentration,Magnetic stirrer speed and temperature as the main influencing factors.The drug loading rate,entrapment rate and percentage of drug sustained release in vitro were used as test indexes,and the optimum processing parameters for preparing stable and sustained release microspheres were selected.Results The results showed that the average drug loading rate was(3.3±0.16)%,and the entrapment rate was(59.64±0.51)%,when the Magnetic stirrer speed was 300 r·min^-1,the PLGA microspheres with smaller particle size could be prepared.Conclusion Through the computational pharmacokinetic mathematical model,the in vitro drug release of the microspheres prepared by this method is completed by the joint action of diffusion and dissolution,which meets the drug release mechanism of biodegradable drug-loaded microspheres and provides a new possibility for the treatment of osteosarcoma.