对聚乳酸载药微球的形成过程进行了耗散颗粒动力学模拟和实验研究.载药体系以硝苯地平为模型药物、聚乳酸(poly-lactic acid, PLA)为载体材料、聚乙烯醇(poly vinyl alcohol, PVA)为稳定剂.通过研究,提出了聚乳酸载药微球的形成机理,认为微球形成过程可分为4个阶段,即高度分散阶段、PLA分子聚集阶段、硝苯地平分子向微球内部扩散阶段和微球的形成及稳定阶段.机理分析和模拟表明,微球对硝苯地平的包载量有一个临界值,硝苯地平浓度低于该值,几乎所有的硝苯地平分子都能扩散进微球的内部;高于该值,则部分硝苯地平分子难以扩散进微球内部,而分散在介质中,形成硝苯地平聚集体.
The dissipative particle dynamics (DPD) simulation method and experimental study were used to investigate the mechanism of poly-lactic acid (PLA) microspheres formation. Nifedipine was used as the model drug, PLA as the carrier, and poly vinyl alcohol (PVA) as the stabilizer, respectively. The mechanism of PLA microspheres formation was developed. The forming process of PLA microspheres consisted of four steps: (1) high dispersion, (2) aggregation of PLA molecules, (3) nifedipine molecules dispersion into the PLA matrix, (4) formation and stabilization of PLA microspheres, sequentially. Based on the mechanism analysis, it was pointed out that there was a maximum of the nifedipine content that the PLA matrix could carry. If the content of nifedipine was below the maximum, almost all the nifedipine molecules dispersed into the PLA matrix. However, when the nifedipine content exceeded the maximum, some nifedipine molecules would be repulsed outside the microspheres, resulting in surplus nifedipine molecules aggregation.