左旋甲基多巴分子印迹纳米给药系统的合成、表征及药物缓释研究

采用沉淀聚合法合成了左旋甲基多巴(L-Methyldopa, LMD)分子印迹聚合物微球(MIPMs), 并对其合成条件进行了详细研究. 结果表明, 聚合温度和引发剂的用量对微球的大小和形态有较大的影响, 微球的粒径随聚合温度的降低而增大, 随偶氮二异丁睛(AIBN)量的增大而增大. 而模板分子似乎对微球粒径的影响不是很明显. 通过扫描电镜、静态吸附试验(BET)和斯卡查德分析(Scatchard analysis)、红外光谱分析和模拟人体胃液扩散实验等对微球的外貌形态、吸附性能、分子印迹效果和药物缓释效果进行了表征. BET吸附实验和Scatchard 分析结果表明, 分子印迹聚合微球(MIPMs)的最大静态吸附量是非印迹聚合物微球(NIPMs)的3倍. 药物扩散实验表明, LMD在非印迹微球(NIPMs)上的释药率几乎与时间呈直线关系, 说明其释药过程完全受扩散控制; 而LMD在MIPMs上的释药率则呈曲线上升趋势, 说明其释药过程除了受扩散控制外, 还受到药物模板分子与MIPMs之间的印迹效应的协同作用的控制, 从而达到了缓释药物分子的目的. 实验结果表明, 在模拟胃液中, MIPMs释放药物的持续时间(10 h)是NIPMs持续时间(5 h)的2倍, 表明分子印迹微微球确实具有缓释药物的效果. 因此, MIPMs有望进一步应用于LMD药物缓释系统的研究.

Synthesis and Characterization of Molecularly Imprinted Polymeric Microspheres for L-Methyldopa and Its Application to Drug Delivery System

The molecularly imprinted polymeric microspheres (MIPMs) for L-methyldopa (LMD) were synthesized by precipitation polymerization. The influences of synthetic conditions such as polymerization temperature, the amount of initiator (AIBN) and the property of template on the morphologies and diameter sizes of MIPMs were investigated in details. The results indicated that the morphologies of MIPMs were evi-dently affected by the polymerization temperature and the amount of AIBN. The diameters of MIPMs were decreased with increasing the polymerization temperature but increased with increasing the amount of AIBN, while the influences of template on the diameters of microspheres are not visible. The resultant MIPMs was characterized by scanning electronic microscopy (SEM), IR analysis, BET adsorption test and Scatchard analysis as well as the controlled release test in mimetic gastric juice (pH= 1). The IR analyses proved that the polymerization effects really occurred. The BET adsorption test indicated that the adsorption amount of MIPMs to LMD was as three times as that of non-imprinted microspheres (NIPMs). The con-trolled release test indicated that the release ratio of LMD on NIPMs was linearly increased with increasing time, which suggests that the release process is completely controlled by diffusion. Meanwhile, the release ratio of LMD on MIPMs was curvedly increased with increasing time, which indicates that the release proc-ess is controlled by both diffusion and the imprinting effect. And the release time was prolonged. The results indicate that the MIPMs released the LMD for 10 h while the NIPMs for only 5 h in the mimetic gastric juice. Therefore, the resultant MIPMs of LMD looks forward to being used as the materials for DDS.