基于硼酸邻苯二酚酯键的硼替佐米pH敏感型可控释放模型的研究  

A pH-Sensitive Controlled Release Model for Bortezomib based on the Catechol Borate Ester Bond

作　　者：杨伯涵[1] 赵外鸥 李采金 李亚鹏[1] 王静媛[1] 

机构地区：[1]吉林大学麦克德尔米德实验室化学学院,长春130012 [2]吉林大学第一医院,长春130012

出　　处：《高分子学报》2014年第5期636-642,共7页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号20904014);吉林省科技厅青年基金(基金号20080119);教育部青年基金(基金号2070310)资助项目

摘　　要：通过硼酸邻苯二酚酯键将抗癌药物硼替佐米（bortezomib，BTZ）连接到两亲型梳状聚衣康酸接枝共聚物（PIA—PEG—DDA—DPA）上，制备pH敏感型载药聚合物PIA—PEG．DDA—DPA—BTZ．通过核磁共振（NMR）表征了该聚合物的结构．DLS和AFM测试结果表明，该聚合物流体力学直径较小约为25～38nm；芘荧光法测定表明，其临界胶束浓度（CMC）为2．54×10^-3mg／mL．利用硼替佐米位于310nm处的紫外特征吸收峰，分别在模拟生理pH值（7．4）及溶酶体和内涵体pH值（5．0）的条件下，研究聚合物的释药行为，结果表明，该体系在生理pH环境下基本无释药行为，在溶酶体和内涵体pH环境下，BTZ的累计释放率随时间变化曲线符合一级动力学方程Q=61．65866—62．13481e-0.32544t．相关的细胞实验表明，该种载药聚合物体系对癌细胞的抑制作用明显，接近硼替佐米纯品的效果．A pH-responsive controlled release model for bortezomib （BTZ） based on catechol borate ester bond has been constructed successfully by poly（ ethylene glycol） （PEG） , dodecylamine （DDA） and dopamine （DPA）-modified poly itaconic acid （PIA） （PIA-PEG-DDA-DPA-BTZ）. Its structure was characterized by nuclear magnetic resonance （NMR）. The result showed that the targeted products were prepared successfully. The PIA-PEG-DDA-DPA-BTZ was then made into micelles. The sizes of the mieelles formed by the polymer were tested by dynamic light scattering （DLS）, and observed under atomic force microscope （AFM）. According to the test,the micelles showed a spherical and monodispersed construct with very small diameter of about 35 nm. The critical micelle concentration （CMC） value was 2.54 ×10^-3mg/mL via pyrene fluorescence method. The standard curve of BTZ was portrayed based on the characteristic absorption peak of BTZ at 300 nm in UV-Vis absorption. The cumulative release rates of BTZ conjugates were then studied at pH 5.0 and pH 7.4, and the release behavior at pH 5.0 fits the first order kinetics model, Q = 61. 65866 -62.13481 e-0.32544,, the coefficient of determination was 0. 99798. The cell viability studies showed that the mieelles had a quite significant inhibitory effect on cancer cells which is close to that of the pure bortezomib. The pH-responsive controlled release model has the potential of becoming a promising diagnostic tool in clinical application for cancer treatment.

关 键 词：硼替佐米 硼酸邻苯二酚酯键 PH敏感 释药方程 

分 类 号：TQ460.1[化学工程—制药化工]