Wang Yang, Zheng Jin, Tian Yefei, Yang Wuli
State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
J Mater Chem B. 2015 Jul 28;3(28):5824-5832. doi: 10.1039/c5tb00703h. Epub 2015 Jun 22.
To improve the biocompatibility and biodegradability of nanocarriers, well-defined poly(vinylcaprolactam)-based acid degradable nanogels were fabricated for drug delivery via precipitation polymerization in water, where synthetic ketal-based 2,2-dimethacroyloxy-1-ethoxypropane (DMAEP) acted as a cross-linker, and N-(2-hydroxypropyl)methacrylamide (HPMA) served as a co-monomer. Expectedly, we observed that the temperature and pH of the environment play important roles in the performance of the nanogels. The nanogels were reduced in size upon increasing the temperature and showed higher volume phase transition temperature (VPTT) with higher concentration of HPMA. With the incorporation of ketal linkages, the nanogels showed accelerated degradation profiles by lowering the pH and increasing temperature of the incubation medium. When used as nanocarriers of anticancer drug doxorubicin (DOX), compared to non-degradable nanogels with similar components, the acid-degradable nanogels displayed more effective drug controlled release behaviour, low drug leakage of DOX at neutral pH while rapid and sufficient release from the nanogels under acidic conditions. The results of the cytotoxicity and hemolysis assays further highlighted that the acid-degradable nanogel produced no hemolysin but showed excellent viability to normal cells, and the DOX-loaded nanogel exhibited higher proliferation inhibition against tumor cells.
为了提高纳米载体的生物相容性和生物降解性，通过在水中沉淀聚合制备了结构明确的基于聚（乙烯基己内酰胺）的酸可降解纳米凝胶用于药物递送，其中基于缩酮的2,2 - 二甲基丙烯酰氧基 - 1 - 乙氧基丙烷（DMAEP）作为交联剂，N - （2 - 羟丙基）甲基丙烯酰胺（HPMA）作为共聚单体。不出所料，我们观察到环境的温度和pH值在纳米凝胶的性能中起着重要作用。随着温度升高，纳米凝胶尺寸减小，并且在HPMA浓度较高时表现出更高的体积相变温度（VPTT）。通过引入缩酮键，纳米凝胶通过降低孵育介质的pH值和升高温度显示出加速的降解曲线。当用作抗癌药物阿霉素（DOX）的纳米载体时，与具有相似成分的不可降解纳米凝胶相比，酸可降解纳米凝胶表现出更有效的药物控释行为，在中性pH下DOX的药物泄漏低，而在酸性条件下从纳米凝胶中快速且充分释放。细胞毒性和溶血试验结果进一步表明，酸可降解纳米凝胶不产生溶血素，但对正常细胞具有优异的活力，并且负载DOX的纳米凝胶对肿瘤细胞表现出更高的增殖抑制作用。
