| 李佳佳,孟祥莹,李 强,祝本菊,曹立梅,陈 旭.还原可降解聚磺酸甜菜碱型纳米水凝胶的制备及载药研究[J].,2019,19(18):3410-3416 |
| 还原可降解聚磺酸甜菜碱型纳米水凝胶的制备及载药研究 |
| Preparation and Drug Loading Characterization of Redox Biodegradable Nanogels Based on Sulfobetaine |
| 投稿时间：2019-05-09 修订日期：2019-06-03 |
| DOI：10.13241/j.cnki.pmb.2019.18.003 |
| 中文关键词: 还原可降解 聚磺酸甜菜碱甲基丙烯酸酯 纳米水凝胶 递药系统 |
| 英文关键词: Redox biodegradable PSBMA Nanogels Drug carrier |
| 基金项目:国家自然科学基金项目（81870920）；上海市徐汇区医学科研项目（SHXH201839） |
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| 中文摘要: |
| 摘要 目的：制备与表征还原可降解的聚磺酸甜菜碱型纳米水凝胶，利用该纳米递药系统包载阿霉素（DOX）并初步评价其抗肿瘤性能。方法：利用回流沉淀聚合的方法合成含二硫键的聚磺酸甜菜碱甲基丙烯酸酯（PSBMA）纳米水凝胶及不含二硫键的PSBMA纳米凝胶（nd-PSBMA）；通过粒度仪和透射电镜考察两种纳米水凝胶的粒径、形态以及稳定性； 通过考察谷胱甘肽（GSH）对纳米凝胶溶液相对浊度的影响以评价还原环境对两种纳米凝胶的还原可降解性；利用纳米凝胶包载阿霉素（DOX），考察载药凝胶在GSH中的释药行为，并初步评价其对A549肿瘤细胞的杀伤作用。结果：以N, N'-双丙烯酰胱胺为交联剂制备了含二硫键的PSBMA纳米凝胶，其粒径在180～200 nm；同时以N, N'-双丙烯酰胺为交联剂制备了不含二硫键的n-PSBMA纳米凝胶。两种纳米凝胶与小鼠血清共孵育7天水合粒径仍无明显变化，表明磺酸甜菜碱型纳米凝胶具有良好的抗蛋白吸附能力。此外，PSBMA纳米凝胶在GSH溶液中迅速地降解，且降解速度与GSH浓度呈正相关；而nd-PSBMA纳米凝胶在GSH溶液中几乎不降解。载DOX的PSBMA纳米凝胶可在GSH作用下快速的释放药物而载DOX的nd-PSBMA纳米凝胶在GSH作用下缓慢的释放药物；体外细胞实验显示空白纳米凝胶和载药nd-PSBMA对A549细胞无明显毒性作用，但载DOX的PSBMA纳米凝胶可高效地杀死A549肿瘤细胞，其药效与游离DOX相仿。结论：还原可降解的PSBMA纳米水凝胶有望成为智能型控释药物载体。 |
| 英文摘要: |
| ABSTRACT Objective: A redox biodegradable nanogels based on sulfobetaine were synthesized and characterized. DOX were encapsulated in the nanogels and the in vitro antitumor efficacy of the drug-loaded nanogels was also evaluated. Methods: Reflux precipitation polymerization was used to synthesis disulfide-containing poly (sulfobetaine methacrylate) (PSBMA) and nd-PSBMA without disulfide was also prepared as control. Dynamic scattering light (DLS) and transmission electron microscope (TEM) were used to evaluate the size and morphology of the nanogels. The reduction biodegradability of the nanogels was evaluated by the effects of glutathione (GSH) on the relative turbidity of nanogels. DOX was used as model drug to prepare drug-loaded nanogels. The drug release behavior and antitumor efficacy against A549 cells of DOX-loaded nanogels were also evaluated. Results: N,N'-bis(acryloyl) cystamine (BAC) was used as cross-linker to prepare PSBMA nanogels containing cleavable disulfide linkage; N,N'-methylenebisacrylamide (MBA) was used to synthesize nd-PSBMA without disulfide. The hydrophilic size of nanogels were 180~200 nm and remained invariable after incubation with mice serum for 7 days, reflecting excellent adsorption resistance capability. PSBMA nanogels degraded rapidly with GSH incubation. However, nd-PSBMA did not degrade with GSH. Consistently, DOX-loaded PSBMA nanogels released their encapsulated drugs fleetly with GSH and drug-loaded nd-PSBMA only slightly released drugs. MTT study showed that DOX-loaded PSBMA nanogels can cause similar cytotoxicity as compared with free DOX, while blank nanogels and DOX-loaded nd-PSBMA did not show significant cytotoxicity against A549 cells. Conclusion: Redox biodegradable PSBMA nanogels show great promise for smart stimulus-responsive drug carrier. |
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