多重响应的介孔碳载药体系的制备与初步评价  

Preparation and evaluation of multiple-stimuli responsive mesoporous carbon based drug delivery system

作　　者：张琳 严新 洪贺远 丛熙岩 巴鑫 赵勤富[1] ZHANG Lin;YAN Xin;HONG Heyuan;CONG Xiyan;BA Xin;ZHAO Qinfu(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2022年第1期1-9,共9页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81603058);辽宁省大学生创新创业训练计划项目(201910163011)。

摘　　要：目的为了能更好的使药物作用于肿瘤部位,同时减少药物对其他部位的毒副作用,研究制备了近红外(near infrared,NIR)、pH和还原多重响应型的介孔碳(mesoporous carbon nanoparticles,MCN)药物递送系统。方法研究将聚丙烯酸(polyacrylic acid,PAA)通过二硫键接枝于MCN表面,构建出还原/pH/NIR多重响应性递送系统(MCN-SS-PAA)。采用透射电镜、比表面积及孔径分布仪、近红外热成像仪和Zeta电位测定仪等进行表征。选取抗癌药阿霉素(doxorubicin,DOX)作为模型药物,考察药物的还原、pH和NIR多重敏感性释放。结果体外升温结果显示体系具有浓度依赖性和功率依赖性。在pH 7.4磷酸盐缓冲液(phosphate buffer solution,PBS)中,药物释放量较低,在pH 5.0 PBS中药物释放量增加,而在10 mmol·L^(-1)谷胱甘肽(glutathione,GSH)存在的条件下,药物的释放量进一步增加。当在808 nm激光器照射下,药物释放呈现阶梯式增长。表现出明显的还原、pH和NIR多重响应型释药特征。当PAA修饰在载体表面,体系的溶血百分率和蛋白吸附量明显降低。结论研究构建的载药系统具有明显还原、pH和NIR多重响应型释药特征和近红外的升温效果,为化疗-热疗的联合应用提供了新的思路。Objective To increase the therapeutic effect in the tumor sites and reduce the toxic and side effects of the drugs towards to normal cells,the near infrared(NIR),pH and reduction multiple-responsive mesoporous carbon nanoparticles(MCN)delivery system was developed.Methods The polyacrylic acid(PAA)was grafted on the surface of MCN via disulfide bonds to construct a reduction/pH/NIR multiple-responsive delivery system(MCN-SS-PAA).In this study,the transmission electron microscopy(TEM),specific surface area and pore size analyzer,IR-thermal imager and Zeta potential analyzer were used to characterize the prepared MCN-SS-PAA.And the doxorubicin(DOX)was used as a model drug to evaluate the reduction/pH/NIR multiple-responsive drug release.Results The in vitro photothermal effect showed that the MCN-SS-PAA system was concentration dependent and power dependent.In pH 7.4 phosphate buffer solution(PBS),the drug release was lower,while in pH 5.0 PBS,the drug release was increased.In presence of 10 mmol·L^(-1)GSH,the release of DOX was further increased.When irradiated by 808 nm laser,the drug release showed a step-by-step accelerated release,thus showing obvious characteristics of reduction,pH and NIR multiple-responsive drug release.When PAA was modified on the surface of the carrier,the percentage of hemolysis and the amount of protein adsorption markedly decreased.Conclusion The constructed drug delivery system DOX/MCN-SS-PAA has the characteristics of reduction/pH/NIR multiple-responsive drug release and the good thermal heating effect under NIR irradiation,which provides a new idea for the combined application of chemotherapy and hyperthermia.

关 键 词：介孔碳 阿霉素 多重响应敏感 聚丙烯酸 

分 类 号：R94[医药卫生—药剂学]