近红外和pH双重响应的介孔碳药物递送系统的制备与初步评价

Preparation and preliminary evaluation of near-infrared and pH dual-responsive mesoporous carbon carrier drug delivery system

目的为了提高药物疗效,降低毒副作用,研究制备了近红外(near-infrared,NIR)和pH双重响应型的介孔碳(mesoporous carbon,MCN)递送系统。方法首先以十六烷基三甲基氯化铵(cetyltrimethyl ammonium chloride,CTAC)为模板,正硅酸乙酯(ethyl orthosilicate,TEOS)为硅源,酚醛树脂为碳源制备介孔碳载体,然后用浓硫酸和过硫酸铵对载体进行羧基化修饰,最后将聚乙二醇(polyethylene glycol,PEG)修饰在MCN表面,增加载体的分散性和生物相容性。研究采用透射电镜、比表面积及孔径分布仪、Zeta电位测定等对载药体系进行表征。此外,阿霉素(adriamycin,DOX)作为模型药物,并对体系的NIR和pH响应性释放行为进行考察。结果体外升温效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(PBS)中,药物释放量较低,而在pH 5.0 PBS中药物释放量增加。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pH和NIR双重响应型释药特征。当PEG修饰在载体表面,体系的溶血百分率明显降低。结论研究构建的载药系统具有明显pH和NIR双重响应型药物释药特征,为化疗-热疗的联合应用提供了新的思路。

Objective To improve the efficacy of the drug and reduce the side effects,a near-infrared(NIR)and pH dual-responsive mesoporous carbon(MCN)delivery system was developed.Methods First,using cetyltrimethylammonium chloride(CTAC)as a template,tetraethyl orthosilicate(TEOS)as the silicon source,phenolic resin as the carbon source to prepare mesoporous carbon carrier,then concentrated sulfuric acid and persulfate ammonium were used to carboxylate the carrier.And finally polyethylene glycol(PEG)was modified on the surface of MCN to increase the dispersibility and biocompatibility of the carrier.The drug-loading system was characterized by transmission electron microscopy,specific surface area and pore size distribution analyzer,and Zeta potential measurement.In addition,doxorubicin(DOX)was used as a model drug and the NIR and pH dual-responsive release behavior of the system was examined.Results The in vitro photothermal effect showed that MCN-PEG had the concentration-dependent and power-dependent ability.In pH 7.4 phosphate buffered saline(PBS),the amount of drug released was relatively low,while the amount of drug released was increased in pH 5.0 PBS.After being irradiated with an 808-nm laser,drug release showed a stepwise increase,exhibiting the pH and NIR dual-responsive release characteristics.After PEG was modified on the surface of the carrier,the percentage of hemolysis of the system was significantly reduced.Conclusion The drug-loading system constructed by the study has obvious pH and NIR dual-responsive drug release characteristics,which provides a new idea for the combined application of chemotherapy and hyperthermia.