多二硫键聚醚氨酯核壳载药微粒的制备及性能研究

Preparation of Stimuli Responsive Nanoparticles Using Coaxial Electrospray Template Removal Method and Its Application as Drug Delivery System

利用"同轴电喷-去模板技术"制备了载药效率接近100%,且具有核-壳结构和氧化还原响应性的药物控释微球.首先通过同轴电喷技术,制备了以聚乙二醇(PEG)为壳,主链含多个二硫键的聚醚氨酯(PEU)为核的微球.通过"去模板"方法,脱去PEG层,可以使所制备的微球的尺寸从微米减小到纳米尺度.在含二硫苏糖醇(DTT)的媒介中,PEU可以快速降解.体外释药的结果显示,在含谷胱甘肽(GSH)的媒介中,载药纳米微球可在12 h内将其所包载的药物的80%释放出,具有显著的氧化还原响应性控制释放药物的特征.

Redox-responsive microparticles with core-shell structure were prepared by the coaxial electrospray technique. Poly（ether methane） （PEU） with multiple-disulfide bonds in the main chain was synthesized via a facile one-pot method. It was found that the number average molecular weight of the resultant polymer decreased from 3.1 × 10^7 to 6.6 × 10^6 in 8 h in the presence of DL-dithiothreitol （DTT）. The microparticles with PEU as the core and polyethylene glycol （PEG） as the shell were prepared by the coaxial electrospray technique. The results of the microscopies （the scanning electron microscopy and laser scanning confocal microscopy） showed that the constructed microparticles were spherical, uniform and with a distinct core-shell structure. It was also found that the mean diameter of the prepared microparticles decreased to less than 100 nm when the PEG shell was removed. Dynamic light scattering results showed that the hydrodynamic mean diameter of the particles after PEG template removal was about 112 nm. The spherical nanoparticles could be completely decomposed when they were placed in phosphate buffer saline （PBS） solution at pH = 7.4 ＋ 10 mmol/L L-glutathione （GSH） for 24 h at 37 -C. In contrast, the shape of the spherical nanoparticles remained unchanged in PBS without GSH after 24 h. The doxorubicin （DOX） loaded nanoparticles were also prepared with the coaxial electrospray technique, and the results showed that the drug-loading efficiency was nearly 100%. Meanwhile, under the condition of GSH, the content of the cumulative drug release could be up to 80% within 12 h at 37 -C, in contrast to the case that only 50% of the loaded DOX could release within 12 h in the absence of GSH. This study shows that the prepared nano drug delivery system has the characteristics of significant GHS response and controlled drug release.