超临界CO_(2)一步法制备载盐酸阿霉素和紫杉醇壳聚糖纳米粒  

One-step preparation of doxorubicin hydrochloride and paclitaxel co-loaded chitosan nanoparticles using supercritical carbon dioxide

作　　者：彭虎红 芮金州 关怡新[1] 姚善泾[1] PENG Hu-hong;RUI Jin-zhou;GUAN Yi-xin;YAO Shan-jing(College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China)

机构地区：[1]浙江大学化学工程与生物工程学院,浙江杭州310027

出　　处：《高校化学工程学报》2022年第1期76-84,共9页Journal of Chemical Engineering of Chinese Universities

基　　金：国家自然科学基金(21878262)。

摘　　要：双载药纳米给药系统能有效增强抗癌药物协同治疗效果、降低毒副作用。本研究以水-乙醇为共溶剂、利用强化混合超临界流体辅助雾化(SAA-HCM)技术一步法制备了同时负载盐酸阿霉素和紫杉醇的壳聚糖纳米粒,详细考察了水与乙醇的体积比、待处理液浓度、CO_(2)与溶液质量流量比、壳聚糖相对分子质量和沉淀器温度对纳米粒形貌及粒径分布的影响。在优化条件下制备得到的纳米粒球形度良好,平均粒径为(173±6.6)nm。固态表征结果表明,经SAA-HCM技术处理后药物结构保持完整、热稳定性不变、盐酸阿霉素和紫杉醇由晶体结构转变为无定形态。体外肿瘤细胞毒性实验表明,药物活性保持良好,同时负载盐酸阿霉素和紫杉醇的壳聚糖纳米粒具有癌细胞协同抑制效果。本研究拓展了SAA-HCM技术在双载药纳米给药系统中的应用,为其他协同给药纳米系统的绿色高效制备提供一定参考作用。Dual drug-loaded nanoparticles can enhance synergetic therapeutic efficiency and reduce side effects of anti-cancer drugs.Doxorubicin hydrochloride(DOX)and paclitaxel(PTX)co-loaded chitosan nanoparticles were successfully prepared by a modified supercritical fluid assisted atomization technique(SAA-HCM)from water/ethanol co-solvent system.Effects of water/ethanol volume ratio,solution concentration,CO_(2)/liquid mass flow ratio,chitosan molecular weight and drying temperature in the precipitator on morphology and nanoparticle size were investigated.Well defined spherical nanoparticles with average diameter of(173±6.6)nm were prepared under optimized operation conditions.The results of solid state characterization indicate the structure integrity of DOX and PTX after SAA-HCM processing and thermal behaviors of micronized DOX and PTX are consistent with raw materials.Meanwhile,changes of crystals to amorphous state of DOX and PTX were observed.The bioactivity of DOX and PTX was well maintained and obvious synergetic effects were observed after co-loaded in chitosan nanoparticles via in vitro cytotoxicity evaluation.This work expands the applicability of SAA-HCM technique to prepare dual drug-loaded nanoparticles and provides reference for efficient preparation of synergetic drug delivery systems using a green and sustainable technique.

关 键 词：超临界流体辅助雾化 双载药纳米粒 壳聚糖 盐酸阿霉素 紫杉醇 

分 类 号：TQ469[化学工程—制药化工]