纳米丝素颗粒药物缓释剂的研制及在治疗小鼠溃疡性结肠炎中的药物控制释放作用

利用天然丝素良好的生物相容性和生物可降解性,制备纳米丝素颗粒作为药物缓释载体。通过磷酸盐缓冲液及乙醇综合处理1 mg/mL丝素蛋白溶液得到颗粒直径比较均匀的纳米级丝素颗粒。电子显微镜下观察到丝素蛋白在pH 8.0的磷酸盐缓冲液作用下其链状胶束结构发生聚集而将药物包裹,自组装形成规则的直径为200～600 nm的球形颗粒,完成与药物的结合,即药物的搭载。在pH 8.0的缓冲液中,单纯柳氮磺吡啶(SASP)药物粉末在1 h左右即将药量的90%释放出来,而加入纳米丝素蛋白的丝素载体药物2 h释放出约60%的药物量,使达到最高药物浓度的时间比单纯药物粉末延长,从而延长药物作用时间,有利于机体对药物的有效吸收利用。将丝素载体药物用于治疗人工诱导小鼠慢性溃疡性结肠炎,结果丝素载体药物治疗组小鼠6～12 h血液药物浓度和结肠组织中的药物浓度降低幅度要低于单纯SASP药物治疗组小鼠,证实了纳米丝素蛋白具有良好的载药、释药功能。

Preparation of Nano Silk Fibroin Particles and Its Application as Drug Controlled-release Carrier Against Mouse Ulcerative Colitis

Natural silk fibroin is a promising material for preparing nano silk fibroin particles as drug controlled-release carrier due to its good biocompatibility and biodegradability.Nano silk fibroin particles of even size were obtained by treating 1 mg/mL silk fibroin solution with phosphate buffer and ethanol.Electron microscopic observation revealed that,under the action of pH 8.0 buffer,the micellar chain-like structure of silk fibroin gathered together,packaged the drug,and auto-assembled into spherical particles with diameters of 200 ～ 600 nm,thus completing association with the drug,i.e.,carrying the drug.In pH 8.0 phosphate buffer,the single salazosulfapyridine(SASP) drug powder released 90% of its dosage at about 1 h,while the nano silk fibroin carried drug released about 60% of its dosage at 2 h.Compared to single drug powder,drug carrier delayed the time to reach the peak drug concentration,thus extending effective time of the drug and being helpful for the body to absorb and utilize the drug effectively.We used the silk fibroin carried drug to treat the mice with induced chronic ulcerative colitis.The result showed that the reductions of drug concentration at 6 to 12 h in the treatment group with carried drug were lower than those with single SASP drug,confirming that nano silk fibroin has good drug-carrying and drug-delivering properties.