壳聚糖修饰的载胰岛素聚乳酸-羟基乙酸共聚物纳米粒的生物黏附性及毒性评价  

Evaluation of Bioadhesion and Toxicity of Chitosan-Coated Insulin-Loaded poly(lactide-co-glycolide) Nanoparticles

作　　者：郑爱萍[1] 曹德英[2] 毕芸祺[1] 崔旭[2] 张晓燕[1] 孙建绪[1] 

机构地区：[1]军事医学科学院毒物药物研究所药剂研究室,北京100850 [2]河北医科大学药学院,石家庄056002

出　　处：《中国药学杂志》2010年第13期1005-1010,共6页Chinese Pharmaceutical Journal

摘　　要：目的探讨壳聚糖修饰的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒的生物黏附性,阐明其促吸收机制,并考察纳米粒的细胞毒性以评价其安全性。方法以胰岛素为模型药物,采用FITC标记胰岛素,复乳法制备普通PLGA纳米粒,壳聚糖包裹制备生物黏附性PLGA纳米粒。粒度及表面电位分析仪测量纳米粒的粒径及Zeta电位,超速离心法测定载药纳米粒的包封率,通过测定胃肠道中胰岛素的总量评价纳米粒的生物黏附性,并采用MTT法评价PLGA纳米粒的细胞毒作用。结果纳米粒粒径均一,PLGA普通纳米粒及生物黏附性纳米粒的平均粒径分别为(124.7±11)和(136.6±13)nm,粒径差别不大,但壳聚糖包衣显著地增强了纳米粒的正电性,使得Zeta电位由负值(-1.67±0.05)mV逆转为正值(42.6±0.3)mV,并且提高了药物的包封率,由(46.67±1.82)%增至(52.73±2.96)%。生物黏附性纳米粒口服后胃肠道中胰岛素的总量显著高于普通纳米粒,3h达到1.31倍。MTT法显示生物黏附性PLGA纳米粒及普通PLGA纳米粒在所考察的剂量范围内(≤25mg.mL-1),均对细胞无特殊毒性。结论壳聚糖修饰的PLGA生物黏附性纳米粒是蛋白多肽类药物口服给药的良好载体。OBJECTIVE To elucidate its mechanism of enhancing absorption of chitosan coated poly（lactide-co-glycolide）（PLGA） bioadhesive nanoparticles （CS-PLGA-NP）,and to evaluate the bioadhesive and cytotoxity of PLGA nanoparticles （PLGA-NP）.METHODS Insulin was chosen as model drug and it was labeled by Fluorescein-isothiocyanate （FITC-insulin）. Insulin-loaded PLGA nanoparticles were achieved by double-emulsion methods,which were coated by chitosan in order to obtain bioadhesive nanoparticles. Nanoparticle size and Zeta potentials were measured by zetasizer nano analyser. The entrappment efficiency of insulin-loaded nanoparticles was surveyed by supercentrifugation. Bioadhesion was evaluated by determinating the contents of insulin in the gastrointestinal tract. The cytotoxicity of blank PLGA nanoparticles was identified by MTT assay. RESULTS Nanoparticles showed a narrow size of distribution. The average sizes of PLGA adhesive nanoparticles and common nanoparticles were （124.7±11） and （136.6±13）nm respectively,and the Zeta potential were （-1.67±0.05） and （42.6±0.3）mV,respectively. The entrappment efficiency of the chitosan-coated nanoparticles was higher than that of the common nanoparticles and reached to （52.73±2.96）%. The total content of FITC-labeled insulin of adhesived nanopartices was higher than that of common nanoparticles and the ratio was increased to 1.31 times at 3 h. In addition,cytotoxicity evaluation by the MTT assay proved that no extra toxicity was introduced into the nanoparticles during the formulation preparation. CONCLUSION These results indicated chitosan-loaded PLGA nanoparticles may be used as the vector in oral drug delivery system for proteins and peptides.

关 键 词：胰岛素 纳米粒 聚乳酸-羟基乙酸共聚物 壳聚糖 

分 类 号：R944[医药卫生—药剂学]