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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 investigate the bioadhesive properties of chitosan-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles and to elucidate the mechanism of its absorption and investigate the cytotoxicity of nanoparticles to evaluate its safety. Methods Insulin was used as a model drug, FITC-labeled insulin was used to prepare normal PLGA nanoparticles, and chitosan was coated to prepare bioadhesive PLGA nanoparticles. Particle size and surface potential analyzer to measure the particle size and Zeta potential of nanoparticles, ultracentrifugation method to determine the entrapment efficiency of drug-loaded nanoparticles, to assess the bioadhesion of the nanoparticles by measuring the total amount of insulin in the gastrointestinal tract, and MTT assay The cytotoxicity of PLGA nanoparticles was evaluated. Results The average diameters of PLGA nanoparticles and bioadhesive nanoparticles were (124.7 ± 11) nm and (136.6 ± 13) nm, respectively. The differences in particle size were not significant, but the average particle size of chitosan coating was significantly The electropositive potential of nanoparticles increased from negative (-1.67 ± 0.05) mV to positive (42.6 ± 0.3) mV, and the encapsulation efficiency of the nanoparticles increased from (46.67 ± 1.82)% To (52.73 ± 2.96)%. Bioadhesive nanoparticles after oral administration of the total amount of insulin in the gastrointestinal tract was significantly higher than ordinary nanoparticles, reached a 1.31 times 3h. MTT method showed that bioadhesive PLGA nanoparticles and ordinary PLGA nanoparticles in the investigated dose range (≤ 25mg.mL-1), no special toxicity to the cells. Conclusion Chitosan-modified PLGA bioadhesive nanoparticles are good carriers for the oral administration of protein peptides.