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目的为了提高胰岛素口服给药的生物利用度制备生物黏附性聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,并与PLGA普通纳米粒相比较,考察纳米粒的理化性质、体外释放、生物活性及活体动物的体内分布。方法采用复乳法制备PLGA普通纳米粒,并经壳聚糖修饰制备生物黏附性纳米粒。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,HPLC测定体外释放特性,建立糖尿病模型大鼠评价口服纳米粒的降血糖水平,活动物成像系统观察口服纳米粒在小鼠体内的分布及转运。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(121.3±13)和(134.4±15)nm,Zeta电位分别为(-1.72±0.2)和(43.1±0.3)mV,包封率分别为(46.87±2.23)%和(52.76±3.48)%。纳米粒的体外释放由突释期和缓慢释放期组成,壳聚糖包裹的生物黏附性纳米粒减低了突释量,由(28.34±1.63)%降至(17.92±1.14)%;大鼠灌胃给予15 u.kg-1胰岛素,生物黏附性纳米粒的药理相对生物利用度与普通纳米粒相比具有显著性差异,由(8.3±0.7)%提高至(11.4±0.6)%。壳聚糖修饰的PLGA生物黏附性纳米粒具有生物黏附性且促吸收作用明显,口服给药后8 h仍在小鼠肠道中大量分布。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 prepare bioadhesive polylactic-co-glycolic acid (PLGA) nanoparticles for bioavailability of oral administration of insulin, and compared with conventional PLGA nanoparticles, the physical and chemical properties, in vitro release, biological activity and In vivo distribution of living animals. Methods Double PLGA nanoparticles were prepared by double emulsion method and bioadhesive nanoparticles were prepared by chitosan modification. Particle size and surface potential analyzer to measure the particle size and Zeta potential of nanoparticles; the entrapment efficiency of drug-loaded nanoparticles was measured by ultracentrifugation method, the in vitro release characteristics were determined by HPLC, and the diabetic model rats were established to evaluate the hypoglycemic level of oral nanoparticles, OBJECTIVE To observe the distribution and transport of oral nanoparticles in mice. Results The average diameter of PLGA nanoparticles was (121.3 ± 13) nm and (134.4 ± 15) nm, respectively. The average Zeta potential was (-1.72 ± 0.2) and (43.1 ± 0.3) mV, encapsulation efficiency was (46.87 ± 2.23)% and (52.76 ± 3.48)%, respectively. The in vitro release of nanoparticles from the burst release and slow release phase composition, chitosan-coated bioadhesive nanoparticles decreased burst release, from (28.34 ± 1.63)% to (17.92 ± 1.14)%; rat irrigation Stomach to give 15 u.kg-1 insulin. The bioavailability of bioadhesive nanoparticles was significantly increased from (8.3 ± 0.7)% to (11.4 ± 0.6)% compared with that of normal nanoparticles. Chitosan-modified PLGA bioadhesive nanoparticles with bioadhesive and absorption-promoting effect were obvious, and still distributed in the intestine of mice more than 8 h after oral administration. Conclusion Chitosan-modified PLGA bioadhesive nanoparticles are good carriers for the oral administration of protein peptides.