羟丝肽口服PLGA纳米粒的制备、体外释药及体内药物代谢动力学研究

Preparation, in vitro release and pharmacokinetics of JBP 485-loaded PLGA nanoparticles for oral delivery

目的以生物可降解材料乳酸-乙醇酸共聚物(PLGA)制备羟丝肽(JBP 485)纳米粒,并考察其形态、体外释放及体内药物代谢动力学性质。方法采用复乳(W/O/W)-溶剂挥发法制备了JBP 485-PLGA纳米粒;用透射电镜观察纳米粒的形态,并对JBP 485-PLGA纳米粒的粒径与分布、载药量、包封率和体内外释药进行了研究。结果制得的JBP 485-PLGA纳米粒为类球形实体粒子,平均粒径为93nm,多分散指数(PDI)为0.167,载药量约为8%,包封率约为30%。经大鼠口服灌胃后,JBP 485水溶液组在体内半衰期(t1/2)仅为1.47 h,t_(max)为1 h,AUC为10.286μg·h·mL^(-1),而同剂量的JBP 485-PLGA纳米粒在体内t1/2为4 h,t_(max)为2 h,AUC为17.157μg·h·mL^(-1)。结论制得的JBP 485-PLGA纳米粒可改变JBP 485体内的药物代谢动力学行为,延长JBP 485在体内的循环时间,具有明显的缓释作用,口服吸收好,生物利用度有明显提高。

Objective To prepare JBP 485 loaded nanoparticles （NPs） with biodegradable materials-poly （L- lactic-co-glycolic acid） （PLGA）, and to determine the shape characteristics and its release characteristics in vitro and its pharmacokinetics in rats. Methods JBP 485 loaded nanoparticles were made by double emulsion （W/O/ W）-solvent evaporation method. The shape characteristics of NPs was measured by TEM. The particles size, zeta potential, drug-loading capability, and entrapment efficiency were evaluated. The drug in vitro release and its pharmacokinetics in rats were investigated and compared with JBP 485 solution at the same time. Results The JBP 485 loaded PLGA nanoparticles were spheric with the mean size of 93 nm and the polydispersity of 0.167. The entrapment efficiency and drug-loading capability were about 30% and 8%, respectively. After oral JBP 485 solution and JBP 485-PLGA NPs in the rats, in the control group, the tl/2, tmax and A UC of JBP 485 solution were 1.47 h, 1 h and 10.286 μg · h · mL- 1, respectively. While the tl/2, tmax andAUC of JBP 485 PLGA NPs were 4 h, 2 h and 17.157 μg · h · mL - 1, respectively. Conclusion JBP 485 can be encapsuled in PLGA nanoparticles and the JBP 485-loaded PLGA NPs show significant sustained release in vivo. JBP 485-PLGA NPs can change the pharmacokinetics of JBP 485, prolong the circulation time in vivo and improve the bioavailability.