醋酸地塞米松聚乙二醇化纳米粒的制备及兔体内药动学研究

Preparation and in vivo pharmacokinetics of polyethylene glycol-modified nanoparticles loaded with dexamethasone acetate

目的:制备醋酸地塞米松聚乙二醇(PEG)化纳米粒,并测定其在兔体内的药动学参数。方法:以高压均质法制备醋酸地塞米松PEG化纳米粒,用扫描电镜观察纳米颗粒的形态,用激光粒度分析仪测定粒径。建立检测血浆中醋酸地塞米松浓度的HPLC法,以醋酸地塞米松溶液和普通纳米粒作为对照,测定醋酸地塞米松PEG化纳米粒在兔体内的药动学参数。结果:PEG化纳米粒平均粒径为(180±7)nm。体内半衰期为4.79h,AUC0～12为11.81mg.min.L-1,平均滞留时间为3.15h,重要药动学参数比普通纳米粒及溶液剂增加近1倍。结论:醋酸地塞米松PEG化纳米粒可以延长醋酸地塞米松在兔体内的半衰期,达到体内长循环的目的;其表观特征与普通载药纳米粒无明显差异。

Objective：To prepare polyethylene glycol（PEG）-modified nanoparticles loaded with dexamethasone acetate and investigate its in vivo pharmacokinetics in rabbits.Methods：The nanoparticles were prepared by high pressure homogenization method.Their morphology was observed with scanning electron microscope and grain size was determined by laser grain size analyzer.HPLC method was employed to determine the plasma concentration of dexamethasone acetate.The pharmacokinetics of PEG-modified nanoparticles of dexamethasone acetate in rabbits were studied with dexamethasone acetate solution and general nanoparticles as control samples.Results：Grain sizes of the PEG-modified nanoparticles of dexamethasone acetate were（180±7） nm.The main pharmacokinetic parameters were as follows：t1/2β 4.79 h,AUC0-12 11.81 mg.min.L-1 and mean retain time（MRT） 3.15 h.They were almost twice as those of the solution and the general nanoparticles.Conclusion：There is no significant difference in the apparent characteristics between general and PEG-modified nanoparticles of dexamethasone acetate.PEG modification can prolong the in vivo circulation time of dexamethasone acetate nanoparticles.