羟基喜树碱两亲性长循环纳米粒的药动学研究

 目的 制备羟基喜树碱的两亲性长循环纳米粒并进行初步的理化性质考察，研究了其在大鼠体内的药动学。方法 本实验合成了聚乙二醇-聚己内酯嵌段共聚物(PEG-PCL)，并以此为载体材料，采用溶剂扩散法制备了羟基喜树碱两亲性长循环纳米粒（HCPT-PEG-PCL-NPs)，对其进行初步的质量评价及稳定性考察，高效液相色谱法检测并比较了HCPT注射液和不同共聚物载体制备的羟基喜树碱两亲性长循环纳米粒在大鼠体内的药动学参数。结果 以共聚物PEG4000-PCL1250、PEG4000-PCL2000、PEG2000-PCL1250、PEG2000-PCL2000为载体制备的4种羟基喜树碱两亲性长循环纳米粒的平均粒径依次为110.0、116.1、99.1、119.9 nm，平均ξ电位依次为-16.9、-22.4、-28.8、-33.5mV，平均包封率依次为83.10%、88.29%、77.46%、80.67%，平均载药量依次为2.56%、2.96%、2.14%、2.31%；冻干粉剂的稳定性较好，但高温环境不利于保存。HCPT注射液t_1/2为0.141 8 h，以共聚物载体PEG4000-PCL1250、PEG4000-PCL2000、PEG2000-PCL1250、PEG2000- PCL2000制备的羟基喜树碱两亲性长循环纳米粒的t_1/2依次为它的18.07、9.08、5.25、5.14倍。结论 羟基喜树碱两亲性长循环纳米粒在体内有较好的长循环作用。

Pharmacokinetics of Amphiphilic Long-Circulating Hydroxycamptothecin Nanoparticles

OBJECTIVE To prepare amphiphilic long-circulating hydroxycamptothecin nanoparticles and investigate its physico-chemical properties and pharmacokinetic characteristics in rats.METHODS Polyethyleneglycol-polycaprolactone(PEG-PCL) was synthesized.HCPT-PEG-PCL-NPs were prepared by solvent-diffusion method using PEG-PCL block copolymer as the matrix.The obtained NPs were evaluated,and the physical stabilities of both suspl and freeze-dried powder were investigated.High-performance liquid chromatography(HPLC) was used to determine and compare the pharmacokinetic parameters of HCPT injection and HCPT-PEG-PCL-NPs prepared with different copolymers in rats.RESULTS When using PEG4000-PCL1250,PEG4000-PCL2000,PEG2000-PCL1250,PEG2000-PCL2000 as the carrier materials,the average particle sizes of NPs were 110.0,116.1,99.1 and 119.9 nm;the Zeta potentials were-16.9,-22.4,-28.8 and-33.5 mV;the entrapment efficiency were 83.10%,88.29%,77.46% and 80.67%;and the drug loading percentages were 2.56%,2.96%,2.14% and 2.31%,respectively.The physical stability of the freeze-dried powder was better,and hot environment seemed to be bad for the stability.The t1/2s of HCPT-PEG4000-PCL1250-NPs,HCPT-PEG2000-PCL1250-NPs,HCPT-PEG4000-PCL2000-NPs and HCPT-PEG2000-PCL2000-NPs were 18.07,9.08,5.25 and 5.14 times longer than that of HCPT injection which was 0.141 8 h.CONCLUSION The HCPT-PEG-PCL-NPs show sustained-release effect and long-circulation property compared with HCPT injection.