羟基喜树碱长循环纳米粒的制备和体外释药研究

Preparation and In vitro Drug Release Study of Long-circulating Hydroxycamptothecin Nanoparticles

目的:制备羟基喜树碱的长循环纳米粒并进行体外释药性质考察。方法:合成了聚乙二醇-聚己内酯嵌段共聚物,并以此为载体材料,采用溶剂扩散法制备羟基喜树碱长循环纳米粒,对其进行表征及体外释药研究。结果:以共聚物PEG4000-PCL2000、PEG4000-PCL1250、PEG2000-PCL2000、PEG2000-PCL1250为载体制备的4种HCPT-PEG-PCL-NPs的平均粒径依次为116.1、110.0、119.9、99.1nm,平均ξ电位依次为-22.4、-16.9、-33.5、-28.8 mV,平均包封率依次为88.29%、83.10%、80.67%、77.46%,平均载药量依次为2.96%、2.56%、2.31%、2.14%;所制备的HCPT-PEG-PCL-NPs均具有一定的缓释作用,体外释药均符合Weibull分布模型,其释药机理应是药物的被动扩散与载体基质的溶蚀协同作用。结论:所制备的HCPT-PEG-PCL-NPs包封率和载药量较高,粒径分布均匀,体外释药具有缓释特点,为羟基喜树碱的临床应用提供了更广阔的前景。

Objective： To prepare long-circulating hydroxycamptothecin nanoparticles and study its in vitro drug release characteristics.Methods： The HCPT-PEG-PCL-NPs were prepared by solvent-diffusion method using PEG-PCL block copolymer synthesized as a matrix and HCPT as an antitumor agent.Then the obtained NPs were evaluated and its in vitro drug release characteristics were investigated.Results： When using PEG4000-PCL2000,PEG4000-PCL1250,PEG2000-PCL2000,PEG2000-PCL1250 as the carrier material to prepare NPs,the average particle size of NPs in turn were 116.1,110.0,119.9,99.1nm;the zeta potential were-22.4,-16.9,-33.5,-28.8 mV;the entrapment efficiency were 88.29%,83.10%,80.67%,77.46%;and the drug loading were 2.96%,2.56%,2.31%,2.14%,respectively.HCPT-PEG-PCL-NPs all showed a certain degree of sustained-release characteristics and their release mechanisms were fitted to Weibull modle,which showed that the drug release process included passive diffusion and matrix-eroded procedure.Conclusion： The HCPT-PEG-PCL-NPs has high entrapment efficiency,drug loading,uniform particle size,and can retard drug release in vitro,so it provides an extensive prospect for clinical application of HCPT.