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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t1/2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t1/2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。
OBJECTIVE To prepare hydroxycamptothecin long-acting amphiphilic nanoparticles and study the physico-chemical properties of the amphiphilic nanoparticles. Methods Polyethylene glycol-polycaprolactone block copolymer (PEG-PCL) was synthesized in this experiment. Hydroxycamptothecin amphiphilic long circulating nanoparticles (HCPT) were prepared by solvent diffusion method -PEG-PCL-NPs). The initial quality evaluation and stability study of HCPT injection were carried out by HPLC. HCPT injection and amphoteric hydroxycamptothecin long-circulating nanoparticles prepared by different copolymer carriers were compared and evaluated. Pharmacokinetic parameters in rats. Results The average diameters of the four kinds of hydroxycamptothecin long-acting amphipathic hydroxyapatite nanoparticles prepared with copolymers PEG4000-PCL1250, PEG4000-PCL2000, PEG2000-PCL1250 and PEG2000-PCL2000 were 110.0,116.1,99.1 and 119.9 nm , The average zeta potential was -16.9, -22.4, -28.8 and -33.5 mV, respectively. The average entrapment efficiencies were 83.10%, 88.29%, 77.46% and 80.67%, and the average loading rates were 2.56%, 2.96% and 2.14 %, 2.31%. The stability of freeze-dried powder is better, but the high temperature environment is not conducive to preservation. The t1 / 2 of HCPT injection was 0.141 8 h. The t1 / 2 of hydroxycamptothecin amphipathic long circulating nanoparticles prepared with the copolymer carriers PEG4000-PCL1250, PEG4000-PCL2000, PEG2000-PCL1250 and PEG2000- 18.07,9.08,5.25,5.14 times. Conclusion Hydroxycamptothecin amphiphilic long circulating nanoparticles in the body has a good long-circulating effect.