大黄酸聚乳酸纳米粒的制备及大鼠体内药动学研究

 目的 制备大黄酸聚乳酸纳米粒，并考察其在大鼠体内的药动学特征，以期提高大黄酸口服生物利用度。方法 以聚乳酸为载体材料，采用改良的自乳化溶剂扩散法制备大黄酸聚乳酸纳米粒；透射电镜观察纳米粒的形态；激光粒度仪考察粒径和Zeta电位；超速离心法测定其包封率及载药量；透析袋法研究其体外释药特性；以大黄酸混悬液为对照组，进行大鼠口服大黄酸聚乳酸纳米粒的药动学研究。结果 纳米粒外观呈圆形或类圆形，平均粒径为（134.37±3.61）nm，Zeta电位为（-18.41±0.07） mV，包封率和载药量分别为（60.37±1.52）%和（1.32±0.09）%；体外释药符合Higuchi方程；大鼠口服大黄酸混悬液和纳米粒后，ρ_max分别为（5.788±0.15）和（11.607±0.56）mg·L^-1，t_max分别为（0.193±0.01）和（1.102±0.13）h， AUC_0→t分别为（8.077±2.98）和（34.583±3.93）mg·h·L^-1，t_1/2β分别为（3.319±0.23）和（21.721±6.13）h。结论 聚乳酸纳米粒可显著改善大黄酸的药动学行为，有效提高其口服生物利用度。

Study on Preparation and Pharmacokinetics of Rhein-Loaded Polylactic Acid Nanoparticles

OBJECTIVE To prepare rhein-loaded polylactic acid nanoparticles,and investigate their physicochemical properties,release behavior in vitro and pharmacokinetics in vivo in rats.METHODS Rhein-loaded polylactic acid nanoparticles were prepared by a modified spontaneous emulsificationsolvent diffusion method with PLA as the carrier.The morphology of rhein-loaded polylactic acid nanoparticles was observed by transmission electron microscope.Mean particle size and Zeta potential were estimated by laser particle size analyzer.Entrapment efficiency and drug loading were investigated by ultracentrifugation.Drug release behavior in vitro was studied by dialysis.Using rhein aqueous suspension as control,the pharmacokinetic behavior of rhein-loaded polylactic acid nanoparticles after oral administration in rats were studied.RESULTS The shape of rhein-loaded polylactic acid nanoparticles was spherical.The mean particle size,Zeta potential,entrapment efficiency and drug loading were(134.37±3.61) nm,(-18.41±0.07) mV,(60.37±1.52)% and(1.32±0.09)%,respectively.The profiles of release were fitted well by Higuchi equation.Results of pharmacokinetic study showed that the ρmax of rhein suspension and rhein-loaded polylactic acid nanoparticles were(5.788±0.15) and(11.607±0.56) mg·L-1,tmax were(0.193±0.01) and(1.102±0.13) h,AUC0→t were(8.077±2.98) and(34.583±3.93)mg·h·L-1,t1/2β were(3.319±0.23) and(21.721±6.13) h,respectively.CONCLUSION Polylactic acid nanoparticles can effectively improve the pharmacokinetic behaviour and oral bioavailability of rhein.