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目的优化盐酸阿霉素聚乳酸纳米粒(DOX-PLA-NPs)的制备工艺,并对其理化性质、体外释放及大鼠体内药动学进行研究。方法采用改良的复乳-溶剂挥发法制备DOX-PLA-NPs,正交设计优化其处方工艺,对其纳米粒形态、粒径、Zeta电位、包封率与载药量进行测定。以DOX原药为对照组,考察DOX-PLA-NPs的体外释药特性及大鼠尾静脉给药后的体内药动学参数。结果 DOX-PLA-NPs外观圆整,平均粒径为(125.67±3.80)nm、Zeta电位为(-35.97±1.58)m V、包封率和载药量分别为(81.23±1.46)%,(10.29±0.63)%。体外释放结果显示,DOX经纳米粒包裹后,具明显的缓释作用。DOX原药和纳米粒的体内药动学过程均符合开放式二室模型,t1/2β分别为(1.15±0.175)h、(6.43±2.12)h,CL分别为(174.76±47.22)h·L~(-1)、(30.68±11.86)h·L~(-1),AUC0→t分别为(6.01±1.61)μg·h·L~(-1)、(36.04±13.72)μg·h·L~(-1)。结论制备的盐酸阿霉素聚乳酸纳米粒粒径较小、包封率较高,具明显的缓释作用,并能提高药物的生物利用度。
OBJECTIVE To optimize the preparation process of doxorubicin-loaded polylactic acid (DOX-PLA-NPs) nanoparticles and study their physico-chemical properties, in vitro release and pharmacokinetics in rats. Methods DOX-PLA-NPs were prepared by a modified double emulsion-solvent evaporation method. The formulation was optimized by orthogonal design. The morphology, particle size, Zeta potential, entrapment efficiency and drug loading of nanoparticles were determined. DOX-PLA-NPs were used as control group to study the in vitro release characteristics of DOX-PLA-NPs and the in vivo pharmacokinetic parameters of rats after tail vein administration. RESULTS: The appearance of DOX-PLA-NPs was round and the average particle diameter was (125.67 ± 3.80) nm. The Zeta potential was -35.97 ± 1.58 mV. The encapsulation efficiency and drug loading of DOX-PLA-NPs were 81.23 ± 1.46% 10.29 ± 0.63)%. The results of in vitro release showed that DOX had obvious sustained release after being encapsulated by nanoparticles. The in vivo pharmacokinetics of DOX and NPs were in accordance with the open two-compartment model with t1 / 2β of (1.15 ± 0.175) h and (6.43 ± 2.12) h and CL of (174.76 ± 47.22) h · L (6.01 ± 1.61) μg · h · L -1, (36.04 ± 13.72) μg · h · (-1) and (30.68 ± 11.86) h · L -1, respectively L ~ (-1). Conclusion The prepared doxorubicin-loaded polylactic acid nanoparticles have the advantages of smaller particle size, higher entrapment efficiency, and obvious slow-release effect, and can improve the bioavailability of the drug.