Preparation of Doxorubicin-loaded PLA Nanoparticles and Study Their Pharmacokinetics in Rats

OBJECTIVE To optimize the preparation of doxorubicin-loaded PLA nanoparticles (DOX-PLA-NPs), and evaluate their physicochemical properties, release behavior in vitro and study their pharmacokinetics in rats. METHODS The DOX-PLA-NPs were prepared by modified double emulsification(W/O/W) solvent evaporation method. Orthogonal test was used to optimize the preparation procedure. The morphology, size distribution, Zeta potential, encapsulation efficiency, and drug loading of DOX-PLA-NPs were characterized. The drug release behavior in vitro and pharmacokinetics behavior in vivo was investigated in comparison with DOX-sol. RESULTS The optimized nanoparticles were spherical in shape with the mean particle size of (125.67±3.80)nm and the Zeta potential of (-35.97±1.58)mV. The encapsulation efficiency and drug loading were (81.23±1.46)%, (10.29±0.63)%, respectively. In vitro drug release results showed DOX-PLA-NPs had a sustained release character. In in vivo study, the pharmacokinetic behavior of DOX-sol and DOX-PLA-NPs were best fitted to two-compartment model and the parameters were as follows:t_1/2β (1.15±0.175)h, (6.43±2.12)h, CL(174.76±47.22) h·L^-1, (30.68±11.86)h·L^-1, AUC_0→t(6.01±1.61)μg·h·L^-1, (36.04±13.72)μg·h·L^-1. CONCLUSION The optimized DOX-PLA-NPs is practicable with small particle size, high encapsulation efficiency, a certain sustained release characteristic and can significantly improve the bioavailability after vein injection.