[Preparation and toxicity of triptolide-loaded poly (D,L-lactic acid) nanoparticles].

Aim: Investigations on reducing the toxicity of triptolide through poly(D, L-lactic acid) nanoparticles as a drug carrier by oral administration to Wistar rats.

Methods: Triptolide-loaded poly (D, L-lactic acid) nanoparticles (TP-PLA-NPs) were prepared by modified spontaneous emulsification solvent diffusion (modified-SESD). The shape of nanoparticles was observed by transmission electron microscope (TEM). The size distribution and mean diameter were measured by laser light scattering technique. The entrapment efficiency and contents of drug loading were determined by RP-HPLC. The physical state of drug loaded in nanopartiles were primarily investigated by X-ray powder diffractometry. TP-PLA-NPs release behavior in vitro was carried out. After oral administration of the nanoparticles to Wistar rats in 15d, the toxicity for liver and kidney were studied by determining aspartate transaminase (AST), alanine transaminase (ALT) and blood urea nitrogen in serum and concentration of protein in urine.

Results: The preparation process adapted to the formulation was as follows: the volume ratio of the aqueous and organic phases was 40/15; the surfactant concentration was 1%; the drug concentration was 0.3%; triptolide-PLA was 1:15 (w/w). The mean diameter was 149.7 nm and the polydispersity index was 0. 088 for the nanoparticles prepared by above conditions. The entrapment efficiency and content of drug loading were 74.27% and 1.36%, respectively. The release behavior of drug in vitro showed an initial burst effect, subsequently a slower rate stage. The results indicated that the liver toxicity (P < 0.01) and kidney toxicity (P < 0.05) caused by triptolide could be decreased significantly by nanoparticles carrier.

Conclusion: PLA-NPs might be used as a new oral carrier for triptolide.