Kidney-Targeted Triptolide-Encapsulated Mesoscale Nanoparticles for High-Efficiency Treatment of Kidney Injury

Bad water solubility and undesired toxicity of triptolide (TP) still restrict its clinical applications in renal diseases. In this work, well-defined, monodispersed and uniform-sized TP-encapsulated mesoscale nanoparticles (TP-MNPs) were fabricated through a nanoprecipitation method, which had specially kidney-targeted capacity, slow-release property and high-efficiency treatment for renal ischaemia-reperfusion injury (IRI). The TP-MNPs had good cytocompatibility in wide TP concentration (0-500 ng/ml) and time ranges (6-24 h). Ex vivo organ fluorescence imaging and pharmacokinetics analysis suggested that TP-MNPs possessed excellent kidney-targeted capability with long retention time (7 days). The TP-MNPs with a very low dose of TP (0.01 mg/kg) could protect effectively kidney against IRI, while 0.01 mg/kg TP was completely ineffective. After treated with TP-MNPs, serum creatine, blood urea nitrogen, expression of C3 complement and phosphoextracellular signal-regulated kinase of renal IRI mice were 5.9-, 2.0-, 5.4- and 2.8-fold lower than those of the mice treated with TP, respectively. Compared with TP, the TP-MNPs exhibited ignorable hepatotoxicity, reproductive toxicity and immunotoxicity, such as lower alanine aminotransferase (0.5-fold) and aspartate aminotransferase (0.2-fold) and higher ratio of CD4+/CD8+ (2.2-fold). The monodispersed and uniform-sized TP-MNPs with special kidney-targeting and slow-release property may pave an avenue for designing a new therapeutic strategy for renal diseases.