Kidney-targeted triptolide-encapsulated mesoscale nanoparticles for high-efficiency treatment of kidney injury. (16th October 2019)

• Record Type: Journal Article
• Authors: Deng, Xiulong; Zeng, Tao; Li, Jiawen; Huang, Caili; Yu, Meng; Wang, Xin; Tan, Lishan; Zhang, Mengbi; Li, Aiqing; Hu, Jianqiang
• Is Part Of: Biomaterials science. Volume 7:Number 12(2019)
• Page Start: 5312
• Page End: 5323
• Publication Date: 2019-10-16
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c9bm01290g
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Insolubility and toxicity of TP restrict clinical applications in renal diseases. Here, TP-encapsulated mesoscale nanoparticles offer a new therapeutic strategy for renal diseases due to good biocompability, kidney targeting and slow release. Abstract : 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 possesses special kidney-targeting 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 −1 ) and time ranges (6–24 h). Ex vivo organ fluorescence imaging and pharmacokinetic analysis suggested that TP-MNPs possessed excellent kidney-targeting capability with long retention time (7 days). The TP-MNPs with a very low dose of TP (0.01 mg kg −1 ) could effectively protect the kidney against IRI, while 0.01 mg kg −1 TP was completely ineffective. After treatment with TP-MNPs, the serum creatine, blood urea nitrogen, expression of C3 complement, and phospho-extracellular signal-regulated kinase of renal IRI mice were estimated to be 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 a higher ratio of CD 4+ /CD 8+ (2.2 fold). Thus, 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.