1. The targeting of 14-succinate triptolide-lysozyme conjugate to proximal renal tubular epithelial cells
- Author
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Zhang, Zhirong, Zheng, Qiang, Han, Jing, Gao, Guangping, Liu, Jie, Gong, Tao, Gu, Zhongwei, Huang, Yuan, Sun, Xun, and He, Qin
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DRUG carriers , *TARGETED drug delivery , *LYSOZYMES , *KIDNEY tubules , *EPITHELIAL cells , *DRUG delivery systems , *HEPATOTOXICOLOGY - Abstract
Abstract: We have synthesized a renal-specific drug carrier, 14-succinyl triptolide-lysozyme (TPS-LZM) conjugate for targeted delivery of TP to the PTECs. TPS-LZM could be taken up by HK-2 cells, free TP would be degraded and released, mainly from basolateral side of the cells. Compared with TP, the overall targeting efficiency (TE) of TPS-LZM was significantly enhanced from 11.74% to 95.54% and its MRT was moderately prolonged from 3.08h to 4.10h. At very low concentration, TPS-LZM could significantly reverse the disease progression in renal ischemia-reperfusion (I/R) injury animal models, while the mixture of free TP and LZM was ineffective. Further, TPS-LZM conjugate presented much lower hepatotoxicity (0.78 folds lower than TP) and no adverse effect on the immune (1.13 folds higher than TP) and genital system. Thus, TPS-LZM represents a very effective drug candidate for specific treatment of immunological renal diseases with low adverse side effect. [Copyright &y& Elsevier]
- Published
- 2009
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