Journal
BIOMATERIALS
Volume 30, Issue 7, Pages 1372-1381Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.11.035
Keywords
PTEC targeting; Triptolide; TPS-LZM conjugate; Immunological renal diseases
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We have synthesized a renal-specific drug carrier, 14-succinyl triptolide-lysozyme (TPS-LZM) conjugate for targeted delivery of TP to the PTECs. TPS-L2M 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 3.08 h to 4.10 h. At very low concentration, TPS-LZM could significantly reverse the disease progression in renal ischemia-reperfusion (1/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 Tf) 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. (c) 2008 Elsevier Ltd. All rights reserved.
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