The targeting of 14-succinate triptolide-lysozyme conjugate to proximal renal tubular epithelial cells.
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.
Zhang
Zhirong
Z
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan 610041, PR China. zrzzl@vip.sina.com
Zheng
Qiang
Q
Han
Jing
J
Gao
Guangping
G
Liu
Jie
J
Gong
Tao
T
Gu
Zhongwei
Z
Huang
Yuan
Y
Sun
Xun
X
He
Qin
Q
D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008297:Male; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D010616:Phenanthrenes / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013386:Succinates / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution
D004224:Diterpenes; D004337:Drug Carriers; D004852:Epoxy Compounds; D010616:Phenanthrenes; D013386:Succinates; C001899:triptolide; D009113:Muramidase