In vivoantitumor effects of carboxymethyl chitosan-conjugated triptolide after oral administration

被引：17

作者：

Zeng, Huahui ^{[1
,2
,3
]}

Zhu, Xin ^{[3
]}

Tian, Qikang ^{[3
]}

Yan, Yinyin ^{[3
]}

Zhang, Lan ^{[3
]}

Yan, Min ^{[1
]}

Li, Ruiqin ^{[1
]}

Li, Xiaofang ^{[1
]}

Wang, Guoqiang ^{[1
]}

Ma, Jinlian ^{[1
]}

Su, Yufang ^{[1
]}

Zhang, Xiangbo ^{[3
]}

Ma, Linyu ^{[3
]}

Zhang, Zhenqiang ^{[1
]}

Wu, Xiangxiang ^{[1
,3
]}

机构：

[1] Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450046, Peoples R China

[2] Henan Univ Chinese Med, Sch Basic Med, Zhengzhou, Peoples R China

[3] Henan Univ Chinese Med, Pharm Coll, Zhengzhou, Peoples R China

来源：

DRUG DELIVERY | 2020年 / 27卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Triptolide; carboxymethyl chitosan; oral administration; pancreatic cancer; toxicity; PANCREATIC-CANCER; CELL-DEATH;

D O I：

10.1080/10717544.2020.1770370

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The purpose of this study is to evaluatein vitro and in vivoantitumor efficacy and subacute toxicity of triptolide (TP) prodrug, a conjugate between TP and carboxymethyl chitosan (CC). The CCTP conjugate contained 4 similar to wt % TP and displayed excellent aqueous solubility (5 mg/mL) as compared to the native TP (17 mu g/mL).In vitrocytotoxicity of CCTP conjugate was evaluated by CCK8 assay against human pancreatic cancer (PC) cell lines, showing comparable the half maximal inhibitory concentration (IC50) values to the parent TP. In a mouse model of PC (BxPC-3), the CCTP conjugate administered orally (at dose levels as low as 0.2 mg TP equivalent/kg) showed comparable efficacy in reducing or eliminating xenograft tumor to the same dose of TP, but exhibited much lower subacute toxicity as seen in body weight loss and hematological toxicity.

引用

页码：848 / 854

页数：7

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