<i>In vivo</i> antitumor effects of carboxymethyl chitosan-conjugated triptolide after oral administration

Abstract

The purpose of this study is to evaluate <i>in vitro and in vivo</i> antitumor efficacy and subacute toxicity of triptolide (TP) prodrug, a conjugate between TP and carboxymethyl chitosan (CC). The CCTP conjugate contained 4∼ wt % TP and displayed excellent aqueous solubility (5 mg/mL) as compared to the native TP (17 μg/mL). <i>In vitro</i> cytotoxicity 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.