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TP-CSO: A Triptolide Prodrug for Pancreatic Cancer Treatment.

ABSTRACT: Triptolide (TP) is a potential drug candidate for the treatment of cancer, but its use was hampered by its systemic toxicity and poor water solubility. Hence, a TP-CSO prodrug was synthesized by conjugating TP to chitosan oligosaccharide (CSO), and characterized by ¹H NMR, FTIR, DSC and XRD analyses. The TP-CSO containing about 4 wt% of TP exhibited excellent water solubility (15 mg/mL) compared to TP (0.017 mg/mL). Compared with TP, the pharmacokinetics of the conjugate after oral administration showed a three-fold increase in the half-life in the blood circulation and a 3.2-fold increase in AUC _(0-∞). The orally administered TP-CSO could more effectively inhibit tumor progression but with much lower systemic toxicity compared with TP, indicating significant potential for further clinical trials. In conclusion, CSO-based conjugate systems may be useful as a platform for the oral delivery of other sparingly soluble drugs.

SUBMITTER: Wang X

PROVIDER: S-EPMC9227231 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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TP-CSO: A Triptolide Prodrug for Pancreatic Cancer Treatment.

Wang Xinlong X Zeng Huahui H Zhu Xin X Xu Duanjie D Tian Qikang Q Wang Can C Zhao Lingzhou L Zhao Junwei J Miao Mingsan M Wu Xiangxiang X

Molecules (Basel, Switzerland) 20220608 12

Triptolide (TP) is a potential drug candidate for the treatment of cancer, but its use was hampered by its systemic toxicity and poor water solubility. Hence, a TP-CSO prodrug was synthesized by conjugating TP to chitosan oligosaccharide (CSO), and characterized by <sup>1</sup>H NMR, FTIR, DSC and XRD analyses. The TP-CSO containing about 4 wt% of TP exhibited excellent water solubility (15 mg/mL) compared to TP (0.017 mg/mL). Compared with TP, the pharmacokinetics of the conjugate after oral ad ...[more]

PMID: 35744811

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