TP-CSO: A Triptolide Prodrug for Pancreatic Cancer Treatment.
Molecules
; 27(12)2022 Jun 08.
Article
em En
| MEDLINE
| ID: mdl-35744811
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.
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MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Fenantrenos
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Pró-Fármacos
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Quitosana
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Diterpenos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article