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In vivo antitumor effects of carboxymethyl chitosan-conjugated triptolide after oral administration.
- Source :
-
Drug delivery [Drug Deliv] 2020 Dec; Vol. 27 (1), pp. 848-854. - Publication Year :
- 2020
-
Abstract
- The purpose of this study is to evaluate in vitro and in vivo 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). In vitro cytotoxicity of CCTP conjugate was evaluated by CCK8 assay against human pancreatic cancer (PC) cell lines, showing comparable the half maximal inhibitory concentration (IC <subscript>50</subscript> ) 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.
- Subjects :
- Administration, Oral
Animals
Antineoplastic Agents, Alkylating pharmacology
Antineoplastic Agents, Alkylating toxicity
Biocompatible Materials pharmacology
Cell Line, Tumor
Chitosan pharmacology
Drug Carriers
Drug-Related Side Effects and Adverse Reactions prevention & control
Epoxy Compounds pharmacology
Epoxy Compounds toxicity
Humans
Inhibitory Concentration 50
Mice
Pancreatic Neoplasms drug therapy
Prodrugs pharmacology
Solubility
Treatment Outcome
Xenograft Model Antitumor Assays
Chitosan analogs & derivatives
Diterpenes pharmacology
Diterpenes toxicity
Phenanthrenes pharmacology
Phenanthrenes toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0464
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Drug delivery
- Publication Type :
- Academic Journal
- Accession number :
- 32508161
- Full Text :
- https://doi.org/10.1080/10717544.2020.1770370