enhanced cellular uptake and pharmacokinetic characteristics of doxorubicin-valine amide prodrug
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ID: 194872
2016
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Abstract
In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (1H-NMR) assay. In the MCF-7 cells (human breast adenocarcinoma cell; amino acid transporter–positive cell), the cellular accumulation efficiency of DOX-Val was higher than that of DOX according to the flow cytometry analysis data. Using confocal laser scanning microscopy (CLSM) imaging, it was confirmed that DOX-Val as well as DOX was mainly distributed in the nucleus of cancer cells. DOX-Val was intravenously administered to rats at a dose of 4 mg/kg, and the plasma concentrations of DOX-Val (prodrug) and DOX (formed metabolite) were quantitatively determined. Based on the systemic exposure (represented as area under the curve (AUC) values) of DOX-Val (prodrug) and DOX (formed metabolite), approximately half of DOX-Val seemed to be metabolized into DOX. However, it is expected that the remaining DOX-Val may exert improved cellular uptake efficiency in cancer cells after its delivery to the cancer region.
| Reference Key |
park2016moleculesenhanced
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|---|---|
| Authors | ;Yohan Park;Ju-Hwan Park;Suryeon Park;Song Yi Lee;Kwan Hyung Cho;Dae-Duk Kim;Won-Sik Shim;In-Soo Yoon;Hyun-Jong Cho;Han-Joo Maeng |
| Journal | Journal of ethnopharmacology |
| Year | 2016 |
| DOI |
10.3390/molecules21101272
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| URL | |
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