Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 36, Issue 2, Pages 387-391Publisher
ELSEVIER
DOI: 10.1016/j.jpba.2004.06.012
Keywords
oligodeoxynucleotide-doxorubicin conjugate; uptake; intracellular level; determination
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Bifunctional oligodeoxynucleotide-intercalator conjugates provide new tools for a selective control of gene expression and may have potential applications as novel therapeutic agents. An 'in situ' analysis method has been developed to determine intracellular levels of oligodeoxynucleotide-doxorubicin conjugate which may be used to reverse the multidrug resistance in KB-A-1 cells. A linear response over a broad concentration range (0.05-6.0 muM, r(2) = 0.97) was obtained. The limit of detection and quantitation was set at 0.015 and 0.05 muM, respectively. Assay validation studies revealed that compared with HPLC, the method is rapid, high simple, high throughput and convenient for the determination of the conjugate in cells in situ. The uptake studies of the conjugate in cells using this method demonstrated that the cellular accumulation of the conjugate in KB-A-1 cells was dependent on a dynamic balance between influx and efflux processes. (C) 2004 Elsevier B.V. All rights reserved.
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