期刊
JOURNAL OF DRUG TARGETING
卷 16, 期 10, 页码 758-772出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10611860802473154
关键词
Dual drug therapy; folate-based targeting; receptor up-regulation; MTT cytotoxicity; receptor up-regulation assay
资金
- India Council of Technical Education (AICTE), New Delhi
- Indian Council of Medical Research (ICMR), New Delhi (India)
The present study is aimed at developing and evaluating a combined strategy of dual drug delivery, receptor up-regulation, and drug targeting. The dendritic architectures were synthesized and characterized by IR, 1H-NMR, and 13C-NMR spectroscopy. The pH-responsive simultaneous release behavior of the loaded bioactive from the carrier was also explored. The cell line studies for MTT cytotoxicity, receptor blockade, and receptor up-regulation assays were performed on HeLa cells. Treatment of cells with low concentration of all-trans retinoic acid (ATRA, 1M) caused a selective up-regulation of folate receptors by 2.21-folds when compared with that of untreated control, after 48h. ATRA showed a lag phase of 12h in up-regulating the folate receptors. After 48h, the IC50 value of naked methotrexate (MTX)-ATRA combination and dendrimer-loaded MTX-ATRA combination were found to be 0.1 and 10M, respectively, while folate-anchored dendrimer loaded with MTX-ATRA showed a selectively lowered IC50 value of 0.04M. It was concluded that in allied ailments like cancer, the proposed dual-drug delivery modality bearing anti-cancer bioactive in conjunction with folate receptor up-regulating cargo may prove to be a promising approach toward the development of a flourishing cancer therapy.
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