کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2484396 | 1114309 | 2015 | 7 صفحه PDF | دانلود رایگان |
ABSTRACT:Active drug targeting is an effective therapeutic approach for the treatment of malignant cancers and novel types of drug carriers have been developed. In this study, we developed a cyclodextrin (CD)-based novel carrier–drug conjugate, called per-FOL-β-CD-ss-DOX, which has folic acid (FA) molecules at the end of primary hydroxyl groups of β-CD and a pH-cleavable spacer with an anticancer drug, doxorubicin (DOX), at the end of secondary hydroxyl groups. This per-FOL-β-CD-ss-DOX exhibited a significant cellular uptake as compared with the free DOX solution by EMT6/P cells, which activate the expression of folate receptor (FR). Cellular uptake of per-FOL-β-CD-ss-DOX was significantly inhibited in the presence of FA and was also inhibited at 4 °C. The conjugate exhibited remarkable cytotoxic effects in EMT6/AR1 cells, which are resistant to DOX, whereas free DOX solution did not exhibit this effect. These results suggest that per-FOL-β-CD-ss-DOX can be taken up into cells via FR-related endocytosis and the cleaved DOX derived from it in endosomes could escape the efflux caused by P-glycoprotein, resulting in the cytotoxic effect. Therefore, the drug delivery by per-FOL-β-CD-ss-DOX may be a useful approach for drug delivery to FR-expressing cells such as drug-resistant malignant cancers.
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 9, September 2015, Pages 2934–2940