The effects of mixed MPEG-PLA/Pluronic (R) copolymer micelles on the bioavailability and multidrug resistance of docetaxel

Title
The effects of mixed MPEG-PLA/Pluronic (R) copolymer micelles on the bioavailability and multidrug resistance of docetaxel
Author(s)
최한곤용철순김대덕[김대덕]심창구[심창구]정석재[정석재]프라바챵펜무[챵펜무]후테 큐[후테 큐]영메윈[영메윈]이용복[이용복]
Keywords
BREAST-CANCER CELLS; DRUG-DELIVERY; POLYMERIC MICELLES; BLOCK-COPOLYMERS; DIBLOCK COPOLYMERS; AQUEOUS-SOLUTION; TUMOR-CELLS; SOLUBILIZATION; PEG; PACLITAXEL
Issue Date
201002
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v.31, no.8, pp.2371 - 2379
Abstract
A mixed micelle that comprised of MPEG-PLA (MPP) and Pluronic (R) copolymers was developed for enhanced bioavailability and to overcome multidrug resistance of docetaxel in cancer therapy. The mixed micelles that sufficiently solubilized docetaxel were evaluated for the effect of Pluronic (R) copolymers weight ratio on the mixed micelles with respect to drug loading and drug release. In vitro, cell viability and cytotoxicity studies in KB and KBv cells revealed that the mixed micellar formulations were more potent than the commercial docetaxel formulation (Taxotere (R)). In vivo pharmacokinetics study in rats showed that the mixed micelles significantly enhanced the bioavailability of docetaxel (3.6 fold) than Taxotere (R). Moreover, antitumor activity assessed in KBv cancer xenograft BALB/C nude mice models showed that the mixed micelles significantly reduced the tumor size than the control (Taxotere (R)). Clear differences in the intracellular uptake of docetaxel between MPP and mixed micelles were observed using confocal laser scanning microscopy. This study presents not only a new micelle structure for a diblock-triblock copolymer system, but also a method for enhanced bioavailability of docetaxel and to overcome some of the limitations on its multidrug resistance in cancer therapy. (C) 2009 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/22922http://dx.doi.org/10.1016/j.biomaterials.2009.11.102
ISSN
0142-9612
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약학대학 > 약학부 > Articles
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