Novel thermosensitive polymeric micelles for docetaxel delivery

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Abstract
Targeted delivery of antitumor drugs triggered by hyperthermia has significant advantages in clinical applications, since it is easy to implement and side effects are reduced. To release drugs site‐specifically upon local heating often requires the drugs to be loaded into a thermosensitive polymer matrix with a low critical solution temperature (LCST) between 37 and 42°C. However, the LCSTs of most thermosensitive materials were below 37°C, which limits their application in clinic because they would precipitate once injected into human body and lost thermal targeting function. Herein, we prepared a novel thermosensitive copolymer (poly(N‐isopropylacrylamide‐co‐acrylamide)‐b‐poly (DL‐lactide)) that exhibits no obvious physical change up to 41°C when heated. Docetaxel loaded micelles made of such thermosensitive polymer were prepared by dialysis method and the maximum loading content was found to be up to 27%. The physical properties, such as structure, morphology, and size distribution of the micelles with and without docetaxel were investigated by NMR, X‐ray diffraction, dynamic light scattering, atomic force microscopy, etc. The efficacy of this drug delivery system was also evaluated by examining the proliferation inhibiting activity against different cell linesin vitro. After hyperthermia, the cytotoxicity of docetaxel‐loaded micelles increased prominently. Our results demonstrated that this copolymer could be an ideal candidate for thermal targeted antitumor drug delivery. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

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