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  • Title: PEG-PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapy.
    Author: Wang Y, Chen L, Tan L, Zhao Q, Luo F, Wei Y, Qian Z.
    Journal: Biomaterials; 2014 Aug; 35(25):6972-85. PubMed ID: 24836952.
    Abstract:
    In this study, a composite drug delivery system was developed and evaluated for oral delivery of docetaxel: docetaxel-loaded micelles in pH-responsive hydrogel (DTX-micelle-hydrogel). Docetaxel was successfully loaded in micelles with small particle size of 20 nm and high drug loading of 7.76%, which contributed to the drug absorption in the intestinal tract. The experiments of cytotoxicity on 4T1 cells demonstrated the effective antitumor activity of DTX micelles. Meanwhile, a pH-responsive hydrogel was synthesized and optimized for incorporating the docetaxel micelles. The pH-responsiveness and reversibility of the hydrogel were investigated under the pH conditions of the gastrointestinal tract. Furthermore, the DTX-micelle-hydrogel system showed much quicker diffusion of micelles in simulated intestinal fluid than in simulated gastric fluid, which was mainly caused by the change of pH value. The docetaxel released from the micelle-hydrogel system quite slowly, so it had little influence on the absorption of DTX micelles in small intestine. More important, the pharmacokinetic study revealed that the DTX-micelle-hydrogel significantly improved the oral bioavailability of docetaxel (75.6%) about 10 times compared to DTX micelles, and this increase in bioavailability was probably due to the small intestine targeting release of the pH-responsive hydrogel. Consequently, the oral DTX-micelle-hydrogel system was effective in inhibiting tumor growth in subcutaneous 4T1 breast cancer model, and decreased systemic toxicity compared with intravenous treatment. The apoptosis cells in the immunofluorescent studies and the proliferation-positive cells in the immunohistochemical studies were also consistent with the results. Therefore, the DTX-micelle-hydrogel system might be a promising candidate oral drug for breast cancer therapy.
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