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• W3207576565 endingPage "2745" @default.
• W3207576565 startingPage "2745" @default.
• W3207576565 abstract "Docetaxel (DTX) is among the most frequently prescribed chemotherapy drugs and has recently been shown to extend survival in advanced prostate cancer patients. However, the poor water solubility of DTX prevents full exploitation of this potent anticancer drug. The current marketed formulation, Taxotere®, contains a toxic co-solvent that induces adverse reactions following intravenous injection. Nano-sized polymeric micelles have been proposed to create safer, water-soluble carriers for DTX, but many have failed to reach the clinic due to poor carrier stability in vivo. In this study, we aimed to improve micelle stability by synthesizing an ester prodrug of DTX, oligo(lactic acid)8-docetaxel (o(LA)8-DTX), for augmented compatibility with the core of poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) micelles. Due to the enhancement of drug-carrier compatibility, we were able to load 50% (w/w) prodrug within the micelle, solubilize 20 mg/mL o(LA)8-DTX (~12 mg/mL DTX-equivalent) in aqueous media, and delay payload release. While the micelle core prohibited premature degradation, o(LA)8-DTX was rapidly converted to parent drug DTX through intramolecular backbiting (t1/2 = 6.3 h) or esterase-mediated degradation (t1/2 = 2.5 h) following release. Most importantly, o(LA)8-DTX micelles proved to be as efficacious but less toxic than Taxotere® in a preclinical mouse model of prostate cancer." @default.
• W3207576565 created "2021-10-25" @default.
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• W3207576565 date "2021-10-17" @default.
• W3207576565 modified "2023-09-27" @default.
• W3207576565 title "Oligo(Lactic Acid)8-Docetaxel Prodrug-Loaded PEG-b-PLA Micelles for Prostate Cancer" @default.
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• W3207576565 doi "https://doi.org/10.3390/nano11102745" @default.
• W3207576565 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8540550" @default.
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• W3207576565 hasPublicationYear "2021" @default.
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