Highly Water-Soluble Methotrexate-Polyethyleneglycol-Rhodamine Prodrug Micelle for High Tumor Inhibition Activity


Highly water-soluble prodrug micelle (50-fold compared with free MTX) of methotrexate-polyethyleneglycol-rhodamine (MTX-PEG-rhodamine) and MTX-mPEG was synthesized by the esterification reaction. The stability of the prodrug micelles was evaluated in phosphate buffer saline (PBS) with 10% fetal bovine serum (FBS). The tumor volume of the saline, MTX, and MTX-PEG-rhodamine groups was increased 3.7-fold, 2.8-fold, and 1.8-fold, respectively, compared with the initial tumor volume. TUNEL and drug distribution results further confirmed that the micelle of MTX-PEG-rhodamine possessed fewer side effects on the normal tissue compared with MTX. The prodrug micelle showed four advantages: retention of the drug activity site, higher water solubility of methotrexate (MTX), ease of preparation and application, and preferential accumulation in tumor tissues. These advantages of MTX-mPEG make it a promising drug delivery system (DDS) for clinical use.

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The authors express their sincere gratitude to the Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University and Professor Jie Kong for providing the experimental platform and funding.

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Correspondence to Xiao Duan or Lihua Song.

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All animal experimental procedures followed the institutional guidelines for the care and use of laboratory animals, and protocols were approved by the animal ethical and committee in the animal center of Changzhi Medical College, Shanxi, China.

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Duan, X., Yang, X., Li, C. et al. Highly Water-Soluble Methotrexate-Polyethyleneglycol-Rhodamine Prodrug Micelle for High Tumor Inhibition Activity. AAPS PharmSciTech 20, 245 (2019). https://doi.org/10.1208/s12249-019-1462-4

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  • prodrug micelle
  • biocompatible
  • drug activity
  • cancer therapy