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Preparation of mPEG-b-PLA/TM-2 Micelle Lyophilized Products by Mixed Lyoprotectors and Antitumor Effect In Vivo

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Abstract

The objective of this study was to encapsulate the poorly water-soluble drug TM-2 into polymer micelles using mPEG2k-b-PLA2.4k to increase its aqueous solubility and improve its therapeutic effect for liver cancer. Furthermore, in order to achieve long-term storage, the micelle solution was successfully freeze-dried. This study theoretically clarified the possibility of enhancing the water solubility of TM-2 using mPEG2k-b-PLA2.4k micelles as well as the protective effects of mixed lyoprotectants. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were performed, which showed that the drug has a good affinity with the polymer (χ = 0.489) according to Flory-Huggins theory and that lyoprotectants reduced the crystallinity of PEG in mPEG2k-b-PLA2.4k and played a space-protective role in the lyophilization process. In vivo experiments showed that micellization could improve the drug bioavailability and give a high therapeutic effect with a tumor inhibition rate of 84.5% under the tolerated dose.

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Funding

This work was supported by the National Mega-Project for Innovative Drugs [grant number 2019ZX09721001], Liaoning Revitalization Talents Program [grant number XLYC1908031], and the Project of Liaoning Provincial Department of Education [grant number 2019LQN07].

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, China

    Ying Zhang, Yi Liu, Na Wang, Hongbing Liu, Jingxin Gou, Haibing He, Yu Zhang, Tian Yin, Yanjiao Wang & Xing Tang

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  1. Ying Zhang
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  2. Yi Liu
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  3. Na Wang
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  4. Hongbing Liu
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  7. Yu Zhang
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  10. Xing Tang
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Correspondence to Xing Tang.

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All animal experiments were conducted according to the Guiding Principles in Shenyang Pharmaceutical University. The experiments were approved by the ethical committee of Shenyang Pharmaceutical University.

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Zhang, Y., Liu, Y., Wang, N. et al. Preparation of mPEG-b-PLA/TM-2 Micelle Lyophilized Products by Mixed Lyoprotectors and Antitumor Effect In Vivo. AAPS PharmSciTech 22, 38 (2021). https://doi.org/10.1208/s12249-020-01885-9

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