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Galactose-Containing Polymer-DOX Conjugates for Targeting Drug Delivery

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Abstract

A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl-D-galactopyranose) (mPEG-b-PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG-b-PMAGP-co-DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive. The cellular uptake behavior of free-DOX and mPEG-b-PMAGP-co-DOX nanoparticles by asialoglycoprotein (ASGP) receptor-positive cancer cell line (HepG2) and ASGP receptor-negative cancer cell lines (MCF-7 and A549 cells) was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM), respectively. The mPEG-b-PMAGP-co-DOX nanoparticles which contain galactose functional groups exhibited higher cellular uptake behavior via ASGP receptor-mediated endocytosis in HepG2 cells than in other two cancer cells. The in vitro cytotoxicity assay manifested that the mPEG-b-PMAGP-co-DOX nanoparticles exhibited higher anticancer efficacy against HepG2 cells than MCF-7 cells. These results indicated that the multifunctional mPEG-b-PMAGP-co-DOX nanoparticles possessing pH-responsible and hepatoma-targeting function have great potential to be used as a targeting drug delivery system for hepatoma therapy.

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Acknowledgments

This work was financially supported by Shandong Provincial Natural Science Foundation, China (ZR2014HM096, ZR2013EMQ008, ZR2015HL123); Project of Medical and Health Science and Technology Development Program in Shandong Province (2014WS0484); and Science and Technology Plan Project of colleges and universities in Shandong Province (J14LM51).

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    Authors and Affiliations

    1. School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People’s Republic of China

      Yujie Sun, Jing Zhang, Baocheng Tian, Yanan Shi, Yuanyuan Ding, Lele Wang & Jingtian Han

    2. Merial New Zealand, 14 Blackburn Road, Auckland, New Zealand

      Jian Han

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    1. Yujie Sun
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    2. Jing Zhang
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    Correspondence to Jingtian Han.

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    Yujie Sun and Jing Zhang are co-first authors.

    Yujie Sun and Jing Zhang contributed equally to this work.

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    Sun, Y., Zhang, J., Han, J. et al. Galactose-Containing Polymer-DOX Conjugates for Targeting Drug Delivery. AAPS PharmSciTech 18, 749–758 (2017). https://doi.org/10.1208/s12249-016-0557-4

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    • DOI: https://doi.org/10.1208/s12249-016-0557-4

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