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    Enhancing Docetaxel Delivery to Multidrug-Resistant Cancer Cells with Albumin-Coated Nanocrystals
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    • Sheryhan F. Gad
      Sheryhan F. Gad
      Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
      Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States
      More by Sheryhan F. Gad
    • Joonyoung Park
      Joonyoung Park
      Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States
      More by Joonyoung Park
    • Ji Eun Park
      Ji Eun Park
      College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
      More by Ji Eun Park
    • Gihan N. Fetih
      Gihan N. Fetih
      Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
      More by Gihan N. Fetih
    • Sozan S. Tous
      Sozan S. Tous
      Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
      More by Sozan S. Tous
    • Wooin Lee
      Wooin Lee
      College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
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    • Yoon Yeo*
      Yoon Yeo
      Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States
      Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States
      *Phone: 765.496.9608. Fax: 765.494.6545. E-mail: [email protected]
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      Orcidhttp://orcid.org/0000-0001-9505-7701
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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2018, 15, 3, 871–881
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    https://doi.org/10.1021/acs.molpharmaceut.7b00783
    Published January 17, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel (DTX) is challenging due to the low bioavailability and the toxicity related to solubilizing excipients. Colloidal nanoparticles are used as alternative carriers, but low drug loading capacity and circulation instability limit their clinical translation. To address these challenges, DTX nanocrystals (NCs) were prepared using Pluronic F127 as an intermediate stabilizer and albumin as a functional surface modifier, which were previously found to be effective in producing small and stable NCs. We hypothesize that the albumin-coated DTX NCs (DTX-F-alb) will remain stable in serum-containing medium so as to effectively leverage the enhanced permeability and retention effect. In addition, the surface-bound albumin, in its native form, may contribute to cellular transport of NCs through interactions with albumin-binding proteins such as secreted protein acidic and rich in cysteine (SPARC). DTX-F-alb NCs showed sheet-like structure with an average length, width, and thickness of 284 ± 96, 173 ± 56, and 40 ± 8 nm and remained stable in 50% serum solution at a concentration greater than 10 μg/mL. Cytotoxicity and cellular uptake of DTX-F-alb and unformulated (free) DTX were compared on three cell lines with different levels of SPARC expression and DTX sensitivity. While the uptake of free DTX was highly dependent on DTX sensitivity, DTX-F-alb treatment resulted in relatively consistent cellular levels of DTX. Free DTX was more efficient in entering drug-sensitive B16F10 and SKOV-3 cells than DTX-F-alb, with consistent cytotoxic effects. In contrast, multidrug-resistant NCI/ADR-RES cells took up DTX-F-alb more than free DTX with time and responded better to the former. This difference was reduced by SPARC knockdown. The high SPARC expression level of NCI/ADR-RES cells, the known affinity of albumin for SPARC, and the opposing effect of SPARC knockdown support that DTX-F-alb have exploited the surface-bound albumin-SPARC interaction in entering NCI/ADR-RES cells. Albumin-coated NC system is a promising formulation for the delivery of hydrophobic anticancer drugs to multidrug-resistant tumors.

    Copyright © 2018 American Chemical Society

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.molpharmaceut.7b00783.

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    This article is cited by 28 publications.

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    24. Jianzhu Wang, Yu Ding, Wei Zhou. Albumin self-modified liposomes for hepatic fibrosis therapy via SPARC-dependent pathways. International Journal of Pharmaceutics 2020, 574 , 118940. https://doi.org/10.1016/j.ijpharm.2019.118940
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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2018, 15, 3, 871–881
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.molpharmaceut.7b00783
    Published January 17, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

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