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PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Background

The DDX3 helicase inhibitor RK-33 is a newly developed anticancer agent that showed promising results in preclinical research (Bol et al. EMBO Mol Med, 7(5):648–649, 2015). However, due to the physicochemical and pharmacological characteristics of RK-33, we initiated development of alternative formulations of RK-33 by preparing sustained release nanoparticles that can be administered intravenously.

Methods

In this study, RK-33 was encapsulated in poly(lactic-co-glycolic acid) (PLGA), one of the most well-developed biodegradable polymers, using the emulsion solvent evaporation method.

Results

Hydrodynamic diameter of RK-33-PLGA nanoparticles was about 245 nm with a negative charge, and RK-33-PLGA nanoparticles had a payload of 1.4 % RK-33. RK-33 was released from the PLGA nanoparticles over 7 days (90 ± 5.7 % released by day 7) and exhibited cytotoxicity to human breast carcinoma MCF-7 cells in a time-dependent manner. Moreover, RK-33-PLGA nanoparticles were well tolerated, and systemic retention of RK-33 was markedly improved in normal mice.

Conclusions

PLGA nanoparticles have a potential as a parenteral formulation of RK-33.

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Author information

Author notes

  1. Yoshinori Kato

    Present address: Life Science Tokyo Advanced Research Center (L-StaR), Hoshi University School of Pharmacy and Pharmaceutical Science, Shinagawa-ku, Tokyo, Japan

Authors and Affiliations

  1. Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Traylor 340, Baltimore, MD, 21205, USA

    Guus Martinus Bol, Raheela Khan, Marise Rosa Heerma van Voss, Saritha Tantravedi, Dorian Korz, Yoshinori Kato & Venu Raman

  2. Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA, Utrecht, The Netherlands

    Guus Martinus Bol, Marise Rosa Heerma van Voss & Venu Raman

  3. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Yoshinori Kato & Venu Raman

Authors
  1. Guus Martinus Bol
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  2. Raheela Khan
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Corresponding authors

Correspondence to Yoshinori Kato or Venu Raman.

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Financial support

This work was supported by the Dr. Saal van Swanenberg foundation (G.B.), the Dutch cancer society (UU 2010-4856) (G.B.), DoD Idea Award (W81XWH-10-1-0603) (V.R.).

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There are no financial disclosures from any authors.

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Bol, G.M., Khan, R., Heerma van Voss, M.R. et al. PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3. Cancer Chemother Pharmacol 76, 821–827 (2015). https://doi.org/10.1007/s00280-015-2851-3

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  • DOI: https://doi.org/10.1007/s00280-015-2851-3

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