2. Academic Validation
  3. PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3

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

  • Cancer Chemother Pharmacol. 2015 Oct;76(4):821-7. doi: 10.1007/s00280-015-2851-3.
Guus Martinus Bol 1 2,  Raheela Khan 1,  Marise Rosa Heerma van Voss 1 2,  Saritha Tantravedi 1,  Dorian Korz 1,  Yoshinori Kato 3 4 5,  Venu Raman 6 7 8
Affiliations

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.
  • 2 Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA, Utrecht, The Netherlands.
  • 3 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. ykato@mri.jhu.edu.
  • 4 Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ykato@mri.jhu.edu.
  • 5 Life Science Tokyo Advanced Research Center (L-StaR), Hoshi University School of Pharmacy and Pharmaceutical Science, Shinagawa-ku, Tokyo, Japan. ykato@mri.jhu.edu.
  • 6 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. vraman2@jhmi.edu.
  • 7 Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA, Utrecht, The Netherlands. vraman2@jhmi.edu.
  • 8 Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. vraman2@jhmi.edu.
PMID: 26330329 DOI: 10.1007/s00280-015-2851-3
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.

Keywords

DDX3; Drug release; Nanoparticles; PLGA; RK-33.

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