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

Cancer Chemotherapy and Pharmacology
Guus Martinus BolVenu Raman

Abstract

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

References

Sep 1, 1996·Journal of Pharmaceutical and Biomedical Analysis·R A CoeJ W Lee
Feb 27, 2004·Biochemical and Biophysical Research Communications·Jhy-Shrian HuangYuh-Shan Jou
Nov 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alan V BoddyA Hilary Calvert
Jan 1, 1985·Journal of Pharmaceutical and Biomedical Analysis·J den HartighH M Pinedo
Jul 17, 2008·Nucleic Acids Research·Chung-Sheng LeeRobin Reed
Oct 11, 2008·Cell Death and Differentiation·M SunR S Jope
Oct 28, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fabienne DanhierVéronique Préat
Nov 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shanta DharStephen J Lippard
Sep 29, 2009·Colloids and Surfaces. B, Biointerfaces·Avnesh KumariSubhash C Yadav
Aug 28, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fabienne DanhierVéronique Préat
Jan 18, 2011·Biochimica Et Biophysica Acta·Mianen SunRichard S Jope
May 17, 2011·ACS Medicinal Chemistry Letters·Atul KondaskarRamachandra S Hosmane
Dec 14, 2011·The New England Journal of Medicine·Lili WangCatherine J Wu
Feb 23, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fabienne DanhierVéronique Préat
Feb 16, 2013·Science·Cristina-Maria CruciatChristof Niehrs
Mar 31, 2015·EMBO Molecular Medicine·Guus M BolVenu Raman

❮ Previous
Next ❯

Citations

Apr 19, 2016·Pharmaceutical Patent Analyst·Hermann Am Mucke
Jan 27, 2017·Journal of the National Cancer Institute·Wanpei CaiAlan Prem Kumar
Dec 6, 2017·Biochemical and Biophysical Research Communications·Zhong WangQuan-Gen Gao
Apr 4, 2021·International Journal of Molecular Sciences·Olga Sergeeva, Timofei Zatsepin

❮ Previous
Next ❯

Related Concepts