PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3.
Cancer Chemother Pharmacol
; 76(4): 821-7, 2015 Oct.
Article
in En
| MEDLINE
| ID: mdl-26330329
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polyglycolic Acid
/
Azepines
/
Drug Carriers
/
Drugs, Investigational
/
Lactic Acid
/
RNA Helicases
/
Enzyme Inhibitors
/
Nanoparticles
/
Imidazoles
/
Antineoplastic Agents
Language:
En
Journal:
Cancer Chemother Pharmacol
Year:
2015
Document type:
Article
Affiliation country:
United States