Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy

Disulfiram(DSF) showed great potential in an in vitro tumor therapy study; however, those results could not be applied to an in vivo study due to the extreme instability of DSF in blood. Here, we describe a system of methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)/poly(epsilon-caprolactone) (mPEG-PLGA/PCL) mixed nanoparticles (NPs) for DSF loading and delivery. By adjusting the mPEG-PLGA/PCL content ratios, the DSF loading capacity increased to 7.8%, while the hydrodynamic radii of the NPs were around 50-100 nm. The DSF-loaded NPs showed high stability in distilled water and 10% serum-containing phosphate buffered saline. The NPs efficiently protected DSF from degradation while maintaining its anti-tumor properties. Furthermore, a pharmacokinetics study demonstrated that NP delivery system enhanced the DSF concentration in the blood after tail vein injection. Finally, DSF delivery using this model effectively slowed the growth of a 4T1 murine xenograft tumor. From the Clinical Editor: The anti-tumor efficacy of the anti-alcoholic drug disulfiram has been known for some time. However, its use in the clinical setting is limited due to the underlying instability of the drug. In this study, the authors utilized a nanocarrier system of mPEGPLGA/PCL for the delivery of this drug. The promising results may allow encapsulation of other drugs. (c) 2015 Published by Elsevier Inc.