International Journal of Nanomedicine (Feb 2019)
Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
Abstract
Esma Alp,1–4 Fehmi Damkaci,2 Eylem Guven,1 Martin Tenniswood3,4 1Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, Ankara 06800, Turkey; 2Department of Chemistry, State University of New York at Oswego, Oswego, NY 13126, USA; 3Cancer Research Center, Rensselaer, NY 12144, USA; 4Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, NY 12144, USA Background: The efficacy of epigenetic drugs, such as histone deacetylase inhibitors, is often diminished by poor aqueous solubility resulting in limited bioavailability and a low therapeutic index. To overcome the suboptimal therapeutic index, we have developed a biocompatible starch nanoparticle formulation of CG-1521, a histone deacetylase inhibitor in preclinical development for hard-to-treat breast cancers, which improves its bioavailability and half-life. Methods: The physicochemical parameters (size, zeta potential, morphology, loading, and release kinetics) of these nanoparticles (CG-NPs) have been optimized and their cytotoxic and apoptotic capacities measured in MCF-7 breast cancer cell line. The mechanism of action of the encapsulated drug was compared with the free drug at molecular level. Results: We show that encapsulation of CG-1521 substantially reduces the release rate of drug and provides a significantly enhanced cytotoxic ability of nanoparticles compared with equivalent dose of free CG-1521. CG-NPs induced cell cycle arrest and significant apoptosis in MCF-7 cells in vitro. The biological action of encapsulated drug has the similar impact with free drug on gene expression.Conclusion: The findings suggest that encapsulation of CG-1521 into starch nanoparticles can improve drug delivery of histone deacetylase inhibitors for breast cancer therapy without interfering with the mechanism of action of the drug. Keywords: cell cycle, apoptosis, DNA fragmentation, gene expression, epigenetics, MCF-7
