Carboxymethylinulin-Chitosan Nanoparticles for the Delivery of Antineoplastic Mitoxantrone

ChemMedChem. 2016 Nov 7;11(21):2436-2444. doi: 10.1002/cmdc.201600385. Epub 2016 Oct 5.

Abstract

Mitoxantrone (MTX) is an antineoplastic agent whose use is limited by serious side effects on non-neoplastic cells. The aim of this study was the development of a new drug release system using an ionotropic gelation technique for microencapsulation of MTX in chitosan-carboxymethylinulin nanoparticles (CCInp), followed by evaluation of their cytotoxic effects on neoplastic MDA-MB-231 and non-neoplastic NIH3T3 cell lines. The CCInp were prepared through a new reliable method for easy functionalization of both inulin and chitosan. Both unloaded and drug-loaded nanoparticles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) and showed a spherical morphology with an average hydrodynamic diameter between 40 and 80 nm. Both nanoparticles were stable and easily degraded by lysozyme. MTX-loaded nanoparticles led to a greater mortality of MDA-MB-231 relative to free drug due to the ability of the nanoparticles to accumulate preferentially in neoplastic cells. The developed drug release system retains the ability to kill MDA-MB-231 cells in vitro, improving the survival of NIH3T3 cells.

Keywords: biopolymer; chitosan; ionotropic gelation; mitoxantrone; nanoparticles.