This study developed, for the first time, the N-2-hydroxypropyltimehyl ammonium chloride chitosan (N-2-HACC)/carboxymethyl chitosan (CMC) complex nanoparticles as a delivery carrier for the Newcastle disease virus (NDV). Nanoparticles were developed by complexation between the positively charged N-2-HACC and negatively charged CMC without using any crosslinkers. The structure and properties of these synthesized derivatives were characterized by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (H-1 NMR) spectroscopy, and X-ray diffraction (XRD) technologies. The antimicrobial activity of N-2-HACC against a Gram-positive bacteria (Staphylococcus aureus), four Gram-negative bacteria (Escherichia coli, Enterobacter aerogenes, Pseudomonas aeruginosa, and Enterobacter cloacae), and a fungus (Candida albicans), and its cytotoxicity were characterized in order to facilitate its use as a novel material for biomedical applications. The results indicated that the N-2-HACC had been prepared successfully and showed high antimicrobial activity against the tested bacteria and fungus, very low toxicity, and a high safety level. The water solubility and degree of substitution (DS) of the chitosan derivatives were also analyzed, and the effects of solution concentration on the mean diameter Polydispersity (PDI) and the Zeta potential of the blank nanoparticles were discussed. Tests of the N-2-HACC/CMC complex nanoparticles as a carrier for NDV revealed stable and long lasting release of the antigen. The western blotting analysis showed that NDV structural proteins were detected in the NDV-N-2-HACC/CMC-NPs. NDV was found to be released in the virus release assay of NDV-N-2-HACC/CMC-NPs. Based on these results, the N-2-HACC and CMC will be a new drug release carrier with great application potential. (C) 2013 Elsevier B.V. All rights reserved.