Chitosan based sorafenib tosylate loaded magnetic nanoparticles: Formulation and in-vitro characterization

Abstract

Biocompatible magnetic nanoparticles are used for various biomedical applications. This study reported the development of nanoparticles with magnetic properties by embedding magnetite particles in the drug-loaded, crosslinked matrix of chitosan. Sorafenib tosylate-loaded magnetic nanoparticles were prepared by a modified ionic-gelation method. Particle size, zeta potential, polydispersity index, and entrapment efficiency of nanoparticles were in the range of 95.6 ± 3.4 nm to 440.9 ± 7.3 nm, 12.8 ± 0.8 mV to 27.3 ± 1.1 mV, 0.289 ± 0.011 to 0.571 ± 0.011, and 54.36 ± 1.26 % to 79.67 ± 1.40 %, respectively. The XRD spectrum of formulation CMP-5 confirmed the amorphous nature of the loaded drug in nanoparticles. TEM image confirmed the spherical shape of nanoparticles. Atomic force microscopic image of formulation CMP-5 indicated a mean surface roughness of 10.3597 nm. The magnetization saturation of formulation CMP-5 was 24.74 emu/g. Electron paramagnetic resonance spectroscopy revealed that formulation CMP-5's g-Lande's factor was 4.27, which was extremely near to the 4.30 (usual for Fe³⁺ ions). Residual paramagnetic Fe³⁺ ions may be responsible for paramagnetic origin. The data suggests superparamagnetic nature of particles. Formulations released 28.66 ± 1.22 % to 53.24 ± 1.95 % and 70.13 ± 1.72 % to 92.48 ± 1.32 % of the loaded drug after 24 h in pH 6.8 and pH 1.2, respectively. The IC₅₀ value of formulation CMP-5 was 54.75 μg/mL in HepG2 (human hepatocellular carcinoma cell lines).

Keywords: Chitosan nanoparticle; Cytotoxicity; Ionic-gelation; MTT assay; Magnetic nanoparticle; Sorafenib.