Comprehensive characterization and development of multi-core shell superparamagnetic nanoparticles for controlled delivery of drugs and their kinetic release modelling

Abstract

The nanoparticles designed for application in cancer treatment should have biocompatibility, colloidal stability and triggered release at tumor sites. Magnetic nanoparticles arise as an interesting option to be used as drug nanocarriers, considering the possibility of driving nanoparticles to the correct delivery site and exploring different triggers to achieve such accomplishment. In this study, nickel ferrite nanoparticles are explored as a magnetic core for drug delivery systems, using doxorubicin and omeprazole as model drugs. The developed nickel ferrite presents a strong superparamagnetic behavior and high purity, as demonstrated by magnetometry and TGA results. The carbon-coating procedure and functionalization allowed the nanoparticle to achieve the desired characteristics for biomedical applications (i.e. stability in water, biocompatibility, and size). According to TEM results, the final carbon-coated magnetic nanoparticles have an average size of 25.09 ± 0.58 nm and multi-core shell architecture, which is suitable for biomedical applications as drug nanocarriers. In addition, DLS demonstrated that functionalized nanoparticles are monodisperse, with a hydrodynamic diameter of 167 ± 59 nm, which fits the recommended range (100–200 nm) to benefit from enhanced permeability and retention effect. Drug loading tests with doxorubicin and omeprazole revealed the versatility of the designed nanoparticles, able to load 97% of doxorubicin and 51% of omeprazole. The pH-triggered release was also confirmed for both pharmacological compounds, showing a higher cumulative drug under acidic conditions (simulating a tumor microenvironment). Finally, the kinetic analysis applied to the study of the release mechanism of both medicines showed that non-linear models fit with higher accuracy the experimental data.