Comprehensive characterization and development of multi-core shell superparamagnetic nanoparticles for controlled delivery of drugs and their kinetic release modelling
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.
This work is a result of Project “RTChip4Theranostics – Real time Liver-on-a-chip platform with integrated micro(bio)sensors for preclinical validation of graphene-based magnetic nanocarriers towards cancer theranostics”, with the reference NORTE-01-0145-FEDER-029394, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); and CIMO (UIDB/00690/2020) through FEDER under Program PT2020. Financial support was also obtained from LA/P/0045/2020 (AliCE), UIDB/50020/2020 and UIDP/50020/2020 (LSRE-LCM), funded by national funds through FCT/MCTES (PIDDAC). Adriano S. Silva thanks his doctoral Grant with reference SFRH/BD/151346/2021 financed by the Portuguese Foundation for Science and Technology (FCT), with funds from NORTE2020, under the MIT Portugal Program. Fernanda F. Roman acknowledges FCT and FSE for the individual research grant (SFRH/BD/143224/2019). Jose L. Diaz De Tuesta acknowledges the financial support through the program of Atracción al Talento of Comunidad de Madrid (Spain) for the individual research grant 2022-T1/AMB-23946. Marta Pedrosa acknowledges FCT funding under the 5th Edition Call for Scientific Employment Stimulus – Individual Contract (2022.00192.CEECIND).
- Artículos de Revista