Strategies for functionalization of magnetic nanoparticles for oral delivery evaluated by biomagnetic techniques

• Grant number: 23/18170-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Biophysics - Biophysics of Processes and Systems
• Principal Investigator: José Ricardo de Arruda Miranda
• Grantee: Raffael Greggio Willmann
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 18/16939-8 - Development and implementation of novel acoustic, magnetic and optical techniques for diagnostic and therapeutic applications, AP.TEM

Abstract

In recent years, nanotechnology has emerged as a potential tool to overcome barriers to drug delivery in the treatment of pathologies such as cancer. To overcome these barriers, nanotechnology uses nanostructured systems, called nanoparticles, which consist of a coated core. Among the nanoparticles that show high potential are magnetic nanoparticles (MNPs), which fall into a class of nanoparticles with theranostic characteristics, that is, they have functionality to act as tracers in diagnostic techniques, such as magnetic resonance imaging, or to act in the treatment of pathologies, acting as guided drug carriers. In this context, these nanostructured systems present high clinical potential, promoting the possibility of acting as a component of pathologies such as cancer. Currently, one of the main barriers to be overcome for drug delivery through MNPs is the route of administration, which currently only presents bioavailability when administered intravenously, which is not interesting for patient self-administration. However, recent studies show that the surface charge (zeta potential) of the MNPs confers better cellular internalization to these systems. Thus, the project aims to study the absorption of magnetic nanoparticles with positive surface charge through oral administration, studying the biodistribution of MNPs after administration in organs of interest such as the liver and spleen. For the analysis of biodistribution in the organs of interest, the techniques of Alternating Current Biosusceptometry (ACB) and Electron Paramagnetic Resonance (EPR) will be used in a complementary way. These techniques have the ability to quantify magnetic materials in tissues, thus, the study of the absorption of MNPs becomes viable by the possibility of analyzing tissues individually and opens the possibility of confirming their absorption if after oral administration a magnetic signal is found in tissue such as blood, liver and spleen. For this, magnetic nanoparticles coated with casein, positive Polyethylene glycol (PEG) and cysteine will be synthesized, which make the surface charge of the MNPs positive, after that, they will be administered by gavage in Wistar line rats. With the anesthetized rats, they will be decapitated and the collection of organs for biodistribution analysis by the aforementioned techniques will be made. This project has the potential to contribute substantially to the understanding of nanoparticle absorption by the GIT, providing information that will contribute to the construction of the area of nanomedicine and development of the area.