Speaker
Description
The era of Covid-19 reminds us how difficult it is to treat patients with acute respiratory distress syndrome (ARDS) therefore monitoring of the spatial distribution of the directly administrated drug to the lungs is very demanded.
In this work, we focused on the synthesis, functionalization of magnetic nanoparticles, N-acetylcysteine conjugation to magnetic nanoparticles and the study of drug distribution in the lungs in the aforementioned ARDS by magnetic resonance imaging (MRI). N-acetylcysteine (ACC) is a mucolytic drug commonly used in the treatment of the respiratory tract. The drug dissolves all the components that cause mucus to become viscous and thus promotes expectoration. The first step was the preparation of a conjugate consisting of magnetic nanoparticles modified with amino functional groups suitable for drug conjugation. Nanoparticle functionalization and drug conjugation were optimized and studied by different physicochemical methods such as SEM and TEM, Dynamic Light Scattering (DLS), Electrophoretic Light Scattering, UV/VIS spectroscopy, or magnetic measurements to obtain information about morphology, size distribution, surface charge, drug and magnetite concentrations and, last but not least, information about magnetic properties.
We managed to prepare conjugate with the optimal ACC loading concentration of $1.2$ mg/ml which corresponds to ACC/MNPs w/w ratio = $5$. Before the study of drug distribution in the lungs using MRI, unconjugated amino functionalized MNPs were first characterized by MRI relaxometry in order to determine MRI relaxation properties in vitro and simultaneously to reveal the spatial distribution of MNPs in the lungs ex vivo. We found prevailing $T_2$ relaxation with high transverse relaxivity values ($r_2 = 509.14$ $\pm$ $15.27$ mM$^{-1}$s$^{-1}$, $r_2^* = 663.58$ $\pm$ $19.91$ mM$^{-1}$s$^{-1}$), which allowed contrast imaging and spatial distribution determination of MNPs in lungs ex vivo.
Acknowledgements
The work was supported by the Slovak Research and Development Agency under contract APVV-DS-FR-22-0037, and by the Slovak Science Grant Agency VEGA - Project No. 2/0049/23.
