Monitoring of biodistribution of peptide-based drug delivery system by MRI
The main task of a modern colloidal delivery system is the programmed and targeted transport of a drug molecule. In the case of tuberculosis this aspect is highly important because the causative agent can hide and survive in the infected host and in this dormant, intracellular stage bacteria are extremely resistant to current therapy. In our previous work a new lipo-tuftsin based delivery system was developed and successfully employed to enhance the intracellular activity of antitubercular drugs. These conjugates were encapsulated with high efficiency into colloidal nanoparticles and tested in vivo in an animal model of tuberculosis. Present work aims to study the biodistribution of these colloidal constructs with state-of-the-art MRI imaging methods.
The nanoScan PET/MRI in the SE Nanobiotech and In Vivo Imaging Centre is a revolutionary multimodality imager providing advanced tool for PET researchers, utilizing the world′s best resolution PET module combined with a compact MRI system. The compact shielded MRI platform provides high spatial resolution of down to 100 µm, with superb soft tissue contrast required for anatomical/morphological imaging. It is optimized to perform fast, high-throughput imaging of a variety of applications and preclinical studies.
In the MTA-ELTE Research Group of Peptide Chemistry peptide-conjugates containing MRI contrast agent are synthesized and characterized. Lipo-peptide conjugates, which were effective in an in vivo tuberculosis challenge (Horváti, K et al. Tuberculosis 2015; Horváti, K et al. Bioconjug. Chem. 2014), will be modified with complexed gadolinium. The position of the contrast agent will be the same as the position of the drug molecule in our previous experiments.
The encapsulation of the gadolinium containing lipo-peptide conjugate will be performed in the Laboratory of Interfaces and Nanostructures, Institute of Chemistry, Eötvös Loránd University. Polimer-based delivery systems, such as PLA polyesters, PLG polyglycolyc acids and their copolymers, shows excellent biocompatibility and biodegradation. The peptide-conjugate content of the nanoparticles will be determined spectrophotometrically and/or by amino acid analysis. The size and morphology of the particles will be characterized by dynamic light scattering (DLS). Polydispersity and size distribution will be measured by using scanning electron microscopy (SEM).
Beside PLGA nanoparticles, three-component liposomal system will be also employed for encapsulation at the Department of Biophysics and Radiation Biology, Semmelweis University. These three-component liposomes keep in almost the same size distribution for as long as 4-6 weeks and can be utilized for macrophage drug-targeting. The gadolinium containing peptide-conjugate will be encapsulated into the three-component liposomes and the biodistribution will be compared to the PLGA nanoparticles and free peptide-conjugates.
Kata Horváti - Krisztina Szigeti - Éva Kiss - István Voszka