Part of the work of the project focuses on the "Design, Synthesis and Characterization of new CD derivatives; establishment of sustainable preparation protocols; development of delivery and sensor systems". The first results are contained in a report with new sustainable Routes of Synthesis and 2 protocols are particularly relevant:
a) 1 viable protocol for the regioselective allylation of CD monomers and dimers and 1 for the regioselective installation of alkylamine groups onto CD monomers and dimers;
b) 1 sustainable protocol for the synthesis and characterization of esters cross-linked CD polymers.
We have also optimized protocols for the synthesis of citric acid-crosslinked polymers. Specifically, we focused on cysteamine-modified β- and γ-cyclodextrins (cyst-β/γCDs) and investigated their polymerization with citric acid, 3,3′-dithiodipropionic acid, and toluene diisocyanate.
We also obtained the first set of results on CD hydrogels. Specifically, the design and synthesis of biocompatible and biodegradable hydrogel matrices focused on developing crosslinked pullulan-based hydrogels, leveraging pullulan’s biocompatibility, sustainability, and water solubility to create versatile materials for sensor applications.
Another part of the project work deals with (i) the rationalisation of molecular mechanisms underlying interaction of CDs with different cell types, and (ii) the assessment of the biological activity of new CD-based APIs and multicargo delivery systems in 2D and 3D models. The main achievements concern nucleic acid delivery, a very challenging goal, with potential applications in different fields going from cancer treatment to vaccine development: in aqueous environments, innovative βCD with cationic centers and hydrophobic tails self-assembly into bilayer vesicles, with their stability influenced by pH. They are able to co-assembly with plasmid DNA (pDNA), leading to the formation of DNA formulations upon a simple mixing process. Different short CD polymers were tested as delivery tool for nucleic acid molecular beacons and the first results on their intrinsic toxicity were obtained. The less toxic ones displayed transfection efficiency for the selected molecular beacon that was comparable with transfectamine protocols.
Finally, Folate-modified CDs functionalizing the primary face with aliphatic chains were obtained that self-assembly into small nanoparticles. Insight were obtained for these nanoparticles undergoing folate receptor-mediated endocytosis in selected cancer cell lines.
