Radiation-engineered polymer nano-platforms for targeted drug delivery

Abstract

In the last twenty years, several nanobiomaterial-based nanocarriers, so-called nanoplatforms, have been proposed for the treatment of life- threating or quality-of-life-impairing diseases. The role of the nanocarrier is to increase drug localisation via passive and active targeting, to protect the drug from degradation and premature clearance, to facilitate its bypass through biological barriers and increase uptake by cells. For a successful translational research, the system composition should be as simple as possible, and the manufacturing processes should be fast, flexible and should enable a rapid product development from lab-scale to low cost, large-scale production. With this focus, we have developed a polymer-based nanoplatform, which adopts as a main manufacturing step an industry-standard EB sterilisation process (10 MeV, 10 kW linac accelerator at INCT, Poland; 300-400 Hz, 20 or 40 kGy per pass). Starting from aqueous solutions of poly(N-vinyl pyrrolidone), varying polymer concentration and absorbed dose, we have obtained a family of nanoscalar polymer networks, or nanogels, with various, controlled particle sizes.Reactive functional groups (carboxyl groups and amino groups) have been generated by irradiation, which contribute to the colloidal stability of the nanoparticles and can be used for covalent conjugation of antibodies and peptides to provide active targeting functions, and therapeutic moelcules. The properties of these nanoparticles as delivery nanodevices, from in-vitro and in vivo studies, will be here presented. Their prospects as nanocarriers for anticancer therapies or for brain targeted insulin delivery in the treatment of Alzheimer's disease will be also discussed.