Supervisor: Prof. Caterina Cristallini - Prof. Maria Grazia Cascone

Title: Development of new intelligent nano-systems for the treatment of cardiovascular diseases and cancer

Abstract:
Cardiac disease and cancer are the main causes of mortality in the western world.
The traditional treatment foresees the administration of high doses of active principle which is unable to reach the target tissue in a selective way without causing side effects. Moreover high concentrations are not reached in the target tissues.
In this sense the creation of intelligent polymeric nanosystems is particularly promising because they are able to release the drug in a specific, controlled and quantitative way.
Nanosystems can be designed so as to a) encapsulate a high quantity of drug, b) functionalized by ligands with high specificity and affinity towards the target tissue, c) contain different types of drugs for treatment requiring combined action, d) cross biological barriers in different way from traditional drugs.
The main aim of this research project is concerned with the design and creation of new nanoparticles using multifunctional polymeric materials for the release of bioactive agents toward a specific pathological area of the body.
The ability to load modified nanoparticles on polymeric scaffolds for in situ release of active principles which can promote the regeneration of the tissue will be also evaluated.
Growth factors and gene specific oligonucleotidic drugs (DNA, RNA, ribozymes) which can guide the regeneration of cardiovascular tissue or selectively inhibit the expression of crucial genes in tumoral tissues will be considered.
Project will be structured in the following phases:
• Synthesis and characterization of the nanoparticles obtained by the copolymerization of monomers selected on the bases of chemical and physical characteristics of the active principle to be included. The most suitable method of production will be defined.
• Preparation of intelligent nanoparticles in nano-capsular form so as to obtain an internal reserve with a high content of the active principle. Innovative functionalization techniques will be used to maximise the ability of the nanocarriers to penetrate biological barriers and favour the internalization in the specific cells. These results will be obtained by controlling their shape and size during polymerization, by decorating their surface with molecules and introducing specific sites using Molecular Imprinting technique.
• Preparation and characterization of hollow fibre scaffolds modified with intelligent nanoparticles. Hydrogel structures made of biological and/or synthetic polymers will be designed in the form of hollow fibres using dry-wet spinning techniques. Suitable deposition processes will be identified to incorporate the nanocarriers on the scaffolds surface.

Morphological, physico-chemical, functional, mechanical and biological characterizations of nanocarriers and integrated scaffolds/nanocarriers systems will be carried out using SEM, light scattering, HPLC, FT-IR Chemical Imaging analysis, DMA analysis and cell culture methods.