The goal of the course is to provide the students with the the knowledge of the main products that are currently finding great interest in the biomedical field. In particular, the course is organized in two main sections. The former deals with the principles of colloidal chemistry and physics with main focus on the synthesis and adoption of inorganic and organic (i.e. polymeric) nanoparticles for drug delivery and imaging. This section is treated both theoretically and practically through laboratory experiences. In the second part of the course, the synthesis and purification of therapeutic proteins is covered.

The lectures will allow students to:

- know and discuss the role of organic and inorganic nanoparticles in the biomedical field

- know and discuss about the production of polymers and polymer nanoparticles for biomedical applications

- understand the radical chemistry and the conventional and controlled radical processes to produce polymers

- know and discuss about the manufacturing of therapeutic proteins

- know and discuss about the purification through continuous chromatography of therapeutic proteins

The laboratory will allow students to:

- synthesize in a chemical laboratory polymer devices for biomedical porpouses.

Lectures

This course describes the physicochemical aspects of two processes: the production of polymers and polymer nanoparticles for biomedical applications and the manufacturing and purification of therapeutic proteins.

Dealing with polymerization processes, the course starts from general considerations on different polymerization chemistries and the selection of the most suitable polymerization processes in the realization of biomedical devices. Then, the following aspects in the synthesis of polymers and polymer nanoparticles are reviewed: detailed kinetics of free radical polymerization; molecular weight distribution and chain composition control in copolymers; emulsion polymerization processes; synthetic methods for polymeric nanoparticles production; living polymerization processes: ROP, RAFT and ATRP.

Therapeutic proteins, such as monoclonal antibodies, are currently manufactured through recombinant technology. They are typically expressed in mammalian cell cultures and then purified through various steps, referred to as capture and polishing, usually based on chromatographic techniques. The relevant engineering aspects of this process are reviewed with a focus on productivity, yield and purity of the final product, but also on the quality of the final drug in terms of aggregates, fragments and distribution of variants in terms of differences in charge and in glycosylation pattern. These strongly affect the toxicity and efficacy of the final drug.

Laboratory

The students will be divided in work teams of 4 people and will experience, in a chemical laboratory, the following topics:

• Synthesis of fluorescent nanoparticles for optical imaging
• Synthesis of magnetic nanoparticles as contrast agents for magnetic resonance imaging
• Living polymerizations: ROP and RAFT
• RAFT Emulsion Polymerization in the synthesis of highly controllable colloids
• Synthesis of hydrophilic polymers and hydrogels

For each of the laboratory experience, a written report is required to the work teams.

Students are required to know the basic principles of physical chemistry.

The reports realized by the students for each laboratory experiences as well as the knowledge of the topics covered during the frontal lessons will be evaluated.

In particular, the attendance to the laboratory experiences is required to gather results and information necessary to the preparation of the report. A maximum of one absence is admitted. The laboratory reports should be delivered by the following laboratory experience. At the end of the course, the reports of the different experiences will be gathered and evaluated. A maximum grade of 27/30 can be reached with the reports. The students should demonstrate in the report: to master the subject of the experience, criticism in analysing the product they obtain and to make extensive reference to literature results on a similar topic.

The remaining points to reach 30/30 can be obtained in an oral examination where the student should demonstrate to have acquired the knowledge of the role of nanoparticles and therapeutic proteins in the biomedical field, the principles of radical chemistry and the controlled radical processes (including kinetic scheme, requisites and how the process can be conducted in different media), principles of protein production, methods for protein purification with particular attention to chromatographic techniques.