L'insegnamento prevede 3.0 CFU erogati con Didattica Innovativa come segue:
Blended Learning & Flipped Classroom
Corso di Studi
Codice Piano di Studio preventivamente approvato
Ing Ind - Inf (1 liv.)(ord. 270) - MI (347) INGEGNERIA CHIMICA
096205 - BIOMEDICAL PHYSICAL CHEMISTRY
055584 - BIOMEDICAL PHYSICAL CHEMISTRY
Ing Ind - Inf (Mag.)(ord. 270) - MI (471) BIOMEDICAL ENGINEERING - INGEGNERIA BIOMEDICA
055584 - BIOMEDICAL PHYSICAL CHEMISTRY
Ing Ind - Inf (Mag.)(ord. 270) - MI (472) CHEMICAL ENGINEERING - INGEGNERIA CHIMICA
055584 - BIOMEDICAL PHYSICAL CHEMISTRY
The goal of the course is to provide the engineering foundations and discuss the technological challenges related the the development of new therapeutic treatments.
In particular, the course addresses two main therapeutic approaches: therapeutic proteins and drug delivery.
The first one refers to the production of therapeutic proteins, such as monoclonal antibodies, fusion proteins, peptides and oligonucleotides, which are widely involved in the therapeutic treatment of various deases, for example in the areas of oncology, autoimmune response and disorders of the the central nervous system. The basic concepts which drive the realization of an industrial unit for the production of therapeutic proteins under GMP conditions are discussed. These are discussed in connection with the various phases which lead to the introduction of a new drug in the market: the early stage of the process design and development, the production of small amounts of the drug needed for the clinical trials, and eventually the large commercial scale units for the production of the drugs for the patients. The analysis starts from the fedbatch and perfusion bioreactors for the production of the target protein through the recombanint technology using mammalian cells. Next the purification and virus inactivation processes are considered. Specific reference is made to chromatographic units, based on affinity, reverse phase and ion exchange, used at various levels of the production processes, invoving both the capture and the polishing steps. Particular attention is devoted to the emerging area of intensified production processes through continuous operation. This part of the course is treated mainly in the frontal lectures and in some of the research projects.
The second part refers to drug delivery processes, which aim at delivering the drug at the specific location where it is needed, such as the cancer cell in the case of oncological therapies. The objective is to prevent or at least moderate the side effects related to systemic delivery, as it is the case for cancer chemiotherapies. The fundamental principle of the design of a drug delivery carrier is discussed and various options are discussed in connection to different administration processes. Next, the treatment focuses on the use of polymer nanoparticles to be used for the delivery of various drugs, including the case of gene therapies, as well as for diagnostic applications, such as imaging through different physical properties. The synthesis of various nanoparticles, with different size and surface properties (e.g., charge and chemical functionalities), and their efficiency in penetrating the target tissue are discussed. In this section, the treatment is mainly based on direct laboratory activities and frontal lectures. In particular, after some introductory lectures about the relevant chemical aspects, the students are asked to enter the laboratory and actually synthesize the designed polymer nanoparticles for the delivery of drugs for specific therapeutic indications.
Risultati di apprendimento attesi
The lectures will allow the students to:
- understand the issues (efficacy, safety and cost) related to the use of proteins for therapeutic applications
- become familiar with current processes and future needs for the GMP manufacturing of therapeutic proteins
- design the various process steps: bioreactor, virus inactivation, capture and polishing
- understand and apply process intensification through the continuous operation of poduction industrial units
- understand the role of organic and inorganic nanoparticles in biomedical appliacations
- understand the polymer reaction and colloidal engineering aspects related to the use of nanoparticles in medicine
- design and synthesize polymers and polymer nanoparticles for therapeutic and diagnostic applications
The laboratory projects will allow students to:
- design and synthesize in a chemical laboratory drug carriers based on polymers and polymer nanoparticles for specific therapeutic indications.
The research projects will allow the students to:
- design, based on literature information and, if needed, some experimental activity in silico or in wet laboratories, the necessary steps for solving a specific research problem, related to some of the topics treated in the lectures. This may refer to a polymer device for a specific therapeutic treatment or the production of a spectific biopharmaceutical format, like a bispecific antibody or a conjugated therapeutic protein. The students work autonomously, over a period of time spread during the entire semester, with the course assistants providing consulting and coaching support.
The lectures describe the physicochemical fundamentals of processes for the production of drugs and devices for biomedical applications.
In the first part we refer to the manufacturing of therapeutic proteins, such as monoclonal antibodies, through recombinant technology. These are typically expressed in mammalian cell cultures and subsequently purified through various steps, referred to as capture and polishing, usually based on chromatographic techniques. The relevant engineering aspects of these processes are discussed 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 charge variant distributions and glycosylation patterns. The relation between the process operating conditions and the drug efficacy and safety for the patient are discussed, also in connection with economical factors.
The second part refers to the synthesis of polymers and polymer nanoparticles for the delivery of active therapeutic principles. We begin from general considerations about different polymerization chemistries and processes, in order to provide the necessary background to all students. In particular we discuss: the kinetics of free radical polymerization, emulsion polymerization processes; living polymerization processes: ROP, RAFT and ATRP and finally methods for the synthesis of polymeric nanoparticles. Colloidal stability is discussed with reference to the shelf drug stability and its formulation depending on the type of drug administration.
Laboratory Project (Laboratorio Sperimentale)
After the introductory lectures, the students move to the polymer laboratory where they are divided in groups of 3/4 members and conduct selected experiments for the synthesis of polymer nanoparticles and gels for localized and controlled drug delivery.
In particular, the topics covered in the laboratory experiences include:
Living polymerizations: ROP and RAFT
RAFT Emulsion polymerization
Synthesis of polymer nanoparticles
Magnetic and fluorescent nanoparticles for medical imaging
Hydrophilic gels for localised delivery of antibiotics
Polymer nanoparticles for gene therapy
Eventually, a project report is prepared and submitted/presented.
Research Project (Laboratorio di Progetto)
The students divided in groups of 3/4 are given a project about the production of a polymer device in the area of drug delivery, tissue engineering or gel degradation for local and controlled release. Alternatively, the project may refer to the development from the clinical to the commercial scale of a biopharmaceutical. The project is developed according to the following steps:
- literature search
- definition of the project strategy
- definition and planning of the proect activity
- in silico or in wet laboratory activity
- delivery of the results: written report and oral presentation
Students are required to be familiar with basic principles of chemistry, biology and physical chemistry.
Modalità di valutazione
The final evaluation consists of three contributions: oral exam on the content of the lectures (60%), laboratory project written final report (20%) and research project written final report and oral presentation (20%).
In particular, in the oral examination, the student should demonstrate to have acquired the understanding and knowledge about the various aspects discussed in the lectures, about the processes for the production of therapeutic proteins. The principles of protein production, methods for protein purification with particular attention to chromatographic techniques constitute an important part of the exam. The oral exam accounts for 60% of the final grade.
The reports for each laboratory experiment will be evaluated and credits will be given based on the candidate understanding of the obtained results and of the related critical issues. This implies that unsuccesfull results are accepted provided that the candidate can explain them and indicate possible alternatives. Attendance to the laboratory experiments is required, in order to collect the data necessary for the final written report. The evaluation of the laboratory reports accounts for 20% of the final grade.
For the research projects, each work team is required to produce and discuss orally a report about the obtained results, in front of the class colleagues and the instructors. The students are required to have properly understood and master the research project they worked on, to critically analyze the obtained final results and to illustrate the required subsequent developments. The discussion of the results of the project accounts for 20% of the final grade.
M. Wolf, J.-M. Bielser and M. Morbidelli, Perfusion Cell Culture Processes for Biopharmaceuticals , Editore: Cambridge University Press, New York, Anno edizione: 2020
D. Pfister, L. Nicoud and M. Morbidelli, Continuous Biopharmaceutical Processes , Editore: Cambridge University Press, New York, Anno edizione: 2018
Massimo Morbidelli, Polymer Reaction and Colloidal Engineering Note:
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Tipo Forma Didattica
Ore di attività svolte in aula
Ore di studio autonome
Laboratorio Di Progetto
Informazioni in lingua inglese a supporto dell'internazionalizzazione
Insegnamento erogato in lingua
Disponibilità di materiale didattico/slides in lingua inglese
Disponibilità di libri di testo/bibliografia in lingua inglese
Possibilità di sostenere l'esame in lingua inglese
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