Public lecture by Professor Emeritus Costas Kiparissides

"Rational Design of Novel Drug Delivery Systems and Model-based Microbial Production of PHB in Alcaligenes latus Cultures" Public lecture by Professor Emeritus Costas Kiparissides, Energy Resources Institute, Centre for Research and Technology Hellas

Dr. Costas Kiparissides is an Emeritus Professor of Chemical Engineering at Aristotle University of Thessaloniki (AUTH) since 1981. He received his Diploma in Chemical Engineering from NTUA (1971) and his Ph.D. from McMaster University in Canada (1978). From 1978-1983, he taught as an Assistant and Associate Professor at the University of Alberta in Canada.

Prof. C. Kiparissides has been a Visiting Professor of Chemical Engineering at University of Newcastle in U.K. (1995-2002) and Queen’s University in Canada (1987-1989), the “Borealis” Chair Professor at PetroleumInstitute in United Arab Emirates (2013-2015). He has served as Director of the Chemical Process Engineering Research Institute-CPERI (2001-2006) and Director of the Centre for Research and Technology Hellas-CERTH (2005-2010).

He has served in numerous National, International and EU scientific-technical working committees on Science, Innovation and Technologies Policies. He has supervised more than fifty Ph.D. graduate students, 160 Diploma Theses and has presented more than three hundred invited seminars and lectures at international scientific conferences, industrial research centres, institutes and universities in Europe and North America. He has published over 220 scientific papers in refereed journals, 450 conference papers and 20 books and reports. His published work has received more than 5000 citations. He has been awarded more than 50 National, industrial and EU research grants of over 15 million Euros in total.

His current research interests are in the areas of advanced multi-scale modelling of chemical and biological systems, functional materials, and sustainable bioprocesses, nanotechnology applications in targeted delivery systems, nano-diagnostics and in virtual physiological human.

In the first part of the seminar, we will review recent experimental advances in the development of mucus penetrating nanocarriers for oral delivery of biopharmaceutics. In the second part of the lecture, we will highlight some experimental and multi-scale modeling aspects of microbial production of PHB in Alcaligenes latus Cultures. Both topics have been parts of two EU-funded collaborative projects. 

1. Rational Design of Mucus Permeating Nanocarriers for Oral Delivery of Biopharmaceutics Biologicals, including peptides/proteins and DNA/RNA-based drugs, have become the new, pioneering generation of therapeutics for the treatment of numerous diseases. However, their vast majority is administered via the less acceptable parenteral route, as the highly preferred oral administration route turns

out to be problematic due to numerous barriers being associated with the gastrointestinal tract (GIT) with concomitant their extremely low in vivo efficacy. To overcome the GIT barriers, and, thus, increase the in vivo bioavailability of biologicals, a great variety of strategies such as modification of drugs structure, coadministration of auxiliary agents (e.g., enzyme inhibitors, permeation enhancers) and development of different carrier systems have been proposed.To date various types of nanocarriers have been developed for the oral administration of biopharmaceutics. In this seminar, a “rational design” approach will be presented

to circumvent current limitations of nanocarrier-based drug delivery formulations. State-of-the-art mucus permeating nanocarriers (e.g., self-emulsifying drug delivery systems, polyelectrolyte complexes, anionic lipid emulsions, etc.) for controlled delivery of biomolecules will be presented and critically assessed. The nanocarriers were characterized with respect to physicochemical properties, protein loading and release, permeation through fresh porcine intestinal mucus and ability to protect drugs from enzymatic degradation. 

2. Multi-scale Modeling ofMicrobial PHB Production in Alcaligenes latus Cultures

Various bacterial species can accumulate intracellularly granules of Polyhydroxyalkanoates (PHAs), as energy and carbon reserves. The high production cost of PHAs as well as their efficient separation from the harvested cells and subsequent downstream processing are some of the problems that hinder their wide applicability. Therefore, there is a growing need for the development of optimal microbial processes in order to improve the overall process efficiency and reduce the total production cost. To this end, advanced mathematical models can provide the means to elucidate and control the underlying biochemical phenomena, leading to the production of biopolymers with desirable molecular and end-use properties, in a cost-effective way. In this seminar, an integrated metabolic/kinetic/macroscopic model will be presented for the dynamic simulation of the Poly(3-hydroxybutytrate) (PHB) production in A. latus cultures. The proposed approach includes a realistic description

of cells’ metabolism, accounting for the effects of the medium composition, culture aeration and operating policies (batch/fed-batch) on the PHB productivity and molecular properties. The model predicts the biomass

growth rate, the key nutrients assimilation rates, the oxygen transfer/uptake rates, the PHB production rate and its associated molecular weight distribution (MWD). Furthermore, a bivariate cell population balancemodel, accounting for cell division and partitioning of cellular material upon cell division, is employed to calculate the

dynamic evolution of cells population. A comprehensive experimental study was carried out to assess the effects of key-process variables on the PHB accumulation rate and itsMWD and the impact of various fed-batch policies on the PHB yield. Moreover, a comprehensive experimental analysis is carried out to assess the effects of the post-treatment conditions on the efficient polymer recovery and PHB MWD.