laboratory of polymer & biochemical engineering...

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BBiioocchheemmiiccaall EEnnggiinneeeerriinngg (LPBE )

Molecularly Imprinted PolymersMolecularly Imprinted Polymers

CharacterizationCharacterization

In vitro ModelsIn vitro Models

Targeted Delivery SystemsTargeted Delivery Systems

Modeling of Pulmonary & Nasal Modeling of Pulmonary & Nasal DeliveryDelivery

Biomimetic Biomimetic GelsGels

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The Laboratory of Polymer & Biochemical Engineering

The Laboratory of Polymer & Biochemical Engineering (LPBE) was established in 1985 within the Department of Chemical Engineering of Aristotle University of Thessaloniki (AUTh). The Laboratory is also associated with the Chemical Process Engineering Research Institute (CPERI) of the Center for Research and Technology Hellas (CERTH) a non-profit, research organization. The Laboratory's research activities fall into the following general areas:

Application of biosynthesis and biocatalysis for the production of novel, high-added value, functional biopolymers from renewable sources.

Development of functional micro-, nanoparticles and nanostructures for health, food and environmental applications.

Targeted delivery systems of proteinic/peptidic (P/P) drugs.

Cell transport studies. Mathematical modeling and experimental

investigation of polymer production processes. Design, computer control and optimization of

polymerization reactors. Molecular and morphological characterization of

polymers and biopolymers. LPBE is equipped with experimental facilities for the production of polymers, biopolymers and organic and hybrid micro- and nanoparticles and analytical equipment for their characterization. Presently, LPBE employs twelve doctoral research associates, eight Ph.D. candidates, three research associates and two technicians and over ten senior undergraduate students working on their Diploma Theses. Its present annual budget is about € 900,000. LPBE is supported to a large extent through research funds from the Greek Secretariat of Research and Technology, the European Commission, the Aristotle University of Thessaloniki, and major European Polymer Manufacturing Industries.

LPBE has a strong commitment to technology transfer to the international materials industry, with an emphasis on the development of innovative, tailor-made micro- and nano-carriers for drug delivery and biomedical applications, production of novel functional biopolymers and development of state-of-the-art software tools for computer-aided design, monitoring, optimization and control of a wide range of industrial polymerization processes.

Microencapsulation Techniques

Microencapsulation is a technology which comprises a number of physical and chemical methods aiming at wrapping small entities of

either hydrophilic or hydrophobic active ingredients (tiny solid particles, liquid droplets, or gas bubbles) in individual polymeric microcapsules or/and microparticles. The protective coating (i.e., wall material) generally consists of natural or synthetic polymers. Depending on the type of the encapsulated material and the ultimate product use, the size of the polymer microcapsules can range from a few nanometers to several millimeters. Control of the microcapsule / microparticle membrane thickness and its morphological properties as well as control of the capsule size and its distribution are the main requirements for the selection of an encapsulation method. The wall material is selected according to the physical properties of the core and the intended application.

Microcapsules/microparticles can be either in the form of reservoirs in which the active ingredient is surrounded by a suitable confinement material, or they can consist of a polymer matrix in which the active ingredient is dispersed. The confinement material in both systems serves as a barrier to the active agent which is released either by diffusion through the pores of the confinement material via the degradation of the polymer.

LPBE’s research activities include experimental investigations of the production of various types of microcapsules and microparticles by employing a number of physicochemical and physico-mechanical encapsulation methods and a great variety of polymeric wall materials as well as combination of the above methods for the production of composite microcapsules and microparticles with desired properties.

Drug loaded ethylcellulose & HPMA microparticles

Physicochemical Techniques ♦ Phase Separation / Coacervation ♦ Interfacial Polymerization ♦ Interfacial Deposition ♦ In Situ Polymerization ♦ Solvent Evaporation from Emulsions ♦ Suspension Cross-linking / Hydrogel Formation ♦ Suspension Congealing ♦ Solution Cross-linking ♦ Polymerization Techniques (e.g., precipitation

microsuspension, inverse suspension)

Physicomechanical Techniques ♦ Spray Dryer ♦ Spray Congealing ♦ Fluidized Bed

Nanocarriers for Targeted Delivery

Vaccination is the most effective way of fighting infectious diseases like HIV, malaria, influenza etc. Among the potential needle-free routes, nasal vaccination is particularly attractive. The formulation of antigens in particulate delivery systems can lead to protection of the antigen, co-encapsulation of antigen and adjuvant, potential increase of retention time at the nasal mucosa via bioadhesion, facilitation of the transport of the encapsulated antigen by microfold (M) epithelial cells to the nasal-associated lymphoid tissue (NALT) from where it can be delivered to a lymphatic environment and sustained release of antigen and thus increased presentation time to antigen presenting cells (APCs).

LPBE’s present research activities focus on the development of functionalized biodegradable nanocarriers for vaccination (mainly mucosal) taking into account all important chemical and physical factors which affect carrier stability, antigen & adjuvant loading and release profile and functionalization. The developed nanocarriers meet the vaccination requirements for antigen and adjuvant loading, cytotoxicity & hemocompatibility and are successfully uptaken by cells.

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Particle Size (nm) Stability of PLGA NPs containing ovalbumin and

monophosphoryl lipid A in sucrose solution at 4oC

Well # NPs gel 1 MW 2 OVA 3 blank NPs 4 1wk NPs 5 2wk NPs 6 3wk NPs 7 4wk NPs

1 2 3 4 5 6 71 2 3 4 5 6 7

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Ovalbumin integrity following incubation of PLGA

NPs in PBS for 4 weeks at 25oC.

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Cell uptake of BSA-FITC loaded PLGA NPs after

15min & 24hrs (cell line J774)

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at 37oC LPBE is also involved with the development of nanocarriers for the oral delivery of peptides and proteins (e.g., insulin). Despite the significant barriers to drug delivery in the gastrointestinal tract (GIT), the oral route is well appreciated by considering its obvious advantages (e.g., ease of administration, large patient acceptability, etc.). In addition, oral formulations do not require sophisticated sterile manufacturing facilities, nor the direct involvement of health care professionals.

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MIPs for Protein Separation

One of the most promising technologies for preparing materials of high specificity with applications in the fields of biotechnology, separation, purification, analytical science, etc. is the molecular imprinting, where the presence of a template molecule during polymer synthesis plays a critical role, in creating well-defined sites in the polymer matrix. Additionally, these materials exhibit high physical and chemical resistance against external degrading factors and, thus, they

are remarkably stable against mechanical stresses, high temperatures and pressures and also stable in a wide range of solvents. Furthermore, these polymers can be repeatedly used without loss of their “memory effect”.

Functionalmonomers

Templatemolecule

ComplexFormation

Polymerization

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Functionalmonomers

Templatemolecule

ComplexFormation

Polymerization

Extraction

LPBE is involved in the synthesis of molecularly imprinted nano- and micro-particles (via precipitation, suspension and inverse suspension polymerization methods) in relatively high yield, having controllable physical properties, such as size, morphology and particle strength/resistance.

Both hydrophobic peptides, such as boc-Trp3 and hydrophilic peptides, such as cbz-His-His-ome, His-His-ome, His-Phe-ome, AISYGN and AISYGNGVY have been used as template molecules.

MIPs by precipitation & suspension polymerization

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of tryptophane in suspension polymerization

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Functional Biopolymers

Biodegradable polymers including poly(lactic acid) (PLA) are versatile biomedical materials for surgical sutures, absorbable bone plates, artificial skin, tissue scaffolds, and carriers of drugs for controlled release systems. LPBE is involved in the production of PLA via ring opening polymerization of L,L-lactide. Enzymic catalyzed polymerization reactions are performed under vacuum ensuring minimization of impurities that inhibit the reaction.

Vacuum line

Lipase from Thermus thermophilus is used to catalyze the reaction. The microorganism cultivation is carried out in fed-batch bioreactors in which the investigation of the optimal operating conditions is further facilitated. The lipolytic activity, thermal stability and protein concentration are measured in both extracellular and intracellular enzyme media. The purification of the crude enzyme is assayed with two techniques based on precipitation strategies and the partial purified enzyme is further purified with chromatographic techniques.

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thermophilus HB 8 culture

Polyhydroxyalkanoates (PHAs) is a carbon and energy storage material synthesized by numerous bacteria in response to environmental stress. They are synthesized and deposited intracellularly in the form of inclusion bodies and can amount up to 90% (dry weight) of cells. PHAs can be utilized in drug delivery, bone replacement applications, for making films having excellent gas barrier properties.

LPBE focuses on the microbial production of PHB, aiming at maximising the yield and the production rate as well as at quantitatively

determining factors that have a momentous impact on the molecular and end-use properties of the produced biopolymer. Throughout the production line of PHB, multi-scale modeling of the fermentation process and product characterization studies, providing feedback to the production process, are carried out in parallel.

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PHB accumulation depending on the initial C/N ratio

Biomimetic Gels

To achieve local tissue repair and stimulate healing it is necessary to deliver the appropriate agents or growth factors.

LPBE is involved in the development of hydrogel nanoparticles for the controlled delivery of growth factors. Research also includes testing of the synthesized hydrogels for tissue regeneration in vitro.

Intraarticular delivery of growth factors

In vitro Models for Cell Transport Studies

In vitro models of human bronchial epithelial Calu-3 (mucus-secreting when cultured in an air-liquid interface) cells and human intestinal epithelial Caco-2 cells are used to examine the cells interactions with different NPs / formulations with regard to cell stability, cell morphology, orientation and transport across the cell barrier. The integrity of cell monolayers in vitro is assessed by measuring the transelectrical resistance (TER). Transport of the NPs through the cell barrier is monitored by the analysis of the medium in the apical and basolateral compartment for the presence of NPs (ELISA, microscopy) and by the measurement of the concentration of fluorescently labeled NPs.

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Modeling of Pulmonary & Nasal Delivery

The design of delivery systems for pulmonary drug delivery (PDD) is still more of an art than a well-established engineering discipline. CFD simulations and deposition simulations have been performed but there are many issues still unresolved (e.g., simulation of flow and deposition in the lower respiratory tract, effect of formulation properties on the deposition mechanics, deposition and release in the alveoli).

LPBE has developed a dual-scale simulation model consisting of a CFD model, performed in the entire pulmonary tract, and a small-scale local particle deposition model utilizing the CFD output of the large scale simulation to perform local simulations of particle motion near the mucosa surface. The latter introduces additional forces on the particle as well as geometric details of the particle and the mucosa/cell wall surfaces.

Multiple Branch containing G0-G3 segment

generations

Particle tracking (metallic particles of 5μm)

The goal of modeling of the flow and deposition of carrier droplets/particles in the nasal cavity and the subsequent release of the drug is to optimize the formulation properties and delivery device characteristics. The amount of drug that is delivered to the nasal cavity from inhaled particles depends on many factors including the total amount of deposited particles but also the location of particle deposition.

In another development, LPBE is involved with the development of a model that is based on computational fluid dynamics (CFD) simulations and takes into account morphological differences in the nasal cavity geometry and variations in breathing patterns as well as different nasal inflow conditions.

Nasal geometry & contour plot of the velocity

magnitude at a coronal plane

Bivariate deposition distribution (water droplets of

1μm, Rosin-Rammler distribution)

Population Balance Methods

Population Balance Methods, PBM, are essential to the description of the dynamic behavior of dispersed phase systems consisting of particles, droplets, crystals, cells, and other entities. The mechanisms responsible for the evolution of populations in chemical and biochemical systems include growth, aggregation, breakage, nucleation, inflow/outflow, and others. These mechanisms need to be determined either from experimental data or from first-principles modeling approaches. The resulting integrodifferential equations of the

PBM can be hyperbolic in nature and can include singular source terms (e.g., nucleation) rendering them difficult to solve.

Research at LPBE has led to the development of a number of different computational tools for the solution of univariate PBM including sectional techniques, finite elements methods, and Monte Carlo methods. These have been tested and compared for a number of different problems including aggregation/breakage dominated, growth dominated, and nucleation dominated cases.

Two key challenges are currently being addressed. One is the application of the PBM approach to multivariate populations in which the particle population is distributed in terms of an internal physical property in addition to size. Extensions of the univariate computational tools to solve multivariate PBMs accurately and efficiently is underway. The second challenge is the scale-integration of PBMs with models describing the dynamics of the system at different scales, e.g., smaller scale single-particle dynamics and larger scale mixing models.

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Bivariate particle size distributions. Constant and

Brownian Aggregation from an initial bi-exponential distribution

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Bivariate particle size distributions. Constant

aggregation and size dependent univariate growth, G=G0Va. (a) a=1/3, (b) a=2/3

Polymer Reaction Engineering

The major objective of polymerization reaction engineering is to understand how the reaction mechanism, the physical transport phenomena (e.g., mass and heat transfer, mixing), the reactor type and its operating conditions affect the “polymer quality” of the final product. The term “polymer quality” includes all the molecular chain architecture structural properties (e.g., molar mass, molecular weight distribution (MWD),

copolymer composition distribution (CCD), chain sequence length distribution (CSLD), branching distribution (BD), stereoregularity, etc.) as well as the macroscopic morphological properties of the polymer product (e.g., particle size distribution, porosity, bulk density, etc.). Over the last 25 years, LPBE has produced a large number of Computer Aided Design (CAD) software tools based on the development of modern mathematical models for the design, simulation, optimization and control of the polymer production processes.

LPBE aims at solving scientific and technical problems related to polymerization process technology. The main research objectives in this area include the theoretical and experimental investigation of the polymerization kinetics, the polymerization reactor design & process modeling, control and optimization of polymerization processes. Recent research developments of LPBE are focused on the application of polymer reaction engineering to olefin polymerization processes (e.g., high-pressure autoclaves and tubular reactors, low pressure gas and slurry phase catalytic processes, etc.), heterogeneous polymerization (e.g., emulsion polymerization of multi-monomer systems, suspension polymerization, dispersion polymerization, precipitation polymerization) and several other free-radical polymerization reactors (bulk, solution, etc.). In addition, the measurement and calculation of the multi-component fluid/polymer phase equilibrium as well as the transport properties (diffusivity, permeability, solubility) are required for the successful modeling and simulation of the polymerization systems.

Kinetic Modeling

Single Particle Modeling

Polymer Phase

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Reactor Modeling

TiCl

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Multi-scale integrated modeling approach

Joint molecular weight Long chain branching bivariate distribution

PolymerS Ltd

PolymerS Ltd provides state-of-the-art software tools for the computer-aided design, monitoring, optimization and control of a wide range of industrial polymerization processes. Based on a 30 years experience in mathematical modeling of polymer production processes, as well as on the long-term collaboration with major polymer companies, PolymerS software tools and solutions are designated for increasing the plant efficiency, improving the product quality and reducing the impact to environment.

The software products provide standard interfaces to detailed design, safety and other CAD packages. The different model-based applications can be accessed from the engineer’s windows-based desktop environment and provide full graphical interaction, expert system guidance on how to use the program or making engineering or modeling decisions and built-in training and documentation. An open system architecture has been adopted for the process modeling components as a means for facilitating the development of model-based applications and as a potential avenue for standardization in modeling technology.

Based on an object oriented design environment, various polymerization kinetics, reactors and other unit operations can be readily selected and combined to build a process model. Full access to kinetic parameters, species properties as well as process conditions is allowed. The advanced modeling tools can simulate a wide range of polymerization mechanisms, reaction media and reactor types (e.g., batch, semi-batch and continuous), including:

ü Catalytic solution and slurry olefin (co)polymerization in tank and loop reactors.

ü Catalytic gas-phase olefin (co)polymerization in continuous stirred bed reactors and fluidized bed reactors.

ü High-pressure polyethylene (PE) tubular reactors and autoclaves.

ü Polyvinylchloride (PVC) batch suspension and bulk polymerization reactors.

ü Emulsion (co)polymerization reactors. ü Bulk, solution and suspension free-radical

(co)polymerization in continuous stirred tank and batch reactors.

Equipment

Fourier transform infrared spectrophotometer (Perkin Elmer 2000)

UV-Vis spectrophotometers (Perkin Elmer Lambda 35, 40 & Hitachi U-1800)

Luminescence spectrophotometer (Perkin Elmer LS 45) Microplate reader (BioTek Instruments Inc., EL808IU-PC) Dynamic light scattering (Malvern Zetasizer nanoZS90) Laser diffraction particle size analyzer (Malvern

Mastesizer 2000) Multi stage liquid impinger (MSLI, Copley) Apparatus for interfacial tension measurements (Krüss,

Typ K10T) Colony counter (Reichert) (LEICA, QUEBEC) Scanning probe microscope (Digital Instr., Nanoscope

IIIa) Optical Microscope - Image analysis system (Leika

Optical Micro DM400B- Leitz Mettalux 3 Leika IM) Stereomicroscope – Image analysis (NIKON, Model SMZ-

2T) Fluorescent microscope – image analysis (DM 4000 B,

Leica & Leica DFC 490) Inverse Microscope (Leica DM IL) Differential scanning calorimeters (TA Q100 & Perkin

Elmer DSC-7) Thermogravimetric analyzer (Perkin Elmer TGA-7) Dynamic mechanical analyzer (Perkin Elmer TAC 7/DX) Dynamic Stress Rheometer (Rheometric Scientific, SR-

5000) Apparatus for intrinsic viscosity measurements

High temperature gel permeation chromatograph with multiple detectors (PL-GPC210, PolymerLabs)

GC-head space chromatograph (Hewlett Packard 6890 & 7694)

GC chromatograph (Agilent Technologies Model GC 6890 N)

High performance liquid chromatography (Agilent Technologies 1200 series) – Mass Spectrometer (Model G6110A)

Low temperature UV-polymerization cabinet (Velp scientifica, FOC 225E)

Sterilizable-in-place, stainless steel fermentor & bioreactor (New Brunswick Scientific Co., INC, BioFlo 410, 7L)

Autoclavable glass fermentor & bioreactor (New Brunswick Scientific Co., INC, BioFlo 110, 3L)

Fully automated, high-pressure stirred autoclaves for polymer production (2L, 2x4L & 8.5L)

Polymerization reactor for experiments in scCO2 Low-pressure stirred reactor 5100 (PARR

INSTRUMENTS, Model 5103, 0.6L) View cells (constant and variable volume) Fluidized bed particle coating device (UniGlatt) Extrusion device for the synthesis of liposomes

(LiposoFast-Pneumatic, avestin Inc.) Freeze dryers (Thermo Electron Corp. Micro Modulyo) Rotary evaporators (Heidolph Laborata 4001 & 4002) Ultra centrifuge (Sorvall, Discovery 100SE) SPEED-VAC Concentrator (Thermo electron corp. Savant

ISS110-230) Centrifuge (BIOFUGE primo R, Heraeus) Centrifuge (Megafuge 1.0R, Hereaus), rotor (Thermo

Heraeus) High precision microbalances (Mettler Toledo MX5-

Mettler Toledo Plus XP & Model XP 105 Delta Range) High-precision sorption microbalance Laminar flows (Kendro Heraeus, Model HERAsafe KS 12

& Thermo Electron Hera Safe KS12- Telstar Bio II A/P) Low temperature incubator (Raypa) Shaker incubator (GFL 3033) CO2 incubator (Heraeus, HeraCell 150) Horizontal autoclave (21L, Raypa, AH-21-N) Deep freezer for cell cryo-preservation (Sanyo, Hellenic

labware) Sonicators (2 x Sonics Vibra Cell VC-505 & Sonics vibra

cell VC600) Homogenizers (Kinematika Ag) Thermomixer (Eppendorf) Tilt shaker (Johanna Otto) Transepithelial electrical resistance (TEER) voltometer PH-meters (Mettler Toledo, Seven Multi)

Recent Journal Publications

Kotrotsiou, O., Chaitidou, S., Liakopoulou-Kyriakides, M. and Kiparissides, C., “Molecularly Imprinted Polymers for Selective Recognition of Biomolecules”, accepted in Journal of Nanostructured Polymers and Nanocomposites, (2008).

Chaitidou, S., Kotrotsiou, O., Kotti, K., Kammona, O., Bukhari, M. and Kiparissides, C. “Precipitation Polymerization for the Synthesis of Nanostructured Particles”, Materials Science and Engineering B 152, 55-59 (2008).

Kiparissides, C. and Kammona, O. “Nanotechnology Advances in Controlled Drug Delivery Systems”, Physica Status Solidi (c) 5(12), 3828-3833 (2008).

Patronidou, C., Karakosta, P., Kotti, K., Kammona, O., Karageorgiou, V. and Kiparissides, C. “PLGA Nanocarriers for Systemic and Lymphatic Oral Delivery of Proteins and Peptides”, Journal of Controlled Release 132, e5-e6 (2008).

Chaitidou, S., Kotrotsiou, O. and Kiparissides, C., “On the Synthesis and Rebinding Properties of [Co(C2H3O2)2(z-Histidine)] Imprinted Polymers Prepared by Precipitation Polymerization”, accepted to Materials Science and Engineering C (2008).

Κυπαρισσίδης, Κ., Καμμώνα, Ο. και Χαϊτίδου, Σ. “Εφαρμογές Νανοτεχνολογίας στην Ιατρική”, Intellectum 4, 5-20 (2008).

Alexopoulos, A.H., Roussos, A., and Kiparissides, C. “Part V: Dynamic Evolution of the Multivariate Particle Size Distribution Undergoing Combined Particle Growth and Aggregation” Chemical Engineering Science, 64(14), 3260-3269 (2009).

Alexopoulos, A.H. and Kiparissides, C. “Solution of the Bivariate Dynamic Population Balance Equation in Batch Particulate Systems: Combined Aggregation and Breakage” Chemical Engineering Science, 62(18), 5048-5053 (2007).

Dompazis, G., Kanellopoulos, V., Touloupides, V. and Kiparissides, C. “Development of a Multi-scale, Multi-phase Multi-zone Dynamic Model for the Prediction of Particle Segregation in Catalytic Olefin Polymerization FBRs”, Chemical Engineering Science, 63, 4735-4753 (2008).

Krallis, A., Meimaroglou, D. and Kiparissides, C., “Dynamic Prediction of the Bivariate Molecular Weight – Copolymer Composition Distribution Using Sectional-Grid and Stochastic Numerical Methods”, ChemEngiSci, 63, 4342-4360 (2008).

Kanellopoulos, V., Gustafsson, B. and Kiparissides, C., “Gas-phase Olefin Polymerization in the Presence of Supported and Self-supported Ziegler-Natta Catalysts”, Macromolecular Reaction Engineering, 2, 240-252 (2008).

Pladis, P, Kanellopoulos, V., Chatzidoukas, Ch. and Kiparissides, C., “Effect of Reaction Conditions and Catalyst Design on the Rheological Properties of

Polyolefins Produced in Gas-phase Olefin Polymerization Reactors”, Macromolecular Theory and Simulation, 17(9), 478-487 (2008).

Krallis, A. and Kiparissides, C., “Computer Aided Design and Operation of Industrial Poly(Vinyl Chloride) Batch Suspension Polymerization Reactors”, Plastics, Rubber and Composites: Macromolecular Engineering (PRC:ME), 37, 436-441 (2008).

Recent Conference Papers

Kiparissides, C., “Recent Advances in Nanomedicine”, 2nd International School and Workshop on INSIDE-POReS), Thessaloniki, Greece, February 24-28, 2007.

Kotrotsiou, O., Chaitidou, S. and Kiparissides, C., “Molecularly Imprinted Polymers for Selective Recognition of Biomolecules”, 3rd International Symposium on Nanostructured and Functional Polymer-Based Materials and Nanocomposites, Corfu, Greece, May 13-15, 2007.

Kiparissides, C., “Protein-Peptide Delivery through Pulmonary and Oral Delivery Routes”, 4th pHealth Conference, Porto Carras, Chalkidiki, Greece, June 20-22, 2007.

Penloglou G., Roussos A.I., Karidi K., Chatzidoukas C. and Kiparissides C., “Optimal Production of Polyhydroxybutyrate (Phb) in Alcaligenes Latus through Metabolic Engineering Analysis”, European Polymer Congress (EPF2007), Portoroz, Slovenia, July 2-6, 2007.

Mantourlias T., Roussos A.I., Chatzidoukas C. and Kiparissides C., “Prediction of the Molecular Weight Distribution in Lipase-Catalyzed Ring-Opening Polymerization of e-Caprolactone”, European Polymer Congress (EPF2007), Portoroz , Slovenia, July 2-6, 2007.

Chaitidou, S., Kotrotsiou, O., Kotti, K., Kammona, O. and Kiparissides, C., “Synthesis of Nanostructured Particles for Environmental and Bio-Analytical Applications”, 4th International Workshop on “Nanosciences & Nanotechnologies” (NN07), Thessaloniki, Greece, July 16-18, 2007.

Patronidou, Chr., Karakosta, P., Kotti, K., Kammona, O., Karageorgiou, V. and Kiparissides, C., “Functionalized Nanocarriers for Oral and Pulmonary Delivery of Proteins and Peptides”, 4th International Workshop on Nanosciences & Nanotechnologies (NN07), Thessaloniki, Greece, July 16-18, 2007.

Kotti, K., Kammona, O., Kotrotsiou, O., Chaitidou. S. and Kiparissides, C., “Polymeric Micro- and Nanocarriers for Drug Delivery Applications”, International Conference on Nanomedicine, Chalkidiki, Greece, September 9-11, 2007.

Patronidou, Chr., Karakosta, P., Kotti, K., Kammona, O., Karageorgiou V. and Kiparissides, C., “Synthesis of Functionalized Nanocarriers for Oral and Pulmonary Delivery of Protein and Peptide Drugs”, International Conference on Nanomedicine, Chalkidiki, Greece, September 9-11, 2007.

Kiparissides, C., “Nanotechnology Advances in Controlled Drug Delivery Systems”, 3rd International Conference “Micro&Nano2007” on Micro- Nanoelectronics, Nanotechnology and MEMs, Athens, Greece, October 18-21, 2007.

Penloglou, G., Roussos, A.I., Chatzidoukas, C. and Kiparissides, C. “Model-Based Investigation of the Microbial Production of Polyhydroxyalcanoates (Phas)”, Computer Aided Process Engineering – Forum, Thessaloniki, Greece, February 7-8, 2008.

Kiparissides, C. “Application of Multi-dimensional Population Balance Equations to Polymerization & Biochemical Systems: Computational Methods and Experimental Validation”, 1st European Conference on Process Analytics and Control Technology – EUROPACT, Frankfurt, Germany, Apri 22-25, 2008.

Kiparissides, C., “Microbial and Biocatalytic Production of Advanced Functional Polymers”, Entretiens du Centre Jacques Cartier, Modelling, Monitoring and Control of Polymer Properties, ESCPE-Lyon, France, December 3-5, 2007.

Kiparissides, C. and Chatzidoukas, C. “Microbial and Biocatalytic Production of Advanced Functional Polymers”. Computer Aided Process Engineering – Forum, Thessaloniki, Greece, February 7-8, 2008.

Patronidou, Chr, Karakosta, P., Kotti, K., Kammona, O., Karageorgiou, V. and and Kiparissides, C. “PLGA Nanocarriers for Systemic and Lymphatic Oral Delivery of Proteins and Peptides”, 10th European Symposium on Controlled Drug Delivery, Enschede, The Netherlands, April 2-4, 2008.

Kiparissides, C. and Kammona, O., “Nanotechnology Advances in Controlled Drug Delivery Systems”, 5th Chemical Engineering Conference for Collaborative Research in Eastern Mediterranean Countries (EMCC-5), Cetraro, Italy., May 24-29, 2008.

Kiparissides, C. “Microbial and Biocatalytic Production of Advanced Functional Polymers”, Biomacromolecules, Stockholm, Sweden, June 2-4, 2008.

Kiparissides, C. “Nanotechnology Advances in Controlled Drug Delivery Systems”, NanoBio-Europe2008, Barcelona, Spain, June 9-13, 2008.

Patronidou, Chr, Karakosta, P., Kotti, K., Kammona, O., Karageorgiou, V. and Kiparissides, C., “Functionalized Plga Nanoparticles for Protein Delivery”, 1st International Conference from Nanoparticles and Nanomaterials to Nanodevices and Nanosystems, Halkidiki, Greece, June 16-18, 2008.

Kiparissides, C., “Recent Advances in Nanomedicine”, 1st International Conference from Nanoparticles and Nanomaterials to Nanodevices and Nanosystems, Halkidiki, Greece, June 16-18, 2008.

Kotrotsiou, O., Chaitidou, S. and Kiparissides C., “Peptide Imprinted Polymers by Suspension Polymerization”, 5th International Conference on Nanosciences & Nanotechnologies (NN08), Thessaloniki, Greece, July 14-16, 2008.

Chaitidou, S., Kotrotsiou, O. and Kiparissides C., “On the Epitope Approach: Oligopeptide Imprinted Polymers via Conventional and Inverse Suspension Polymerization”, 2008 AIChE Annual Meeting, Philadelphia, USA, November 16-21, 2008.

Penloglou G., Roussos A.I., Chatzidoukas C. and Kiparissides C., “Fermentative Poly(3-hydroxybutyrate) Production in Alcaligenes latus. A Combined Metabolic/kinetic Modelling Approach”, 2008 AIChE Annual Meeting, Philadelphia, USA, November 16-21, 2008.

Kotti, K., Karageorgiou, V., Patronidou, C., Kammona, O. and Kiparissides, C., “PLGA Nanocarriers for Nasal Vaccination”, 36th Annual Meeting of the Controlled Release Society, 18-22 July 2009, Copenhagen, Denmark.

Kotti, K., Karageorgiou, V., Patronidou, C., Kammona, O. and Kiparissides, C., “Synthesis of PLGA Nanoparticles for Lymphatic Nasal Delivery of Proteins”, submitted to 6th International Conference on Nanosciences and Nanotechnologies (NN09), Thessaloniki, Greece, 13-15 July, 2009.

Karakosta, P., Alexopoulos, A.H. and Kiparissides C., “Computational Model of Drug Release in the Nasal Cavity”, submitted to 6th International Conference on Nanosciences and Nanotechnologies (NN09), Thessaloniki, Greece, 13-15 July, 2009.

Kotti, K., Karageorgiou, V., Patronidou, C., Kammona, O. and Kiparissides, C., “Synthesis of PLGA Nanocarriers for Nasal Vaccination”, EuroNanoMedicine 2009, Bled, Slovenia, 28-30 September, 2009.

Alexopoulos, A.H., Karakosta, P. and Kiparissides C., “Computational Model of Drug Release in the Nasal Cavity”, EuroNanoMedicine 2009, Bled, Slovenia, 28-30 September, 2009.

Kotti, K., Karageorgiou, V., Patronidou, C., Kammona, O. and Kiparissides, C., “Synthesis of PLGA Nanocarriers for Lymphatic Nasal Delivery of Proteins”, AIChE 2009 Annual Meeting, Nashville, USA, 8-13 November, 2009.

Alexopoulos, A.H., Karakosta, P. and Kiparissides C., “Computational Model of Drug Release in the Nasal Cavity”, AIChE 2009 Annual Meeting, Nashville, USA, 8-13 November, 2009.

Alexopoulos, A.H. and Kiparissides, C. “Dynamic Evolution of Bivariate Particle Size Distributions in Particulate Processes”, 3rd International Conference on Population Balance Modeling, Quebec City, Canada, Sept. 18-20, 2007.

Kanellopoulos, V, Gustafsson, B, Touloupides, V. and Kiparissides, C., “Gas-phase Olefin Polymerization in the Presence of Supported and Self-supported Ziegler-Natta Catalysts”, Hangzhou International Polymer Forum: Advanced Materials and Reaction Engineering, Hangzhou, May 13-17, 2007.

Pladis, P., Kanellopoulos, V., Chatzidoukas, C. and Kiparissides, C., “Effect of Reactor Conditions and Catalyst Design on Rheological Behavior of Polymers

Produced in Catalytic Olefin Polymerization FBRs”, European Congress on chemical Engineering (ECCE-6), Copenhagen, Denmark, September 16-21, 2007.

Touloupides, V., Dompazis, G., Kanellopoulos, V. and Kiparissides, C. “Dynamic Simulation of Catalytic Olefin Polymerization in Continuous Gas and Slurry Phase Reactors”, 6th Chemical Engineering Conference, Athens, Greece, 31 May - 02 June, 2007.

Dompazis G., Kanellopoulos V., Touloupides V. and Kiparissides C., “Development of a Dynamic Multi-compartment Model for the Prediction of Particle Size Distribution and Molecular Properties in a Catalytic Olefin Polymerization FBR”, 3rd International Conference on Population Balance Modelling, Québec City – Canada, September 19-21, 2007.

Meimaroglou, D., Krallis, A. and Kiparissides, C., “Dynamic Monte Carlo Simulation of Batch Free-radical Linear and Non-linear Copolymerization Systems”, European Congress on chemical Engineering (ECCE-6), Copenhagen, Denmark, September 16-21, 2007.

Pladis, P., Kanellopoulos, V., Chatzidoukas, C. and Kiparissides, C., “Effect of Reactor Conditions and Catalyst Design on Rheological Behavior of Polymers Produced in Catalytic Olefin Polymerization FBRs”, 6th Modelling, Monitoring and Control of Polymer Properties, Lyon, France, 1-5 December, 2007.

Krallis, A. and Kiparissides, C. “Computer Aided Design and Operation of Industrial Poly(Vinyl Chloride) Batch Suspension Polymerization Reactors”, 10th International Conference on PVC, Innovation – Technology – Sustainability – Networking, Brighton Dome, UK, Apri 22-24, 2008.

Pladis, P., Krallis, A., Baltsas, A. and Kiparissides C., “A Comprehensive Software Package for the Dynamic Simulation of High Pressure Ldpe Plants”, 1st International Conference on the Reaction Engineering of Polyolefins – INCOREP, Montreal, Canada, June 22-27, 2008.

Krallis, A., Pladis, P. and Kiparissides C., “Comprehensive Modeling of the Bivariate MW-LCB Distribution of LDPE Produced in High-Pressure Autoclaves”, Polymer Reaction Engineering 7, (PRE 7), Niagara Falls, Ontario, Canada, 3-8 May, 2009.

Kiparissides, C., Pladis, P., Kanellopoulos, V. and Krallis, A., “Modeling of Rheological Behavior of Polymers Produced in Catalytic Olefin Polymerization Reactors”, (EPF), Graz, Austria, 12-17 July, 2009.

Kiparissides, C., Pladis, P., Baltsas, A., Kanellopoulos, V. and Krallis, A., “Modeling of High and Low Pressure Separators in High Pressure LDPE Plants”, (EPF), Graz, Austria, 12-17 July, 2009.

Touloupides, V., Kanellopoulos, V., Pladis, P., Krallis, A. and Kiparissides, C. “Real-time Simulation of an Industrial Scale Slurry Loop Reactor”, 8th World Congress of Chemical Engineering (WCCE8), Montreal, Canada, 23-27 August, 2009.

Meimaroglou D., Pladis P., Krallis A. and Kiparissides C., ‘Prediction of MWD and Topological Characteristics of LDPE in High-Pressure Reactors’, 8th World Congress of Chemical Engineering, (WCCE8), Montreal, Canada, 23-27 August, 2009.

Touloupides, V., Kanellopoulos, V., Pladis, P., Krallis, A. and Kiparissides, C., “Modeling and Simulation of Slurry-Phase Olefin Catalytic Polymerization Industrial Loop Reactors. Prediction of Polymer Particle Growth, Molecular, Rheological and Morphological Polymer Properties”, AIChE 09 Annual Meeting, Nashville, USA, November 8-13, 2009.

Contact Information

Professor Costas Kiparissides

Department of Chemical Engineering, AUTh, & Chemical Process Engineering Research Institute, CERTH, P.O. Box 472, 54124 Thessaloniki, Greece

Tel: +30 2310 996211, 996212, 498211 Fax: +30 2310 996198, 498110 E-mail: [email protected] [email protected] Web site: http://www.cperi.certh.gr/lpre

LPBE Visiting Addresses:

Aristotle University of Thessaloniki Polytechnic School Department of Chemical Engineering Building E13 (4th floor)

Centre for Research and Technology Hellas

Chemical Process Engineering Research Institute 6th Km Charilaou-Thermi Rd

mailto:[email protected]

mailto:[email protected]

http://www.cperi.certh.gr/lpre

laboratory of polymer & biochemical engineering...

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