Chemical Engineering News

Dr. Todd M. Przybycien

 Carnegie Mellon University

Departments of Chemical Engineering and Biomedical Engineering 

Friday-February 22, 2013

10:00am

MUB- Alumni Lounge

Unconventional Applications of Poly(ethylene glycol)-modified Proteins in BioProcessing and Drug Delivery

The covalent attachment of poly(ethylene glycol) (PEG) polymer chains, or “PEGylation,” improves the efficacy of protein drugs by extending their half-lives in the circulation without adversely affecting biological binding activity: the PEG chains are thought to hinder recognition by proteases, inhibitors and antibodies through steric interactions and to retard renal clearance through increased molecular size.  We used a more complete understanding of the solution and interfacial adsorption behavior of PEG-protein conjugates to explore new applications of protein PEGylation in bioprocessing and drug delivery. 

We have developed new, high selectivity protein affinity chromatography media by PEGylating immobilized protein affinity ligands outside of the target binding site.  This discourages the non-specific binding of contaminant species without decreasing target binding.  We find selectivity enhancements for IgG-class antibodies of 2x to 3x for Protein A affinity chromatography media modified with 5 kDa and 20 kDa PEG chains relative to the un-modified media, without loss of antibody binding affinity.  Increased contaminant rejection by Protein A media has important implications for simplifying downstream processing operations for monoclonal antibody production and for extending the operating lifetime of this expensive class of bioseparations media.

We have exploited PEGylation to reduce denaturing adsorptive interactions between proteins and interfaces that limit the successful delivery of protein drugs from poly(lactide-co-glycolide) (PLG) microsphere delivery systems. Oil/water interfaces are present during the generation of protein-loaded PLG microspheres by the double emulsion technique and solid/water interfaces are present as the microspheres erode during delivery.  The depressed adsorption isotherms of conjugates reduce the extent of adsorption at denaturing interfaces and the attached PEG random coils serve as steric diluents at interfaces.  While PEGylation with 20 kDa PEG has little effect on protein behavior at ethyl acetate/water interfaces, at PLG/water interfaces we find decreased extents of adsorption, increased reversibility of adsorption and decreased tendency to aggregate.  These results have translated to ~50% and ~100% improvements in active protein release for monoPEGylated and diPEGylated ribonuclease A, respectively.

Dr. Thomas Werner, Assistant Professor

Michigan Technological University

Department of Biological Sciences

Friday-February 8, 2013

MUB Ballroom B at 10:00am

The role of toolkit genes in the evolution of complex wing, thorax, and abdominal color patterns in Drosophila guttifera.

Animal color patterns such as zebra stripes, leopard spots, and the myriad variants of butterfly wing color patterns are known to play important ecological and physiological roles in the life of animals and are crucial for the survival of species. Scientists first tried to solve the secret of animal patterns with mathematical approaches to find models that could explain how these patterns developed. In 1952, Turing proposed the famous reaction-diffusion model in which a short-range acting activator molecule diffuses from a source to stimulate color production, while a long-range acting inhibitor molecule prevents pigmentation. Using the spectacularly ornamented fruit fly Drosophila guttifera, we developed a transgenic protocol to study the development and evolution of color patterns. We identified that the Wingless morphogen had evolved a new function in the D. guttifera lineage by activating the yellow gene on pre-existing structural landmarks on the wing, causing black melanin spots around sensory organs, tips of the veins, and crossveins. We are currently expanding this work by investigating if the melanin patterns on different body parts of D. guttifera evolved by the same mechanisms involving Wingless, or if they have independently evolved

November 9: Dr. Megan C. Frost- Grain Processing Seminar Series in Chemical Engineering

Friday-November 9, 2012 at 10:00am

Fisher Hall, Room 139

Dr. Megan C. Frost, Assistant Professor

Department of Biomedical Engineering at Michigan Technological University

Topic: Developing Nitric Oxide Releasing Polymers and Test Platform to Understand  Cellular Response to Nitric Oxide

Polymeric materials used to coat or construct biomedical devices universally inspire a foreign body response when in contact with a biological system (e.g., thrombus formation on the polymer surface when in contact with blood, inflammatory response in subcutaneous tissue, etc.). Nitric oxide (NO) is a highly reactive free radical gas that has been shown to have a number positive of physiological functions at appropriate levels, including serving as a potent inhibitor of platelet adhesion and activation and mediating the inflammatory response. An NO-releasing silicone rubber coating was developed that contains a photosensitive S-nitrosothiol NO-donors that utilizes light as an external on/off trigger to initiate NO release. This material   shows dynamically controllable NO release based on the duration and intensity of light irradiating the material and offers  precise control of the level and duration of NO delivered at the tissue/polymer interface. We have also developed a test platform that allows quantitative levels of NO to be delivered to cells in vitro to further understanding of cellular response to NO.