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The Impact of Formulated Interleukin-2 / Delivery Device Surface Interactions on Bioefficacy

Published online by Cambridge University Press:  15 February 2011

Stelios T. Tzannis ,
Todd M. Przybycien ,
William J. M. Hrushesky  and
Patricia Wood
Stelios T. Tzannis
Affiliation:
Rensselaer Polytechnic Institute, The Howard P. Isermann Department of Chemical Engineering, Troy NY 12180
Todd M. Przybycien
Affiliation:
Rensselaer Polytechnic Institute, The Howard P. Isermann Department of Chemical Engineering, Troy NY 12180
William J. M. Hrushesky
Affiliation:
Stratton VA Medical Center, Department of Medical Oncology, Albany, NY 12208
Patricia Wood
Affiliation:
Stratton VA Medical Center, Department of Medical Oncology, Albany, NY 12208
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Abstract

The interactions between a therapeutic protein and the surfaces of a delivery device may play a pivotal role in the efficacy of a recombinant protein-based biologic therapy program. Protein adsorption may induce conformational changes and aggregation, resulting in the inactivation of the protein of interest and even malfunction of the delivery device itself. We studied the interactions of formulated interleukin-2 (IL-2) with the surfaces of a commonly used pump-based delivery system at 37°C over a 24-hour period. Delivered protein concentration and bioactivity assays were performed at intervals in order to quantitate the impact of exposure time. Adsorption to the catheter tubing walls resulted in 20 to 30% reduction in the concentration of delivered IL-2 relative to the initial concentration. After 2 hours of operation, delivered IL-2 bioactivity levels fell to -10% of the initial activity levels. These activity losses were accompanied by a significant decrease in the protein's helical content, as monitored by circular dichroism spectroscopy. Attenuated total reflectance Fourier transform infrared spectroscopy indicated that adsorbed IL-2 had non native secondary structure contents. We hypothesize that surface-mediated IL-2 denaturation is responsible for the majority of the observed activity losses

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 331: Symposium T – Biomaterials for Drug and Cell Delivery , 1993 , 227
Copyright
Copyright © Materials Research Society 1994

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