Irreversible inactivation of interleukin 2 in a pump-based delivery environment.
The physical stability of pharmaceutical proteins in delivery environments is a critical determinant of biological potency and treatment efficacy, and yet it is often taken for granted. We studied both the bioactivity and physical stability of interleukin 2 upon delivery via continuous infusion. We found that the biological activity of the delivered protein was dramatically reduced by approximately 90% after a 24-hr infusion program. Only a portion of these losses could be attributed to direct protein deposition on the delivery surfaces. Analysis of delivered protein by size exclusion chromatography gave no indication of insulin-like, surface-induced aggregation phenomena. Examination of the secondary and tertiary structure of both adsorbed and delivered protein via Fourier-transform infrared spectroscopy, circular dichroism, and fluorescence spectroscopy indicated that transient surface association of interleukin 2 with the catheter tubing resulted in profound, irreversible structural changes that were responsible for the majority of the biological activity losses.
Tzannis
S T
ST
The Howard P. Isermann Department of Chemical Engineering, Applied Protein Biophysics Laboratory, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
Hrushesky
W J
WJ
Wood
P A
PA
Przybycien
T M
TM
D020106:Acrylamide; D000178:Acrylamides; D000327:Adsorption; D000818:Animals; D001681:Biological Assay; D002460:Cell Line; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004355:Drug Stability; D004926:Escherichia coli; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000737:chemistry*; D008213:Lymphocyte Activation; D051379:Mice; D011193:Potassium Iodide; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
D000178:Acrylamides; D007376:Interleukin-2; D011994:Recombinant Proteins; D011193:Potassium Iodide; D020106:Acrylamide