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. 1996 May 28;93(11):5460–5465. doi: 10.1073/pnas.93.11.5460

Irreversible inactivation of interleukin 2 in a pump-based delivery environment.

S T Tzannis 1, W J Hrushesky 1, P A Wood 1, T M Przybycien 1
PMCID: PMC39268  PMID: 8643597

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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