Thermal Stability of Low Molecular Weight Urokinase During Heat Treatment. II. Effect of Polymeric Additives

Michael Vrkljan, Thomas M. Foster, Michael E. Powers, Jack Henkin, William R. Porter, Harold Staack, John F. Carpenter, Mark C. Manning*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    46 Scopus citations

    Abstract

    Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60°C heat treatment, LMW-UK initially denatures and the unfolded protein associates to form soluble aggregates. Eventually, these aggregates associate to form a precipitate. The effects of polymers on the initial aggregation phase was examined. Hydroxyethyl (heta) starch, polyethylene glycol 4000, and gelatin were found to be effective, concentration-dependent inhibitors of aggregation, whereas polyvinylpyrrolidone (PVP) and polyethylene glycol 300 were ineffective. Overall, the effect of polymeric additives on the stability of thermally-stressed LMW-UK can be accounted for by preferential exclusion of the solute from the surface of the protein.

    Original languageEnglish (US)
    Pages (from-to)1004-1008
    Number of pages5
    JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
    Volume11
    Issue number7
    DOIs
    StatePublished - Jul 1994

    Keywords

    • additives, polymeric
    • aggregation
    • formulation
    • protein stability
    • turbidimetry
    • urokinase

    ASJC Scopus subject areas

    • Biotechnology
    • Molecular Medicine
    • Pharmacology
    • Pharmaceutical Science
    • Organic Chemistry
    • Pharmacology (medical)

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