Thermal stability of low molecular weight urokinase during heat treatment. II. Effect of polymeric additives

Autor: M, Vrkljan, T M, Foster, M E, Powers, J, Henkin, W R, Porter, H, Staack, J F, Carpenter, M C, Manning
Rok vydání: 1994
Předmět:
Zdroj: Pharmaceutical research. 11(7)
ISSN: 0724-8741
Popis: 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 degrees 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.
Databáze: OpenAIRE