| Literature DB >> 7937540 |
M Vrkljan1, T M Foster, M E Powers, J Henkin, W R Porter, H Staack, J F Carpenter, M C Manning.
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 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.Entities:
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Year: 1994 PMID： 7937540 DOI： 10.1023/a:1018935420680
Source DB: PubMed Journal: Pharm Res ISSN： 0724-8741 Impact factor: 4.200