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

doi:10.1023/A:1018935420680

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 journal › Article › peer-review

48 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 language	English (US)
Pages (from-to)	1004-1008
Number of pages	5
Journal	Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume	11
Issue number	7
DOIs	https://doi.org/10.1023/A:1018935420680
State	Published - 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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Vrkljan, M., Foster, T. M., Powers, M. E., Henkin, J., Porter, W. R., Staack, H., Carpenter, J. F., & Manning, M. C. (1994). Thermal Stability of Low Molecular Weight Urokinase During Heat Treatment. II. Effect of Polymeric Additives. Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, 11(7), 1004-1008. https://doi.org/10.1023/A:1018935420680

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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.",

keywords = "additives, polymeric, aggregation, formulation, protein stability, turbidimetry, urokinase",

author = "Michael Vrkljan and Foster, {Thomas M.} and Powers, {Michael E.} and Jack Henkin and Porter, {William R.} and Harold Staack and Carpenter, {John F.} and Manning, {Mark C.}",

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Vrkljan, M, Foster, TM, Powers, ME, Henkin, J, Porter, WR, Staack, H, Carpenter, JF & Manning, MC 1994, 'Thermal Stability of Low Molecular Weight Urokinase During Heat Treatment. II. Effect of Polymeric Additives', Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, vol. 11, no. 7, pp. 1004-1008. https://doi.org/10.1023/A:1018935420680

Thermal Stability of Low Molecular Weight Urokinase During Heat Treatment. II. Effect of Polymeric Additives. / Vrkljan, Michael; Foster, Thomas M.; Powers, Michael E. et al.

In: Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, Vol. 11, No. 7, 07.1994, p. 1004-1008.

Research output: Contribution to journal › Article › peer-review

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AU - Vrkljan, Michael

AU - Foster, Thomas M.

AU - Powers, Michael E.

AU - Henkin, Jack

AU - Porter, William R.

AU - Staack, Harold

AU - Carpenter, John F.

AU - Manning, Mark C.

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

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Keywords

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