Physical stability of albinterferon-α(2b) in aqueous solution: effects of conformational stability and colloidal stability on aggregation.
Controlling aggregation in protein therapeutics is a significant challenge. In this study, the aggregation behavior of albinterferon-α(2b) , a genetic fusion protein combining human serum albumin and α-interferon, was examined as a function of solution conditions. The stability was monitored during agitation and during storage at elevated temperature, where the extent of aggregation was determined using size-exclusion chromatography. The osmotic second virial coefficient and the free energy of unfolding were measured for each sample. This study demonstrates that both increasing conformational stability and maximizing colloidal stability help to maintain the physical stability of albinterferon-α(2b).
Center for Pharmaceutical Biotechnology, University of Colorado Denver Health Sciences Center, Aurora, Colorado, USA.
Danny K
DK
Chou
Rajesh
R
Krishnamurthy
Mark Cornell
MC
Manning
Theodore W
TW
Randolph
John F
JF
Carpenter
D000418:Albumins / Q000737:chemistry*; D002850:Chromatography, Gel; D003102:Colloids / Q000737:chemistry; D004355:Drug Stability; D006358:Hot Temperature; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry*; D011487:Protein Conformation; D055550:Protein Stability; D058767:Protein Unfolding; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012995:Solubility; D014508:Urea / Q000737:chemistry
D000418:Albumins; D003102:Colloids; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; C531108:albinterferon alfa-2b; D014508:Urea