title: Approaches for increasing the solution stability of proteins.
abstract: Stabilization of proteins through proper formulation is an important challenge for the pharmaceutical industry. Two approaches for stabilization of proteins in solution are discussed. First, work describing the effect of additives on the thermally induced denaturation and aggregation of low molecular weight urokinase is presented. The effects of these additives can be explained by preferential exclusion of the solute from the protein, leading to increased thermal stability with respect to denaturation. Diminished denaturation leads to reduced levels of aggregation. The second approach involves stoichiometric replacement of polar counter ions (e.g., chloride, acetate, etc.) with anionic detergents, in a process termed hydrophobic ion pairing (HIP). The HIP complexes of proteins have increased solubility in organic solvents. In these organic solvents, where the water content is limited, the thermal denautration temperatures greatly exceed those observed in aqueous solution. In addition, it is possible to use HIP to selectively precipitate basic proteins from formulations that contain large amounts of stabilizers, such as human serum albumin (HSA), with a selectivity greater than 2000-fold. This has been demonstrated for various mixtures of HSA and interleukin-4. (c) 1995 John Wiley & Sons, Inc.
authors.affiliation: Cooperative Program in Pharmaceutical Biotechnology and Department of Pharmaceutical Sciences, School of Pharmacy, Campus Box C238, University of Colorado Health Sciences Center, Denver, Colorado 80262.
authors.forename: M C
authors.initials: MC
authors.lastname: Manning
authors.forename: J E
authors.initials: JE
authors.lastname: Matsuura
authors.forename: B S
authors.initials: BS
authors.lastname: Kendrick
authors.forename: J D
authors.initials: JD
authors.lastname: Meyer
authors.forename: J J
authors.initials: JJ
authors.lastname: Dormish
authors.forename: M
authors.initials: M
authors.lastname: Vrkljan
authors.forename: J R
authors.initials: JR
authors.lastname: Ruth
authors.forename: J F
authors.initials: JF
authors.lastname: Carpenter
authors.forename: E
authors.initials: E
authors.lastname: Sheftert