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Formulation Design of Acidic Fibroblast Growth Factor (1993)

Tsai, P. K. ; Volkin, David B. ; Dabora, Jonathan M. ; [et al.]

Springer

Pharmaceutical research 10 (1993), S. 649-659

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ISSN: 1573-904X

Keywords: acidic flbroblast growth factor ; protein stability ; polyanions ; protein formulation

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract The design of an aqueous formulation for acidic fibroblast growth factor (aFGF) requires an understanding of the type of compounds that can either directly or indirectly stabilize the protein. To this end, spectrophotometric turbidity measurements were initially employed to screen the ability of polyanionic ligands, less specific compounds, and variations in solution conditions (temperature and pH) to stabilize aFGF against heat-induced aggregation. It was found that in addition to the well-known protection of aFGF by heparin, a surprisingly wide variety of polyanions (including small sulfated and phosphorylated compounds) also stabilizes aFGF. These polyanionic ligands are capable of raising the temperature at which the protein unfolds by 15–30°C. Many commonly used excipients were also observed to stabilize aFGF in both the presence and the absence of heparin. High concentrations of some of these less specific agents are also able to increase the temperature of aFGF thermal unfolding by as much as 6–12°C as shown by circular dichroism and differential scanning calorimetry. Other compounds were found which protect the chemically labile cysteine residues of aFGF from oxidation. Aqueous formulations of aFGF were thus designed to contain both a polyanionic ligand that enhances structural integrity by binding to the protein and chelating agents (e.g., EDTA) to prevent metal ion-catalyzed oxidation of cysteine residues. While room-temperature storage (30°C) leads to rapid inactivation of aFGF in physiological buffer alone, several of these aFGF formulations are stable in vitro for at least 3 months at 30°C. Three aFGF topical formulations were examined in an impaired diabetic mouse model and were found to be equally capable of accelerating wound healing.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1018939228201

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Microencapsulation selection for isolation of yeast mutants with increased secretion of Aspergillus awamori glucoamylase (1993)

Wittrup, K. D. ; Weber, A. L. ; Tsai, P.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 42 (1993), S. 351-356

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ISSN: 0006-3592

Keywords: microencapsulation ; selection ; secretion ; yeast ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: We have developed a microencapsulation selection method which allows the rapid and quantitative screening of 〉106 yeast cells for enhanced secretion of Aspergillus awamori glucoamylase. The method provides a 400-fold single-pass enrichment for high-secreting mutants, and can be straightforwardly adapted for application to growth-based selection schemes with other microorganisms and enzymes. © 1993 John Wiley & Sons, Inc.

Additional Material: 2 Ill.