The Characterization, Stabilization, and Formulation of Acidic Fibroblast Growth Factor

Volkin, David B.; Middaugh, C. Russell

doi:10.1007/0-306-47452-2_3

Cited by 14 publications

(15 citation statements)

References 52 publications

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“…Also, specific ligands that increase protein physical stability (e.g., by increasing the free energy of unfolding) should be investigated. The stabilizing effects of heparin and other polyanions on growth factors (e.g., Chen et al, 1994;Volkin and Middaugh, 1996) and calcium on DNase (Chen et al, 1999) provide good examples. As will be described below, increasing the free energy of unfolding directly correlates with increased resistance of proteins to denaturation during freezing.…”

Section: Specific Ligands/ph That Optimizes Thermodynamic Stability Omentioning

confidence: 99%

“…Unacceptable denaturation and aggregation can be induced readily by the numerous stresses to which a protein in aqueous solution is sensitive; e.g., heating, agitation, freezing, pH changes, and exposure to interfaces or denaturants (Arakawa et aI., 1993;Cleland et aI., 1993;Brange, 2000;Bummer and Koppenol, 2000). Furthermore, even under conditions that thermodynamically greatly favor the native state of proteins, aggregation can arise during months of storage in aqueous solution (e.g., Gu et aI., 1991;Arakawa et aI., 1993;Chen et aI., 1994;Volkin and Middaugh, 1996;Chang et aI., 1996a). In addition, several chemical degradation pathways (e.g., hydrolysis and deamidation) are mediated by water.…”

Section: Introductionmentioning

confidence: 96%

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Rational Design of Stable Lyophilized Protein Formulations: Theory and Practice

Carpenter

Chang

Garzon-Rodriguez

et al. 2002

Pharmaceutical Biotechnology

418

479

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Section: Specific Ligands/ph That Optimizes Thermodynamic Stability Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Rational Design of Stable Lyophilized Protein Formulations: Theory and Practice

Carpenter

Chang

Garzon-Rodriguez

et al. 2002

Pharmaceutical Biotechnology

418

479

View full text Add to dashboard Cite

“…169,372,373 Many formulation excipients have been used and have been found to be very effective in inhibiting protein aggregation during freeze -drying, especially sugars. These excipients include sucrose for rhIL -1ra, 237 both trehalose and sucrose for IL -6 374 and human factor XIII, 375 mannitol for a botulinum neurotoxin, 159 Tween 80 for bovine IgG 368 and rhIL -1ra, 237 Tween 20 and hydroxyethyl starch for a botulinum neurotoxin, 159 hydroxyethyl cellulose for aFGF, 376 and PEG for human FXIII. 375 Stabilization of protein by polymers is likely due to their capability of forming a glass with a higher transition temperature.…”

Section: Freeze -Dryingmentioning

confidence: 99%

External Factors Affecting Protein Aggregation

Wang

Speaker

2010

Aggregation of Therapeutic Proteins

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The behavior of biotherapeutic proteins is signifi cantly different from small molecule drugs both in liquid and solid states, especially in terms of physical stability. One such property is the high tendency of protein molecules to aggregate under a variety of conditions. The aggregation tendency is arguably the most common and troubling manifestation of protein instability during the development of protein biotherapeutics. 1 Protein aggregates usually exhibit either reduced or, in many cases, no biological activity. 2 -5 A clear correlation was established between loss of recombinant factor VIII (rFVIII ) and its degree of aggregation as shown in Fig. 4.1 . 6 To achieve effective prevention or inhibition of protein aggregation, it is of paramount importance to understand all the possible factors that affect or control the protein aggregation process.Many factors have been identifi ed and reported in the literature affecting the process and rate of protein aggregation. These factors can be roughly divided into two major categories: internal (protein structure related) and external (protein environment related). Chapter 3 in this book has focused extensively on factors that belong to the fi rst category. This chapter focuses on the external factors that affect the process and rate of protein aggregation. To facilitate discussion, these external factors are further divided into the following sections: (1) temperature; (2) solution conditions and composition (pH, buffer type and concentration, ionic strength, excipients and level, protein concentration, metal ions, denaturing and reducing agents, impurities, organic solvents, containers/closures, sources of proteins, sample treatment, and analytical methodologies); (3) processing steps (fermentation/expression,

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“…Over the past two decades, topical formulations of growth factors, such as basic and acidic fibroblast growth factors (FGF) (1)(2)(3), epidermal growth factor (4,5), rhVEGF (6), insulin-like growth factor (7), and transforming growth factor-β (8), have been explored for their potential applications in wound healing. Various material, such as alginate (6), gelatin (2), fibrin (7), polyethylene glycol diacrylate (9), polylactic and glycolic acid microspheres (10), polyvinyl alcohol (11), and collagen (12), have been included in these topical formulations.…”

Section: Introductionmentioning

confidence: 99%