Instability, stabilization, and formulation of liquid protein pharmaceuticals.

http://wolfson.huji.ac.il/purification/Course92632_2014/Aggregation/MAHLER2009.pdf

Protein aggregation: Pathways, induction factors and analysis

The growth of membrane technology

Regulation of retinal blood flow in health and disease

Publisher Summary In order to be suitable for technological applications, catalysts should be stable under operational conditions for weeks or months. With continuous research it is found that enzymes can be stabilized against thermal inactivation. There are three methods that can be employed in the attempt to make enzymes more thermostable: immobilization, chemical modification, and inclusion of additives. Using these methods, rate constants of thermo inactivation of many enzymes have been reduced by as much as 103–105 times; there are enzymes that even without any stabilization display remarkable thermal resistance. For example, Bacillus stearothemphilus a-amylase retains 90% of its activity after 1 hour at 90°C. It is found that at 100°C in 0.1 N HCI, the halflife of adenylate kinase exceeds 30 minutes. Bacillus lichenifomnis amylase continuously operates at 100–115°C. The aforementioned enzymes are made of the same building blocks as other, far less thermostable enzymes. Developments in protein chemistry and the understanding of thermophily, along with sensible analyses of enzyme thermoinactivation and use of common sense, will undoubtedly lead to many new approaches to stabilization of enzymes at high temperatures.

Stabilization of enzymes against thermal inactivation.

Blood flow and microcirculation

Enzyme inactivation with shearing

Shear effects on enzymes

A glutamic acid producing microorganism (Corynebacterium glutamicum) is entrapped in a polyacrylamide gel. These immobilized microorganisms were used to produce glutamic acid in successive batches of fresh medium. Free microorganisms similarly used produced much less glutamic acid under similar conditions.

Glutamic acid production with gel‐entrapped Corynebacterium glutamicum

Plasma fibrinogen in vitro suffers a loss in clottability due to shearing. From calculation of the mass average shear to which plasma is subjected in the circulation, it is estimated that the half-life of fibrinogen is 4 days. This is in excellent agreement with reports that the half-life of fibrinogen in the circulatory system is 4 to 5 days. Hence shearing may be the mechanism for fibrinogen degradation in the circulatory system.

Stanley E. Charm

Papers

Blood flow and microcirculation

Enzyme inactivation with shearing

Shear effects on enzymes

Glutamic acid production with gel‐entrapped Corynebacterium glutamicum

Shear Degradation of Fibrinogen in the Circulation