Some observations on the effects of bioprocessing on biopolymer stability

Abstract

A short review is given of some of the effects of the stresses encountered during bioprocessing of protein and carbohydrate-based macromolecular systems. This is of relevance to the effectiveness and safety of protein or peptide drugs themselves (such as insulin and monoclonal antibodies) and for the integrity of delivery systems (such as various carbohydrate-based hydrogel or mucoadhesive polymers). Some carbohydrate polymers are themselves bioactive or immunostimulatory and particular use is being made of polysaccharide and glycoconjugate vaccines whose effectiveness can be severely effected by chain degradation. Stability criteria include molecular weight and conformation and techniques ranging from simple viscomery measurements to sophisticated analytical ultracentrifuge and multi-angle light scattering coupled to size exclusion chromatography and precision viscometry measurements have been useful in this regard. We focus on some recent work on the degradation and aggregation of immunoglobulin G4-based monoclonal antibodies in response to repeated freezing and thawing and long-term storage, looking at the possible connection between conformation change and aggregation, the effects of storage conditions on the stability of chitosan mucoadhesive systems used for nasal and oral delivery. We look at the effects of sterilization conditions (thermal and irradiation) on the stability of a variety of other polysaccharides such as starches, κ-carrageenan, carboxymethylcellulose, alginate, low- and high-methoxy pectins, guar, and xyloglucans and consider the use of a relatively new method for the evaluation of the molecular weight distribution of glycoconjugate vaccines with molecular weights as high as 100 × 10⁶ g/mol.

Keywords::

• Aggregation
• degradation
• antibodies
• polysaccharides
• storage
• freeze-thaw
• thermal
• irradiation.

Acknowledgements

The author acknowledges the help and assistance of colleagues over the past two decades spanning the time when much of the contributions from the Sutton Bonington laboratory to this field were undertaken, and in particular Professors John Mitchell, Simon Ross-Murphy, and Lisbeth Illum, Drs. Conny Jumel, Neil Errington, Matthew Deacon, Morag Anderson, Immo Fiebrig, Gordon Morris, Trushar Patel, Yanling Lu, Brendan Fish, Sandrine Mulot, Bryan Smith, Ken Davis, Monica Fee, and Ms. Alison Turner. A special thanks to Professor Bob Davis who introduced the author, then a recent appointee under the UK Government New Blood Lecturer scheme to the wonderful possibilities that polysaccharides offer away from their traditional use in the paper and printing industries and in foods, and in particular, the intriguing challenges they have offered—and continue to offer—biophysical science.

Declaration of interest

There are no conflicts of interest.