Some observations on the effects of bioprocessing on biopolymer stability.

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 × 10(6) g/mol.