Chinmaya Panda, Sachin Kumar, Sharad Gupta, Lalit M Pandey
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引用次数: 0
Abstract
Even after the centenary celebration of insulin discovery, there prevail challenges concerning insulin aggregation, not only after repeated administration but also during industrial production, storage, transport, and delivery, significantly impacting protein quality, efficacy, and effectiveness. The aggregation reduces insulin bioavailability, increasing the risk of heightened immunogenicity, posing a threat to patient health, and creating a dent in the golden success story of insulin therapy. Insulin experiences various physicochemical and mechanical stresses due to modulations in pH, temperature, ionic strength, agitation, shear, and surface chemistry, during the upstream and downstream bioprocessing, resulting in insulin unfolding and subsequent fibrillation. This has fueled research in the pharmaceutical industry and academia to unveil the mechanistic insights of insulin aggregation in an attempt to devise rational strategies to regulate this unwanted phenomenon. The present review briefly describes the impacts of environmental factors of bioprocessing on the stability of insulin and correlates with various intermolecular interactions, particularly hydrophobic and electrostatic forces. The aggregation-prone regions of insulin are identified and interrelated with biophysical changes during stress conditions. The quest for novel additives, surface-active agents, and bioderived peptides in decelerating insulin aggregation, which results in overall structural stability, is described. We hope this review will help tackle the real-world challenges of insulin aggregation encountered during bioprocessing, ensuring safer, stable, and globally accessible insulin for efficient management of diabetes.
期刊介绍:
Biotechnological techniques, from fermentation to genetic manipulation, have become increasingly relevant to the food and beverage, fuel production, chemical and pharmaceutical, and waste management industries. Consequently, academic as well as industrial institutions need to keep abreast of the concepts, data, and methodologies evolved by continuing research. This journal provides a forum of critical evaluation of recent and current publications and, periodically, for state-of-the-art reports from various geographic areas around the world. Contributing authors are recognized experts in their fields, and each article is reviewed by an objective expert to ensure accuracy and objectivity of the presentation.