Insulin fibrillation under physicochemical parameters of bioprocessing and intervention by peptides and surface-active agents.

IF 8.1 2区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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.

生物加工理化参数下的胰岛素纤维化以及肽和表面活性物质的干预。
即使在胰岛素发现一百周年庆典之后,胰岛素的聚集问题仍然普遍存在,不仅在反复给药后,而且在工业生产、储存、运输和交付过程中都会出现聚集,严重影响蛋白质的质量、功效和有效性。聚集降低了胰岛素的生物利用度,增加了免疫原性增高的风险,对患者的健康构成威胁,并使胰岛素治疗的黄金成功故事黯然失色。在上游和下游生物加工过程中,由于 pH 值、温度、离子强度、搅拌、剪切力和表面化学性质的变化,胰岛素会受到各种物理化学和机械应力的影响,从而导致胰岛素展开和随后的纤维化。这推动了制药业和学术界的研究,以揭示胰岛素聚集的机理,试图设计出合理的策略来调节这一不良现象。本综述简要介绍了生物加工环境因素对胰岛素稳定性的影响,以及与各种分子间相互作用,特别是疏水作用力和静电作用力的相关性。研究发现了胰岛素的易聚集区域,并将其与压力条件下的生物物理变化联系起来。文中介绍了如何寻找新型添加剂、表面活性剂和生物肽来减缓胰岛素的聚集,从而提高整体结构的稳定性。我们希望这篇综述将有助于解决生物加工过程中遇到的胰岛素聚集的现实挑战,确保胰岛素更安全、稳定,并在全球范围内有效治疗糖尿病。
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来源期刊
Critical Reviews in Biotechnology
Critical Reviews in Biotechnology 工程技术-生物工程与应用微生物
CiteScore
20.80
自引率
1.10%
发文量
71
审稿时长
4.8 months
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.
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