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Apr 13, 2020

ACS Spring 2020 National Meeting & Expo

Intravenous immunoglobulin aggregation induced by cavitation resulting from mechanical shock: Effect of surface wettability

Cavitation

Protein Aggregation

Protein Adsorption

Abstract

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17

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Abstract

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Keywords

Cavitation

Protein Aggregation

Protein Adsorption

Abstract

Despite the significant clinical benefits of therapeutic proteins, the existence of aggregation-prone regions in most of the proteins’ sequences often results in nucleation of protein aggregation. The protein aggregation provokes adverse immune responses and anaphylaxis in patients and typically can be formed via the conformational changes due to different stress conditions. Such stresses include elevated temperature, surface adsorption, increased ionic strength, low pH, etc. In addition to the environmental factors, the protein aggregation may also arise from cavitation events which can occur during protein formulation administration and transportation. In this study, we investigated the effect of cavitation (induced by mechanical shock) on the stability of Intravenous Immunoglobulin (IVIG), as a model therapeutic protein. In addition, the effect of surface wettability (glass vials functionalized with hydrophobic and hydrophilic surface chemistries) on protein aggregation and particulates formation of IVIG was studied. To monitor the cavitation events and bubble collapsing in vials containing the IVIG formulation, a high-speed camera was used following the application of controlled mechanical shock using a shock test tower. The mechanically-shocked IVIG formulations were analyzed for aggregation using fluorescent-based assay (Bis-ANS; fluorescent probe for nonpolar cavities in proteins) and size exclusion chromatography and for particle formation using microflow imaging (FlowCam). The protein adsorption on surfaces was also quantified by high-performance liquid chromatography. The results indicated that when containers of liquid protein formulations experience mechanical shock, cavitation occurs followed by bubble collapsing and microjets impinging the surfaces, which leads to particle formation. Further, the hydrophilic surface chemistry resulted in lower protein adsorption and lower protein aggregation and particulate formation compared to hydrophobic surface chemistry which enhanced the protein adsorption and aggregation. We envision the understanding gained through this work can lead to developing new interfacial coatings and chemistries that can prevent the mechanical shock-induced formation of particulates in protein solutions.<br/>

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© Copyright 2019 Morressier GmbH.
All rights reserved.