![]() ![]() Studies reveal that formation of HMWs not only results in a significant loss of biological activity and efficacy but can also potentially lead to toxicity and adverse immunogenic reactions post patient administration, raising questions about product safety ( 4– 6). Aggregation, i.e., formation of high molecular weight species (HMWs) of IgG therapeutic proteins, is widely considered to be a critical quality attribute (CQA)( 3). ![]() ![]() Clinical application necessitates development of stable formulations, as these proteins are susceptible to various degradation pathways including the propensity of mAbs to aggregate at high concentration, elevated temperatures, and varying pH ( 2). Our data support the prospect of using these osmolytes as successful excipients for mAb formulations.Ī majority of the marketed biotherapeutics used to treat life-threatening diseases, such as cancer and immune disorders, are monoclonal antibodies (mAbs) owing to their binding with high specificity to their targets ( 1). Sarcosine emerged as the most successful osmolyte rendering highest degree of protection against aggregation. Our results rank the osmolytes’ stabilizing trend to be sarcosine > betaine > hydroxyectoine > ectoine. No significant impact of osmolyte addition was observed on protein structure, on comparative Fc receptor (FcRn) binding, and on biocompatibility as per our hemolytic assay. A variety of analytical tools have been used for monitoring the impact, dynamic light scattering (DLS) for colloidal stability, Fourier transform infrared (FTIR) spectroscopy and fluorescence spectroscopy for conformational stability and the higher order structure (HOS), and differential scanning calorimetry (DSC) for thermal stability. Experimentation has been performed on two IgG1 mAbs via accelerated stability studies. In this paper, we explore potential use of naturally occurring osmolytes such as betaine, sarcosine, ectoine, and hydroxyectoine for reducing aggregation of mAb therapeutics. Osmolytes such as trehalose, sucrose, and glycine are widely used. One of the most commonly used strategy to overcome protein aggregation is addition of excipients to the formulation. Monoclonal antibodies (mAbs), while incredibly successful, are prone to a variety of degradation pathways, the most significant of which is aggregation. ![]()
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