A Review on Therapeutic Proteins: Stability Aspects and Clinical Implications

Abstract

Therapeutics proteins require protection against several sources of chemical and /or physical instabilities. One such physical instability is the high tendency of protein molecules to aggregate under a wide range of processing and storage conditions. Aggregates of the protein drug may enhance the product's immunogenicity and could compromise its efficacy. There are two major pathways of protein aggregation; these are aggregation of native protein conformations (colloidal instability) or aggregation of partially denatured proteins (non-native protein aggregation). Certain solution conditions, which reduce aggregation through one pathway, may lead to an increase in aggregation through the other pathway; therefore, a logical balanced formulation procedure should be implemented in order to reduce aggregation due to both pathways. For certain protein molecules, optimizing solution conditions might not result in the required reduction in protein aggregation; in this case, alteration in the protein structure might be required. This alteration can be, either in vivo through protein coding gene manipulation or synthetic such as protein PEGylation. There are two aggregation pathways for protein in liquid formulations, aggregation due to conformational stability and aggregation due to colloidal instability. Protein melting temperature (Tm) and time-dependent rate of thermal unfolding can assess conformational stability of a protein while measurement of second virial coefficients from static light scattering or protein precipitation in the presence of a salting out salt such as ammonium sulphate can be used to assess colloidal stability of a protein.

Development and evaluation of culture media based on extracts of the cyanobacterium Arthrospira platensis

“…Technological advancements are continuously needed for a wide range of applications in biotechnological and pharmaceutical industries, such as the production of vaccines ( Plotkin et al, 2017 ), blood and blood components ( Haldar et al, 2019 ), cell lines for cell therapies ( Thakar et al, 2020 ), gene therapies ( Gonçalves and de Paiva, 2017 ; Papanikolaou and Bosio, 2021 ), and recombinant therapeutic proteins ( Dingermann, 2008 ; Qarawi et al, 2019 ). These advancements require new, high-yielding, and cost-effective formulations of culture media based on sources that are sustainable, have a zero or negative carbon footprint, and are preferably vegan, especially if used in the cosmetic industry ( Pathak and Martirosyan, 2012 ; Pathak and Singhal, 2013 ).…”