Non-Arrhenius Protein Aggregation
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 3
Abstract
Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be linked with cytotoxicity and patient immunogenicity. Therefore, investigations of protein aggregation remain a major focus in pharmaceutical companies and academic institutions. Due to the complexity of the aggregation process and temperature-dependent conformational stability, temperature-induced protein aggregation is often non-Arrhenius over even relatively small temperature windows relevant for product development, and this makes low-temperature extrapolation difficult based simply on accelerated stability studies at high temperatures. This review discusses the non-Arrhenius nature of the temperature dependence of protein aggregation, explores possible causes, and considers inherent hurdles for accurately extrapolating aggregation rates from conventional industrial approaches for selecting accelerated conditions and from conventional or more advanced methods of analyzing the resulting rate data.
Authors and Affiliations
Wei Wang, Christopher J. Roberts
Keywords
Related Articles
- EP ID EP681144
- DOI 10.1208/s12248-013-9485-3
- Views 113
- Downloads 0
A Fast Method for Testing Covariates in Population PK/PD Models
The development of covariate models within the population modeling program like NONMEM is generally a time-consuming and non-trivial task. In this study, a fast procedure to approximate the change in objective function v...
How Promiscuous Are Pharmaceutically Relevant Compounds? A Data-Driven Assessment
The online version of this article (doi:10.1208/s12248-012-9421-y) contains supplementary material, which is available to authorized users.
The Use of Modeling Tools to Drive Efficient Oral Product Design
Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active Pharmaceutical Ingredi...
Epidermal Growth Factor Receptor-Targeted Gelatin-Based Engineered Nanocarriers for DNA Delivery and Transfection in Human Pancreatic Cancer Cells
Type B gelatin-based engineered nanocarrier systems (GENS) have been used over the last several years as a non-condensing systemic and oral DNA delivery system. In this study, we have modified the surface of GENS with ep...
Variation of Stratum Corneum Biophysical and Molecular Properties with Anatomic Site
Several serine protease enzymes are known to be involved in both normal desquamation and the inflammatory processes of the skin. Alteration in the activity of these proteases should also affect corneocyte maturity and si...