Professor Purdue University West Lafayette, Indiana
Abstract: Cryoprotecting proteins in solid matrices containing buffers, sugars, and surfactants is a common process to ensure protein stability in the solid state. Two main factors that influence the stability of a protein include the interaction of the protein with the stabilization matrix, and the mobility of the protein in the matrix. The protein must be intimately mixed with the stabilizing agent, usually a sugar, to maximize the ability of the protein to remain intact during storage. In addition, the sugar matrix should inhibit the mobility of the protein in the matrix to maximize stability. Solid-state NMR spectroscopy has been used to measure each of these parameters, with the SSNMR mobility and phase separation data compared to protein aggregation upon storage as determined by size exclusion data. The SSNMR data correlated with the aggregation data, where the best stability was achieved for homogeneous (no phase separation) formulations with the least mobility.
Learning Objectives:
Understand the current research and development in technologies for stabilizing solid-state biological formulations, such as spray drying and lyophilization of biologics and LNPs.
Highlight advanced experimental biophysical and biochemical characterization techniques for phase separation and mobility in solid biological formulations, focusing on the opportunities and challenges for enhancing stability based upon characterization data.
Understand the molecular mechanisms for the stabilization of solid-state protein formulations, including the rational selection of excipients to improve stability.
