Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis.

Recent studies have shown that cellular levels of polyamines (PAs) are significantly altered in neurodegenerative diseases. Evidence from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress, mitochondrial metabolism, cellular immunity, and ion channel functions. Dysfunction of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative diseases. Therefore, in the current work, evidence was collected to determine the possible associations between cellular levels of PAs, and related enzymes and the development of several neurodegenerative diseases, which could provide a new idea for the treatment of neurodegenerative diseases in the future.

The Effects of Excipients on Freeze-dried Monoclonal Antibody Formulation Degradation and Sub-Visible Particle Formation during Shaking.

PURPOSES: We previously reported an unexpected phenomenon that shaking stress could cause more protein degradation in freeze-dried monoclonal antibody (mAb) formulations than liquid ones (J Pharm Sci, 2022, 2134). The main purposes of the present study were to investigate the effects of shaking stress on protein degradation and sub-visible particle (SbVP) formation in freeze-dried mAb formulations, and to analyze the factors influencing protein degradation during production and transportation. METHODS: The aggregation behavior of mAb-X formulations during production and transportation was simulated by shaking at a rate of 300 rpm at 25°C for 24 h. The contents of particles and monomers were analyzed by micro-flow imaging, dynamic light scattering, size exclusion chromatography, and ultraviolet - visible (UV-Vis) spectroscopy to compare the protective effects of excipients on the aggregation of mAb-X. RESULTS: Shaking stress could cause protein degradation in freeze-dried mAb-X formulations, while surfactant, appropriate pH, polyol mannitol, and high protein concentration could impact SbVP generation. Water content had little effect on freeze-dried protein degradation during shaking, as far as the water content was controlled in the acceptable range as recommended by mainstream pharmacopoeias (i.e., less than 3%). CONCLUSIONS: Shaking stress can reduce the physical stability of freeze-dried mAb formulations, and the addition of surfactants, polyol mannitol, and a high protein concentration have protective effects against the degradation of model mAb formulations induced by shaking stress. The experimental results provide new insight for the development of freeze-dried mAb formulations.