5-HT-dependent synaptic plasticity of the prefrontal cortex in postnatal development.

Important functions of the prefrontal cortex (PFC) are established during early life, when neurons exhibit enhanced synaptic plasticity and synaptogenesis. This developmental stage drives the organization of cortical connectivity, responsible for establishing behavioral patterns. Serotonin (5-HT) emerges among the most significant factors that modulate brain activity during postnatal development.

Precipitation Behavior of Highly Soluble Amphiphilic Drugs in Solution: Physical Instability of Drugs in Solution.

Physical instability of aqueous drug solutions, such as precipitation upon storage, has so far been difficult to predict or model. Understanding the molecular basis of such phenomena can help mitigate by influencing the product composition and by providing a mechanistic basis of experimental and in silico investigations. In this study, inconsistent precipitation of a model drug, GNE-01 in aqueous solutions was investigated.

A Mechanistic Understanding of Monoclonal Antibody Interfacial Protection by Hydrolytically Degraded Polysorbate 20 and 80 under IV Bag Conditions.

Purpose: Polysorbates (PS) contain polyoxyethylene (POE) sorbitan/isosorbide fatty acid esters that can partially hydrolyze over time in liquid drug products to generate degradants and a remaining intact PS fraction with a modified ester distribution. The degradants are composed of free fatty acids (FFAs) --primarily lauric acid for PS20 and oleic acid for PS80-- and POE head groups. We previously demonstrated that under IV bag agitation conditions, mAb1 (a surface-active IgG4) aggregation increased with increasing amounts of degradants for PS20 but not for PS80.

A Comprehensive Assessment of All-Oleate Polysorbate 80: Free Fatty Acid Particle Formation, Interfacial Protection and Oxidative Degradation.

Purpose: Enzymatic polysorbate (PS) degradation and resulting free fatty acid (FFA) particles are detrimental to biopharmaceutical drug product (DP) stability. Different types and grades of polysorbate have varying propensity to form FFA particles. This work evaluates the homogenous all-oleate (AO) PS80 alongside heterogeneous PS20 and PS80 grades in terms its propensity to form FFA particles and other important attributes like interfacial protection and oxidation susceptibility.

Adsorption and Aggregation of Monoclonal Antibodies at Silicone Oil-Water Interfaces.

Monoclonal antibody (mAb) therapies are rapidly growing for the treatment of various diseases like cancer and autoimmune disorders. Many mAb drug products are sold as prefilled syringes and vials with liquid formulations. Typically, the walls of prefilled syringes are coated with silicone oil to lubricate the surfaces during use.