Stallingsdalgaard0958

During freeze drying of biologics, a highly viscous freeze concentrate (FC) is formed upon the initial freezing due to the crystallisation of ice. Protein stability in this freeze concentrated phase is not yet well understood, but can decide upon the success of the lyophilisation itself. Protein stability may be high below the Tg' as it is typically the case during primary drying but decreases above Tg', e.g. during annealing or during aggressive freeze drying above Tg' in presence of a crystalline bulking agent or, beyond freeze drying, during storage of frozen bulk. Different FCs containing monoclonal antibody, sucrose, histidine or phosphate buffer and sodium chloride were prepared via partial freeze drying and analysed for protein aggregation. No solute crystallisation is visible and the systems are vitrifying during cooling. Increasing sugar or buffer concentration showed positive effects on either melting and aggregation temperature or on protein self-interaction as indicated by A2 values. Protein integrity in the FC was not affected by 1 month storage at temperatures above Tg'. Thus, upconcentration of solutes during freezing does not negatively impact protein stability. Exceeding Tg' during freeze drying e.g. upon annealing or, intentionally or unintentionally, during primary drying does not lead to protein aggregation.Omeprazole (OME) is often used to treat disorders associated with gastric hypersecretion in children but a liquid pediatric formulation of this medicine is not currently available. The aim of this study is to develop OME loaded nanoparticles with a view to the obtention of a liquid pharmaceutical dosage form. Eudragit® RS100 was selected as the skeleton material in the inner core and pH-sensitive Eudragit® L100-55 was used as the outer coating of the nanoparticles prepared by the nanoprecipitation method. Pharmacological activity was evaluated by induction of ethanol ulcers in mice. The OME nanoparticles exhibited mean diameters of 174 nm (±17), polydispersity index of 0.229 (±0.01), zeta potential values of -13 mV (±2.60) and encapsulation efficiency of 68.1%. The in vivo pharmacological assessment showed the ability of nanoparticles to protect mice stomach against ulcer formation. The prepared suspension of OME nanoparticles represents effective therapeutic strategy in a liquid pharmaceutical form with the possibility of pediatric administration.The poor solubility and related low bioavailability are a major concern for a large number of small molecule drugs, both on the market and in development. Several formulation strategies exist to overcome this issue. Among them, particle engineering is of outmost importance. The aim of this work is to present the potential of Spray Flash Evaporation (SFE), a new technology for drug particle engineering. To assess the potential of SFE, we carried out a case study on the nano-crystallization of furosemide, a BCS class IV drug. A thorough characterization of the obtained nanocrystals is presented along with a study of dissolution which highlights the solubility improvement provided by nanocrystals produced via SFE technology. The obtained results show a particle size reduction when compared to the raw material, as well as an increase of the dissolution rate of 4.5-fold.Lipid nanocarriers (LNCs) have been successfully produced by many methods including high pressure homogenization, sonication and microemulsification, but it remains very difficult to produce dispersions with greater than 30% LNCs, volume average particle diameter less than 150 nm, and concentration of drugs useful for topical products. This research is the first to propose and demonstrate extrusion to manufacture highly concentrated drug containing LNC dispersions continuously and economically in a single step. By treating crude emulsions in a twin-screw extruder which has sections for homogenizing, mixing and fast-cooling inside the extruder, lidocaine-loaded LNC dispersions were successfully generated with lipid concentration up to 60% and particle diameters less than 50 nm. Electrical conductivity and birefringence measurements indicate that in the lidocaine system, lamellar microemulsions are intermediate structures and compositions with low lipid concentrations that do not present evidence of lamellar structures fail to give nanoparticles when processed. This paper also presents a new method for measuring kinetics of drug release from nanoparticles based on pH stat titration. Sufficiently precise data from pH stat titration allows determination of rate laws for release occurring on a time scale of minutes versus hours or days. The release rate of lidocaine from extruded 35% lipid nanoparticles was constant (zero order release kinetics) through the first hour (40% of drug release), a valuable property for drug delivery.Upper respiratory tract is the primary site of SARS-CoV-2 replication. this website Releasing of pro and anti-inflammatory mediators plays an important role in the immunopathogenesis of Coronavirus Disease 2019 (COVID-19). The aim of this study was to evaluate the early inflammatory response in upper airway by measuring of IFN-γ, TGF-β1 and RANTES at mRNA level. Forty five SARS-CoV-2 infected patients were enrolled, whose were divided in two groups asymptomatic and symptomatic. Twenty healthy persons, SARS-CoV-2 negative were included as controls. Higher IFN-γ expression was detected in SARS-CoV-2 infected patients in comparison with controls (p = 0.0393). IFN-γ expression was increased in symptomatic patients (p = 0.0405). TGF-β1 and RANTES expressions were lower in SARS-CoV-2 infected patients than controls (p less then 0.0001; p = 0.0011, respectively). A significant correlation between IFN-γ and TGF-β1 was observed in SARS-CoV-2 asymptomatic patients (r = +0.61, p = 0.0014). The findings suggest that imbalance between IFN-γ and TGF-β1 expression could be an impact in clinical expression of SARS-CoV-2 infection.Endoplasmic reticulum (ER) stress associated proteins contribute to the pathogenesis of rheumatoid arthritis (RA) through affecting synoviocyte proliferation and proinflammatory cytokine production. The role of DERL3, an ER-associated degradation component, in joint inflammation of RA was explored. Synovial tissues from RA and osteoarthritis (OA) patients were collected, and in RA synovial tissue, DERL3 showed up-regulation and significantly positive correlation with the expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-1. Immunofluorescence result suggested DERL3 was located in fibroblast-like synoviocytes (FLS). Among different inflammatory stimuli, DERL3 could be up-regulated by TNF-α stimulation in FLS. Under TNF-α stimulation, knocking down DERL3, the expression of IL-6, IL-8, MMP-1, MMP-13 was reduced and the activation of nuclear factor kappa B (NF-κB) signaling pathway was inhibited. In pristane-induced arthritis (PIA) rat model, Derl3 was up-regulated in synovial tissue and disease was attenuated after intraarticular injection of siDerl3.