The treatment of enteric bacterial infections using oral bacteriophage therapy can be challenging since the harsh acidic stomach environment renders phages inactive during transit through the gastrointestinal tract. Solid oral dosage forms allowing site-specific gastrointestinal delivery of high doses of phages, e.g., using a pH or enzymatic trigger, would be a game changer for the nascent industry trying to demonstrate the efficacy of phages, including engineered phages for gut microbiome modulation in expensive clinical trials. Spray-drying is a scalable, low-cost process for producing pharmaceutical agents in dry powder form. Encapsulation of a model Salmonella-specific phage (Myoviridae phage Felix O1) was carried out using the process of spray-drying, employing a commercially available Eudragit S100® pH-responsive anionic copolymer composed of methyl methacrylate-co-methacrylic acid formulated with trehalose. Formulation and processing conditions were optimised to improve the survival of phages during spray-drying, and their subsequent protection upon exposure to simulated gastric acidity was demonstrated. Addition of trehalose to the formulation was shown to protect phages from elevated temperatures and desiccation encountered during spray-drying. Direct compression of spray-dried encapsulated phages into tablets was shown to significantly improve phage protection upon exposure to simulated gastric fluid. The results reported here demonstrate the significant potential of spray-dried pH-responsive formulations for oral delivery of bacteriophages targeting gastrointestinal applications.
The research efforts on the development of ideal forward osmosis membranes with high water flux and low reverse salt flux have been devoted in the recent years. In this study, thin film composite polyamide forward osmosis membranes were prepared. The porous polysulfone (PSU), polyphenylsulfone (PPSU), and polyethersulfone (PESU) substrates used in this study were prepared by the phase inversion process, and the active rejection layer was prepared by interfacial polymerization. All the membranes showed highly asymmetric porous structures with a top dense upper layers and finger-like porous substrates with macro voids in the bottom layer. The addition of 3% lithium chloride (LiCl) to the membrane substrates resulted in an increase in both the water flux and reverse salt flux. PSU and PESU showed the highest water flux when the active layer faced the feed solution (AL-FS), while the largest water flux was obtained when the active layer faced the draw solution (AL-DS). For all the membranes, the water flux under the AL-DS orientation was higher than that under the AL-FS orientation.
We report the behaviour of mixtures of fine bronze and glass spheres under sinusoidal vertical vibration. Depending upon the ratio of their diameters and the amplitude and frequency of the vibration, we observe the formation of sharp separation boundaries between glass-rich and bronze-rich phases, the absence of gross convection which would mix these phases, and a number of oscillatory and non-periodic behaviours. These phenomena are related to the differential air damping of the glass and bronze grains, disappearing completely in the absence of air.
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