Microfluidic platform for continuous synthesis of nanoparticles

Nanoparticles of various kind are used in numerous fields of Pharmaceutical and Biomedical Engineering thanks to their unique structural, chemical and physical properties. The common denominator for most high-end applications is the urgent need for nanoparticles with well-defined and uniform properties. For all these applications, particle nucleation and growth control play a significant role due to size and shape-depended properties. Traditionally the batch synthesis method is the most preferred way of nanoparticle preparation for its simplicity and low cost of instrumentation. However, in many instances, it is very challenging to control mixing, heat and mass transport, especially in the case of ultra-fast precipitation reactions and large- volume reaction mixture. This often leads to unwanted batch-to-batch variation in the quality of the product in terms of particle size and shape. Therefore, better methods are necessary to satisfy annually increasing demands for particles having the monodisperse size and regular shape. Nanoparticle synthesis by microfluidic devices has become one of the most explored methods in the last few years. Microfluidic synthesis promises many advantages over batch synthesis. Firstly, a large surface area to volume ratio of microchannels helps to increase mass and heat transfer in the system. Secondly, it provides higher mixing efficiency using smaller reaction volumes than batch methods. Additionally, microfluidic devices are more suitable to work at harsh conditions in comparison to the batch reactors with regards to rapid temperature and pressure changes while using toxic and explosive materials. In this work, the synthesis of silica, silver and magnetite nanoparticles will be discussed using the microfluidic platform. The goal was to compare a standard batch process with the continuous process using microfluidics of nanoparticle synthesis. The properties of synthesized nanoparticles, particle size and morphology, will be analyzed and discussed

Influence of selective deoxyfluorination on the molecular structure of type-2 N-Acetyllactosamine

16 p.-13 fig.-6 tab.-1 graph. abstr.N-Acetyllactosamine is a common saccharide motif found in various biologically active glycans. This motif usually works as a backbone for additional modifications and thus significantly influences glycan conformational behavior and biological activity. In this work, we have investigated the type-2 N-acetyllactosamine scaffold using the complete series of its monodeoxyfluorinated analogs. These glycomimetics have been studied by molecular mechanics, quantum mechanics, X-ray crystallography, and various NMR techniques, which have provided a comprehensive and complete insight into the role of individual hydroxyl groups in the conformational behavior and lipophilicity of N-acetyllactosamine.The financial support from the Czech Science Foundation (grant No. 23-05146S) and from the Ministry of Education, Youth and Sports (grant No. LTC20052) is gratefully acknowledged. Martin Balouch would like to thank Karel Berka (UP Olomouc) for the access to the COSMOTherm software. Vojtech Hamala is grateful for the financial support of the Martina Roeselova\u0301 Memorial Fellowship granted by the IOCB Tech Foundation. Computational resources have been provided by the e-INFRA CZ project (ID: 90254), supported by the Ministry of Education, Youth and Sports of the Czech Republic and by the ELIXIR-CZ project (ID: 90255), part of the international ELIXIR infrastructure. Jesu\u0301s Jime\u0301nez-Barbero, Ana Arda\u0301 and F. Javier Can\u0303ada acknowledge the financial support from Spanish Ministry of Science, Innovation and Universities under grants PID2021-123781OB-C21 and C22.Peer reviewe

Liposomal co-permeation assay reveals unexpected membrane interactions of commonly prescribed drugs

The permeation of small molecules across biological membranes is a crucial process that lies at the essence of life. Permeation is involved not only in the maintenance of homeostasis at the cell level but also in the absorption and biodistribution of pharmacologically active substances throughout the human body. Membranes are formed by phospholipid bilayers that represent an energy barrier for the permeating molecules. Crossing this energy barrier is assumed to be a singular event, and permeation has traditionally been described as a 1st order kinetic process, proportional only to the concentration gradient of the permeating substance. For a given membrane composition, permeability was believed to be a unary property dependent only on the permeating molecule itself. We provide experimental evidence that this long-held view might not be entirely correct. Liposomes were used in co-permeation experiments with a fluorescent probe, where simultaneous permeation of two substances occurred over a single phospholipid bilayer. Using an assay of six commonly prescribed drugs, we have found that the presence of a co-permeant can either enhance or suppress the permeation rate of the probe molecule, often more than two-fold in each direction. This can have significant consequences for the pharmacokinetics and bioavailability of commonly prescribed drugs when used in combination and provide new insight into so-far unexplained drug-drug interactions, as well as changing the perspective on how new drug candidates are evaluated and tested

Abdominal pain with a twist: a rare presentation of acute gastric volvulus

Acute gastric volvulus is a life threatening condition requiring early diagnosis and aggressive management. Diagnosis of gastric volvulus remains a challenge for clinicians due to variable, non-specific clinical presentation, which requires a high level of suspicion. It should be considered in patients presenting with chest pain and/or epigastric pain, especially in the elderly population. Endoscopic de-rotation could be initially attempted as a therapeutic modality especially in patients who cannot undergo surgery. However, surgery remains the main stay of treatment. Delay in diagnosis can lead to complications like mucosal ischemia, necrosis or perforation, shock, which substantially increase the morbidity and mortality

Drug loading to mesoporous silica carriers by solvent evaporation: A comparative study of amorphization capacity and release kinetics

The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of the porous carrier, the loading method, or the attempted mass fraction of the API. At present, there is no established methodology for the rational selection of these parameters. In the present work, we report a systematic comparison of four well-characterised silica carriers and seven APIs loaded by the same solvent evaporation method. In each case, we find the maximum amorphization capacity by x-ray powder diffraction analysis and measure the in vitro drug release kinetics. For a selected case, we also demonstrate the potential for bioavailability enhancement by a permeation essay