During the past few decades, numerous protein-based pharmaceuticals to treat chronic and life-threatening diseases have emerged. The short plasma half-life of therapeutic proteins requests frequent administration, usually via parenteral routes. This short-coming is proposed to be solved by the development of an injectable microparticulate drug delivery system (DDS) where the proteins are encapsulated to control the release of the drugs after administration. One way of preparing a protein DDS is through the interaction of proteins and biocompatible coating materials, where the coating materials hinder the quick degradation and release of the proteins...@en

In this study, we developed a microfluidics method, using a so-called H-cell microfluidics device, for the determination of protein diffusion coefficients at different concentrations, pHs, ionic strengths, and solvent viscosities. Protein transfer takes place in the H-cell channels between two laminarly flowing streams with each containing a different initial protein concentration. The protein diffusion coefficients are calculated based on the measured protein mass transfer, the channel dimensions, and the contact time between the two streams. The diffusion rates of lysozyme, cytochrome c, myoglobin, ovalbumin, bovine serum albumin, and etanercept were investigated. The accuracy of the presented methodology was demonstrated by comparing the measured diffusion coefficients with literature values measured under similar solvent conditions using other techniques. At low pH and ionic strength, the measured lysozyme diffusion coefficient increased with the protein concentration gradient, suggesting stronger and more frequent intermolecular interactions. At comparable concentration gradients, the measured lysozyme diffusion coefficient decreased drastically as a function of increasing ionic strength (from zero onwards) and increasing medium viscosity. Additionally, a particle tracing numerical simulation was performed to achieve a better understanding of the macromolecular displacement in the H-cell microchannels. It was found that particle transfer between the two channels tends to speed up at low ionic strength and high concentration gradient. This confirms the corresponding experimental observation of protein diffusion measured via the H-cell microfluidics.

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Here we propose a 3D-molecular structural model for dextran sulphate sodium (DSS) in a neutral aqueous environment based on the results of a molecular modelling study. The DSS structure is dominated by the stereochemistry of the 1,6-linked α-glucose units and the presence of two sulphate groups on each α-glucose unit. The structure of DSS can be best described as a helix with various patterns of di-sulphate substitution on the glucose rings. The presence of a side chain does not alter the 3D-structure of the linear main chain much, but affects the overall spatial dimension of the polymer. The simulated polymers have a diameter similar to or in some cases even larger than model α-hemolysin nano-pores for macromolecule transport in many biological processes, indicating a size-limited translocation through such pores. All results of the molecular modelling study are in line with previously reported experimental data. This study establishes the three-dimensional structure of DSS and summarizes the spatial dimension of the polymer, serving as the basis for a better understanding on the molecular level of DSS-involved electrostatic interaction processes with biological components like proteins and cell pores.@en

The aim of this study was to develop a supercritical carbon dioxide (scCO₂) spray process to coat solid protein particles with a hydrophilic polymer. The final purpose is to manufacture drug particles exhibiting controlled release behaviour in patients. Lysozyme microparticles (about 20 μm) were suspended in a vessel into which a dextran sulphate (DS) solution was dispersed by scCO₂ via a nozzle. Upon interaction with the droplets, DS was deposited onto or mixed with suspended lysozyme particles. Particles of about 100 μm were obtained. The zeta-potential analysis and elemental analysis indicated that the top layer of the particles consisted of both lysozyme and DS. Some of the produced particulate materials showed retarded lysozyme release when exposed to water or phosphate buffered saline, holding promise for future production of controlled drug delivery systems for therapeutic proteins.

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