An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(epsilon-caprolactone)

Additive manufacturing or 3D printing as an umbrella term for various materials processing methods has distinct advantages over many other processing methods, including the ability to generate highly complex shapes and designs. However, the performance of any produced part not only depends on the material used and its shape, but is also critically dependent on its surface properties. Important features, such as wetting or fouling, critically depend mainly on the immediate surface energy. To gain control over the surface chemistry post-processing modifications are generally necessary, since it' s not a feature of additive manufacturing. Here, we report on the use of initiator and catalyst-free photografting and photopolymerization for the hydrophilic modification of microfiber scaffolds obtained from hydrophobic medical-grade poly(epsilon-caprolactone) via melt-electrowriting. Contact angle measurements and Raman spectroscopy confirms the formation of a more hydrophilic coating of poly(2-hydroxyethyl methacrylate). Apart from surface modification, we also observe bulk polymerization, which is expected for this method, and currently limits the controllability of this procedure.Peer reviewe

Monitoring drug release from electrospun fibers using an in situ fiber-optics system

Electrospun fiber mats are currently gaining attention as advanced drug delivery systems. Dissolution testing for such systems is generally performed in small vials by immersing the fiber mats in buffered solutions. Defined aliquots of dissolution medium are withdrawn at predefined time points, and the dissolved drug is quantified. However, this procedure is associated with several drawbacks. The method is not automated, and as such requires manual sampling, which potentially leads to inaccuracies particularly in frequent sampling intervals as required for characterization of rapid drug release. Further, the sheet-like fiber mats tend to partially fold upon contact with the dissolution medium, which may potentially affect the release kinetics and reproducibility of the acquired release data. In this study, we investigated the application of a fully automated fiber-optics based dissolution testing system for in situ monitoring of drug release from electrospun fiber mats. Electrospun poly (vinyl alcohol) fibers loaded with lysozyme were used as a model system. To prevent folding of the fiber mats and ensure a fixed position in the dissolution vessel throughout the experiment, a flexible adapter was developed to allow for the attachment of the fiber mats to the vessel walls. Lysozyme release from the fiber mats was compared with the release from cast films with the same composition. Even though the release processes were rather fast and differences in release kinetics of the two systems were marginal, the fiber-optics based dissolution setup allowed for the successful detection of released protein in both cases. The present study, therefore, highlights the potential for the utilization of fully automated fiber-optics based dissolution testing systems for advanced in situ monitoring of drug release from electrospun fibers

Processing-Induced Disorder in Pharmaceutical Materials

This chapter focuses on the major types of pharmaceutical processing methods that have been widely reported to produce disordered material either intentionally or unintentionally. Milling is one of the most frequently used unit operations used by the pharmaceutical industry for reducing the particle size of solids. Thermal processing techniques are mainly used for controlling or improving the release and the subsequent bioavailability of an active pharmaceutical ingredient (API). Techniques such as melt-mixing, spray-congealing, sintering, melt-granulation, and hot-melt extrusion (HME) have developed and evolved rapidly for large-scale pharmaceutical production. Solvent-evaporation-based methods are important processing techniques for both raw materials, such as crystallization of the raw drug, and formulation manufacturing in the pharmaceutical industry. The chapter discusses the processing that can potentially induce the formation of the disordered state during the manufacture of formulations. The widely used solvent-evaporation-based processing techniques in pharmaceutical formulation production include spray-drying, freeze-drying, film casting, and film coating

Vibrational spectroscopic imaging and live cell video microscopy for studying differentiation of primary human alveolar epithelial cells.

Vukosavljevic B, Hittinger M, Hachmeister H, et al. Vibrational spectroscopic imaging and live cell video microscopy for studying differentiation of primary human alveolar epithelial cells. Journal of Biophotonics. 2019;12(6): e201800052

The bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane.

Gram-negative bacteria possess a unique and complex cell envelope, composed of an inner and outer membrane separated by an intermediate cell wall-containing periplasm. This tripartite structure acts intrinsically as a significant biological barrier, often limiting the permeation of anti-infectives, and so preventing such drugs from reaching their target. Furthermore, identification of the specific permeation-limiting envelope component proves difficult in the case of many anti-infectives, due to the challenges associated with isolation of individual cell envelope structures in bacterial culture. The development of an in vitro permeation model of the Gram-negative inner membrane, prepared by repeated coating of physiologically-relevant phospholipids on Transwell(®) filter inserts, is therefore reported, as a first step in the development of an overall cell envelope model. Characterization and permeability investigations of model compounds as well as anti-infectives confirmed the suitability of the model for quantitative and kinetically-resolved permeability assessment, and additionally confirmed the importance of employing bacteria-specific base materials for more accurate mimicking of the inner membrane lipid composition - both advantages compared to the majority of existing in vitro approaches. Additional incorporation of further elements of the Gram-negative bacterial cell envelope could ultimately facilitate model application as a screening tool in anti-infective drug discovery or formulation development