Solid lipid nanoparticles (SLNs) can enhance drug penetration into the skin, yet the mechanism of the improved transport is not known in full. To unravel the influence of the drug-particle interaction on penetration enhancement, 3 glucocorticoids (GCs), prednisolone (PD), the diester prednicarbate (PC) and the monoester betamethasone 17-valerate (BMV), varying in structure and lipophilicity, were loaded onto SLNs. Theoretical permeability coefficients (cm/s) of the agents rank BMV (–6.38) ≧ PC (–6.57) > PD (–7.30). GC-particle interaction, drug release and skin penetration were investigated including a conventional oil-in-water cream for reference. Both with SLN and cream, PD release was clearly superior to PC release which exceeded BMV release. With the cream, the rank order did not change when studying skin penetration, and skin penetration is thus predominantly influenced by drug release. Yet, the penetration profile for the GCs loaded onto SLNs completely changed, and differences between the steroids were almost lost. Thus, SLNs influence skin penetration by an intrinsic mechanism linked to a specific interaction of the drug-carrier complex and the skin surface, which becomes possible by the lipid nature and nanosize of the carrier and appears not to be derived by testing drug release. Interestingly, PC and PD uptake from SLN even resulted in epidermal targeting. Thus, SLNs are not only able to improve skin penetration of topically applied drugs, but may also be of particular interest when specifically aiming to influence epidermal dysfunction.

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Bioprinting for tissue or disease models is a promising but complex process involving biofabrication, cell culture and a carrier material known as bioink. The native extracellular matrix (ECM), which forms the scaffold for cells in vivo, consists of several components including collagen as a gelling agent to confer mechanical stiffness and provide a substrate for cell attachment. Bioprinting therefore needs an artificial ECM that fulfills the same functions as its natural counterpart during and after the printing process. The combination of bioink materials determines the immune response of the host, cell compatibility and adhesion. Here we evaluate multi-material blending with four pre-selected components using a design of experiments approach. Our exemplary designed hydrogel is highly reproducible for the development of artificial ECM and can be expanded to incorporate additional requirements. The bioink displays shear-thinning behavior and a high zero-shear viscosity, which is essential for the printing process. We assessed the printing behavior of our bioink over a wide range of the key process parameters for extrusion-based bioprinting (temperature, pressure, feed rate, and nozzle geometry). Several processing temperatures were linked by rheological measurements directly to the 3D printing process. The printing results were evaluated using a self-developed categoric strand screening process, varying the feed rate and pressure with a fixed nozzle. Accordingly, nozzles differing in size and shape were evaluated and the interactions between printing pressure and feed rate were characterized separately by applying a modified O-R-O test. We tested the short-term cultivation stability of our bioink to mimic the hypothermic and hyperthermic conditions of the human body. As result we present an expandable concept for bioink development and a highly reproducible and well-characterized procedure for printing with the newly developed hydrogel. We provide detailed insights into the relationship between printing parameters, rheological parameters and short-term cultivation stability.