Influence of pulse characteristics and power density on stratum corneum permeabilization by dielectric barrier discharge

Background: In recent years, the medical use of cold atmospheric plasma has received much attention. Plasma sources can be suited for widely different indications depending on their physical and chemical characteristics. Being interested in the enhancement of drug transport across the skin by plasma treatment, we evaluated three dielectric barrier discharges (DBDs) as to their potential use in permeabilizing human isolated stratum corneum (SC). Methods: Imaging techniques (electrochemical and redox-chemical imaging, fluorescence microscopy), transepithelial electrical resistance measurements and permeation studies were employed to study the permeabilizing effect of different DBD-treatments on SC. Results: Filamentous μs-pulsed DBDs induced robust pore formation in SC. Increasing the power of the μs-pulsed DBD lead to more pronounced pore formation but might increase the risk of undesired side-effects. Plasma permeabilization was much smaller for the ns-pulsed DBD, which left SC samples largely intact. Conclusions: The comparison of different DBDs provided insight into the mechanism of DBD-induced SC permeabilization. It also illustrated the need to tailor electrical characteristics of a DBD to optimize it for a particular treatment modality. For future applications in drug delivery it would be beneficial to monitor the permeabilization during a plasma treatment. General significance: Our results provide mechanistic insight into the potential of an emerging interdisciplinary technology – plasma medicine – as a prospective tool or treatment option. While it might become a safe and pain-free method to enhance skin permeation of drug substances, this is also a mechanism to keep in mind when tailoring plasma sources for other uses

Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models.

The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles (SLN) for human lung as a suitable drug delivery system (DDS). Therefore we used a human alveolar epithelial cell line (A549) and murine precision-cut lung slices (PCLS) to estimate the tolerable doses of these particles for lung cells. A549 cells (in vitro) and precision-cut lung slices (ex vivo) were incubated with SLN20 (20% phospholipids in the lipid matrix of the particles) and SLN50 (50% phospholipids in the lipid matrix of the particles) in increasing concentrations. The cytotoxic effects of SLN were evaluated in vitro by lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vitality of lung slices was controlled by staining with calcein AM/ethidium homodimer 1 using confocal laser scanning microscopy and followed by quantitative image analysis with IMARIS software. A549 cell line revealed a middle effective concentration (EC(50)) for MTT assay for SLN20 of 4080 microg/ml and for SLN50 of 1520 microg/ml. The cytotoxicity in terms of LDH release showed comparable EC(50) values of 3431 microg/ml and 1253 microg/ml for SLN20 and SLN50, respectively. However, in PCLS we determined only SLN50 cytotoxic values with a concentration of 1500 microg/ml. The lung slices seem to be a more sensitive test system. SLN20 showed lower toxic values in all test systems. Therefore we conclude that SLN20 could be used as a suitable DDS for the lung, from a toxicological point of view