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Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zeta potential of −31.20 ± 1.0 mV. Results of TEM revealed spherical particles in the range of 200 nm. The entrapment efficiency was found to be 94.603 ± 2%. The formulation was found to be physically stable over a 3-week period. Results were suggestive of the fact that both NMITLI118RT+ and its delivery system possess significant neuroprotective activity in cerebral ischemia. The liposomal system largely exhibits better performance over NMITLI118RT+ precisely in the post-treatment group. The present studies could elucidate the successful development of a delivery system for NMITLI118RT+ and demonstrate their beneficial neuro-protective potential in overcoming and reversing the consequences of I/R injury following stroke.

Ein bedeutender Punkt in der Brennstoffzellentechnologie ist der Einsatz von platinhaltigen Elektroden, welche die Brennstoffzellentechnologie zu einer teuren Technologie macht. Zum jetzigen Zeitpunkt werden die katalytischen Schichten in großen Maßstäben als Endlos-Elektroden produziert, was dazu führt, dass die einzelnen Elektroden für die Stacks ausgeschnitten und hierbei viel nicht genutztes Elektrodenmaterial, sprich Abfall entsteht. Dieser kann später recycelt werden, jedoch ist eine 100 %ige Rückgewinnung der eingesetzten Rohstoffe nicht möglich. Die Drucktechnik bietet eine Möglichkeit diese Entstehung von Abfall zu vermeiden. Mittels der verschiedenen Drucktechnologien, wie z. B. Inkjet-, Tief- und Siebdruck ist es möglich Elektroden mit gezielten Geometrien zu fertigen, sprich die Elektrodenschichten werden genau an die Erfordernisse angepasst. Der Aufbau von Multilagen ist präzise möglich und es können MEA´s (Membran-Electrode Assembly) mit scharfen, klar abgegrenzten Kanten erstellt werden. In diesem Paper werden Ergebnisse der Inkjet- und Tiefdrucktechnologie vorgestellt, sowie deren Charakterisierung. Da bereits kleinste Unregelmäßigkeiten in den Elektroden zu einem Ausfall des Systems führen können, werden die katalytischen Schichten mittels Oberflächenprofilometer (Veeko Dektak 150) auf ihre Homogenität untersucht. Darüber hinaus werden die Leitfähigkeiten (SÜSS Microtec PM5 Probe System) und die Haftung der gedruckten Schichten in Abhängigkeit von der Drucktechnologie betrachtet. An important point in fuel cell technology is the use of platinum-containing electrodes, which makes fuel cell technology an expensive technology. At present, the catalytic layers are produced on a large scale as continuous electrodes, which results in the individual electrodes being cut out for the stacks, resulting in a lot of unused electrode material, i.e. waste. This can be recycled later, but 100 % recovery of the raw materials used is not possible. The printing technology offers a possibility to avoid this generation of waste. Using the various printing technologies, such as inkjet, gravure, and screen printing, it is possible to produce electrodes with specific geometries, i.e. the electrode layers are precisely adapted to the requirements. The construction of multilayers is precisely possible and MEA's (Membrane Electrode Assembly) with sharp, clearly defined edges can be created. This paper presents the results of inkjet and gravure printing technology and their characterization. Since even the smallest irregularities in the electrodes can lead to system failure, the homogeneity of the catalytic layers is examined using a surface profilometer (Veeko Dektak 150). In addition, the conductivities (SUSS Microtec PM5 Probe System) and the adhesion of the printed layers will be examined as a function of the printing technology.

Printing since many years has been a well-known high throughput technology for producing replications of graphic arts entities (texts, images, aesthetics, gloss and physical impressions) over large varieties of substrates which are dedicated for various needful applications like newspapers, magazines, posters, official documents, packages, braille, textiles, decorative articles and many more. Due to the fact, that printing is a liquid-solution based replication process, where basic ink and substrate are needed, it is now not only limited to printing of graphic arts. Whenever an ink is deposited over a defined substrate and the process can be multiplied, it can be termed as printing and once the final product contains a functionality other than graphic arts application, it can be called as “Printed Functionality”. Some examples for printed functionalities can be found in the following fields: A. Printed electronics (using inks having electronic properties); B. Printed micro-fluidics (using inks having polymeric and elastic properties for directive purposes); C. 3-Dimensional printing (using inks containing binding properties for developing three dimensional structures); D. Printed photonics (using inks having self-assembling properties for building-up symmetric micro-structures); E. Printed pyroelectrics (using inks containing thermally flammable properties); F. Printed ceramics (using inks with ceramic particles) and G. Printed optics and functional surfaces (using inks with transparency, absorbency and reflective properties). All these mentioned applications require functional inks which in turn exhibits some physical-chemical properties e.g. particle size, particle loading, fluid’s rheological properties etc. These properties determine the feasibility of the material’s deposition (in this case the functional inks) with a suitable printing technology. The inkjet printing technology among others has several advantages such as contactless deposition processability, digitalization (batch size one & turn-over time zero), user defined customization and adaptation, industrial relevance, minimal ink demand for R&Ds, freedom of substrate regularity and µm-scale print accuracy etc. Some of the imminent players in the inkjet printing technology market are Canon, Kodak, Hewlett Packard, Fujifilm Dimatix, Konica Minolta and XAAR. They provide print solutions from small to industrial scale printheads, printers, equipments and accessories for the realization of huge variety of application ideas. The inkjet is a versatile, but yet matured technology which finds its use in various application areas e.g. home office documentation, large format posters, variable data printing, security printing, textile printing, wallpapers, household articles, curved surfaces like bottles, printing over edible items, printing of elevated surfaces etc. And, hence there are several literatures published which show the use of the inkjet printing technology in the development of products for printed electronics. Some of the common examples are development of passive and active devices e.g. capacitors, resistors, thin-film-transistors, photovoltaics, sensors, circuits like logic gates for electronic switching, device arrays for detection purposes, point of care health applications, energy harvesting applications etc. But, the exploitation of the inkjet technology has not been intense enough to declare the industrial relevance of the technology to be utilized as a fabrication tool in the market. Meanwhile, all the researchers around the globe aim at a single goal, which is the development of “Proof of Concept” devices and applications. Thus, here in this dissertation the implementation of the inkjet printing technology as a digital fabrication tool is exploited to manufacture and up-scale the printed electronic products, which can show an industrial relevance to the commercial market. The main motivation why printed electronics is in great demand (scientific point of view) and has intensely emerged in the last decades, is because of the primary challenges faced in the fabrication process steps of the µ-electronics society. It is know that the classically fabricated µ-electronic products are in the market since long time due to their high reliability, consistent performance and defined applications in circuitry. But, what cannot be ignored is the involved fabrication steps promote several demerits such as the in-flexibility towards the fabrication process, material wastage, in-ability to up-scale into larger areas and huge quantities, and physical rigidity. Some of these mentioned problems are commonly seen e.g. spin coating, chemical vapor-phase deposition, physical vapor-phase deposition, atomic layer deposition and sputtering fabrication technologies. In this present dissertation, on the contrary, the challenges linked with the manufacturing process of the µ-electronic devices using the inkjet technology are focused and attempts are made to counteract them. Some of the foreseen challenges are: A. process workflow adaptation in device manufacturing; B. validation and evaluation of device performance; C. industrializing the inkjet technology (manufacturing µ-electronics in massive quantities); D. evaluating the fabrication yield of printed devices; D. Generating statistics regarding reliability and scalability; and E. demonstrating tolerances in electronic performances. These are definitely the challenges which must be overcome, and these key research points are addressed in the dissertation.

Additional file 1 : Figure S1. Superoxide anion generation in Pyrogallol treated cells. (A) MDA-MB-231 cells were treated with Pyrogallol (10, 20, 50 and 100 μM) for 24 h followed by 30 mins incubation with 10 μM DHE and analyzed for superoxide anion detection using a fluorescence microscope (above). Phase-contrast images of cells after indicated concentration of Pyrogallol treatment (below). Scale bars, 50 μm. (B) MDA-MB-231 cells were treated with 20 μM Pyrogallol for time point as indicated in the figure, and Western blotting was done for mTORC2 specific markers. All data are representative of three independent experiments. Figure S2. Pyrogallol prevents Ras localization to the plasma membrane. MDA-MB-231 cells pre-treated with FTI (Lonafarnib 1 μM) for 4 h followed by stimulation with Pyrogallol (20 μM) for another 24 h. Cells were analyzed for Ras localization by immunofluorescence microscopy. Data are representative of three independent experiments. Figure S3. Evaluation of sequences of peptides. Evaluation of sequences of synthetic peptides identical to the Ras-binding domain (RBD) of mSIN1. Figure S4. Peptide penetration and mutation analysis. (A) Immunofluorescence images of MDA-MB-231 cells treated with FITC-conjugated P4 (50 μg/ml) for 24 h. (B) RBD sequences of wild-type and mutant. Two of the amino acid residues Tyr-323(Y323) and Leu-325(L325) within the region corresponding to P4 in the wild-type RBD, were conserved across the species. The conserved amino acids tyrosine and leucine were mutated with alanine substitutions. Figure S5. Quantification of data of Fig. 1b Densitometric quantification of protein phosphorylation of mTORC2 specific markers by Western blot data (represented in Fig. 1b). **P ≤ 0.01, ***P ≤ 0.001. Figure S6. Quantification of data of Fig. 2c, d, and e. (A) Densitometric quantification of protein phosphorylation of mTORC2 specific markers by Western blot data (represented in Fig. 2c). (B) Densitometric quantification of protein phosphorylation of mTORC2 specific markers by Western blot data (represented in Fig. 2d). (C) Densitometric quantification of protein phosphorylation of mTORC2 specific markers by Western blot data (represented in Fig. 2e). Pyr (Pyrogallol) ns (not significant). *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. Figure S7. Quantification of data of Fig. 3a and f. (A) Densitometric quantification of protein phosphorylation of mTORC2 specific markers by Western blot data represented in Fig. 3a. (B) Densitometric quantification of Western blot data represented in Fig. 3f. VC (Vehicle control), Pyr (Pyrogallol), and ns, not significant. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. Figure S8. Quantification of data of Fig. 4b and c. Densitometric quantification of protein phosphorylation of mTORC2 specific markers by Western blot data (represented in Fig. 4b). ns, not significant. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.