Microarray Patches: Poking a Hole in the Challenges Faced When Delivering Poorly Soluble Drugs

Poorly soluble drugs constitute more than 60% of currently marketed pharmaceuticals with over two-thirds of promising new chemical entities failing to enter a clinical setting due to solubility issues. Although oral formulations have made some impact, alternative enhancement strategies for administration of such molecules are actively sought. Over the last decade, innovation on a global scale has enabled the expansion of the frontiers of microarray patches (MAPs) further than ever before. Initially designed to load low doses of hydrophilic and potent therapeutic agents, MAPs are now becoming a viable strategy for the immediate and long-acting delivery of poorly soluble drugs through the skin. This together with the advantages of transdermal administration over the oral and parenteral routes, make of MAPs an appealing platform for the development of products with increased patient compliance. Undoubtedly, MAPs will soon become a readily available therapeutic alternative, and experts from academia, industry and regulatory bodies are working together aiming to facilitate the progression of MAPs toward safe and effective clinical use. This review aims to highlight the ability of MAPs to deliver poorly soluble actives, discuss the mechanisms behind in-skin drug absorption, and evaluate the future direction of the field.     

Landscape of time and immobility

ABSTRACT

This paper sheds a light on the ephemeral landscape of Palestine. Under a deliberate process of ‘erasing, peeling, cutting and pasting’, the physical and mental maps of Palestine today are rapidly changing with the Palestinians being pushed out of the scene. This colonial project has been best represented by Sari Hanafi as ‘spacio-cidal’ as it targets the landscape and consequently the narrative of those who shape it.

Stemming from the need for an alternative discourse to narrate and redraw the map from a local lens, I use the village of Beit Iksa as an example to portray the spatial restructuring of the landscape. I show how ‘greening’ casts a shadow on the Israeli colonial strategies that lie beneath to alienate and ‘reinvent’ the rural scene. And yet, because for every strategy of control there is a tactic to resist, I show how through spatial interventions, I tried to rethink the rural and challenge its ideological transformation into a void; a leftover landscape shaped by time and immobility and yet is loaded with spatial potentials and open to change.     

Spin injection in n-type resonant tunneling diodes

We have studied the polarized resolved photoluminescence of n-type GaAs/AlAs/GaAlAs resonant tunneling diodes under magnetic field parallel to the tunnel current. Under resonant tunneling conditions, we have observed two emission lines attributed to neutral (X) and negatively charged excitons (X⁻). We have observed a voltage-controlled circular polarization degree from the quantum well emission for both lines, with values up to −88% at 15 T at low voltages which are ascribed to an efficient spin injection from the 2D gases formed at the accumulation layers.     

Why Our Patients Like Daily Hemodialysis

The option of daily hemodialysis (HD) was discussed in November 1998 with a group of 35 HD patients on home or self‐care/limited‐care HD in a single, freestanding unit. After the meeting, 3 patients on home HD chose to switch to daily HD. The clinical success of the first patient and the immediate followers was one of the main reasons for further extension of this experience. At the time of this writing (February 2000), 10 patients were on a daily HD program (8 at home and 2 in a self‐care/limited‐care center) and one was in training for home daily HD. One further patient who tried 1 month of daily HD dropped out for logistic reasons. On daily HD, patients are dialyzed 2 – 3 hours/day, 6 days/ week, with blood flow of 270 – 300 mL/min, on bicarbonate dialysate with individually determined levels of Na and K. The schedule is flexible and a switch to 3 – 4 dialyses/week is occasionally allowed for working needs or for vacation. In addition to the well‐known clinical advantages (better well‐being, blood pressure control, nutrition, etc.), some patients preferred daily HD because of easier organization of daily activities, including work schedule. Patients initially feared frequent needle punctures and excessive burden on partners, but those concerns proved to be less a problem than anticipated. All current patients are willing to continue daily HD; only a nursing shortage limits further extension of the program in the self‐care/limited‐care center.     

Assessing the DNA Damaging Effectiveness of Ionizing Radiation Using Plasmid DNA

Plasmid DNA is useful for investigating the DNA damaging effects of ionizing radiation. In this study, we have explored the feasibility of plasmid DNA-based detectors to assess the DNA damaging effectiveness of two radiotherapy X-ray beam qualities after undergoing return shipment of ~8000 km between two institutions. The detectors consisted of 18 μL of pBR322 DNA enclosed with an aluminum seal in nine cylindrical cavities drilled into polycarbonate blocks. We shipped them to Toronto, Canada for irradiation with either 100 kVpor 6 MV X-ray beams to doses of 10, 20, and 30 Gy in triplicate before being shipped back to San Diego, USA. The Toronto return shipment also included non-irradiated controls and we kept a separate set of controls in San Diego. In San Diego, we quantified DNA single strand breaks (SSBs), double strand breaks (DSBs), and applied Nth and Fpg enzymes to quantify oxidized base damage. The rate of DSBs/Gy/plasmid was 2.8±0.7greater for the 100 kVp than the 6 MV irradiation. The 100 kVp irradiation also resulted in 5±2 times more DSBs/SSB than the 6 MV beam, demonstrating that the detector is sensitive enough to quantify relative DNA damage effectiveness, even after shipment over thousands of kilometers.     

Piezoelectric properties of zinc oxide/iron oxide filled polyvinylidene fluoride nanocomposite fibers

Piezoelectric nanogenerators (PENG) with flexible and simple design have pronounced significance in fabricating sustainable devices for self-powering electronics. This study demonstrates the fabrication of electrospun nanocomposite fibers from polyvinylidene fluoride (PVDF) filled zinc oxide (ZnO)/iron oxide (FeO) nanomaterials. The nanocomposite fiber based flexible PENG shows piezoelectric output voltage of 5.9 V when 3 wt% of ZnO/FeO hybrid nanomaterial is introduced, which is 29.5 times higher than the neat PVDF. No apparent decline in output voltage is observed for almost 2000 s attributed to the outstanding durability. This higher piezoelectric output performance is correlated with the β-phase transformation studies from the Fourier transformation infrared spectroscopy and the crystallinity studies from the differential scanning calorimetry. Both these studies show respective enhancement of 3.79 and 2.16% in the β-phase crystallinity values of PVDF-ZnO/FeO 3 wt% composite. Higher dielectric constant value obtained for the same composite (three times higher than the neat PVDF) confirms the increased energy storage efficiency as well. Thus the proposed soft and flexible PENG is a promising mechanical energy harvester, and its good dielectric properties reveals the ability to use this material as good power sources for wearable and flexible electronic devices.

     

Waste from brewing (trub) as a source of protein for the food industry

The use of agro-industrial waste for food enrichment can be limited, due to taste, odour, colour and other unpleasant characteristics. Trub (brewing waste) has important nutrients, such as proteins and carbohydrates, and phytochemical compounds; however, its applications are hindered by the astringent flavour. In order to reduce the bitterness of trub, aqueous extractions were realized at high temperature (100 °C per 1 h) in five steps. Two fractions were obtained; a liquid fraction (containing bitter compounds) and a solid fraction (the trub after the extraction process; TAP). Both fractions and the trub before the extraction process (TBP) were evaluated. The bitterness of TBP was significantly reduced in TAP while the protein content increased; TAP presented a branched network and changes in its structure. The reduction in bitterness and the high protein content allows the use of trub in the food industry.     

Enhanced utilisation of nonmarketable fish: physical,nutritional and sensory properties of ‘clean label’ fish burgers

Four ‘clean label’ formulations for fish burgers made with mechanically separated fish meat were characterised in sensory, textural and chemical terms. The formulations differed in the ratios of European sea bass to rainbow trout (50:50 and 30:70) and the ratios of fish to potato flakes (dry matter ratio, DMR: 2.5:1 and 1.5:1). The sensory profile was mainly influenced by DMR. Recipes with the higher DMR were positively correlated with sandy, dry and crusty attributes, salty taste and overall flavour. Soft texture was perceived for recipes with the lower DMR, although no differences in texture were detected by a texturometer. Lowering DMR increased ash and water content and decreased protein content, as expected. The results indicated that 100 g of burger provided more essential fatty acids than the recommended daily intake, irrespective of formulation. In conclusion, multiple factor analysis indicated that the main changes detected and perceived were due to DMR.     

Heterogeneous Cubic Multidimensional Integrated Circuit for Water and Food Security in Fish Farming Ponds

Among major food production sectors, world aquaculture shows the highest growth rate, providing more than 50% of the global seafood market. However, water pollution in fish farming ponds is regarded as the leading cause of fish death and financial losses in the market. Here, an Internet of Things system based on a cubic multidimensional integration of circuit (MD‐IC) is demonstrated for water and food security applications in fish farming ponds. Both faces of the silicon substrate are used for thin‐film‐based device fabrication. The devices are interconnected via through‐silicon‐vias, resulting in a bifacial complementary metal‐oxide‐semiconductor‐compatible electronics system. The demonstrated cubic MD‐IC is a complete, small, and lightweight system that can be easily deployed by farmers with no need for specialists. The system integrates on its outer sides simultaneous air and water quality monitoring devices (temperature, electrical conductivity, ammonia, and pH sensors), solar cells for energy‐harvesting, and antenna for real‐time data‐transfer, while data‐management circuitry and a solid‐state battery are integrated on its internal faces. Microfluidic cooling technology is used for thermal management in the MD‐IC. Finally, a biofriendly polymeric encapsulation is used to waterproof the embedded electronics, improve the mechanical robustness, and allow the system to float on the surface of the water.