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Solvated lithium closo-dodecaborate, Li2B12H12 with tetrahydrofuran and acetonitrile, show unexpected melting below 150 °C. This feature has been explored to melt-infiltrate Li2B12H12 in a nanoporous SiO2 scaffold. The ionic conductivity of Li2B12H12·xACN reaches 0.08 mS cm-1 in the liquid state at 150 °C making them suitable as battery electrolytes.

When we administered orally a mixture of the anti-diabetic drug, gliclazide (G) and a primary bile acid, they exerted a hypoglycemic effect in a rat model of type 1 diabetes (T1D), but stability of mixture was limited. We aimed to develop and characterize microcapsules incorporating G with a microcapsule-stabilizing bile acid, ursodeoxycholic acid (UDCA). Sodium alginate (SA)-based microcapsules were prepared with either G or G with UDCA and analyzed in terms of morphological, physico-chemical, and electro-chemical characteristics at different pH and temperatures. The microcapsules' effects on viability on muscle cell line (C2C12) and on diabetic rats' blood glucose levels and inflammatory profiles were also examined. Bile acid-based microcapsules maintained their morphology, showed good stability, and compatibility profiles, and the incorporation of UDCA resulted in less G content per microcapsule (p

Gliclazide (G) is a commonly prescribed drug for Type 2 diabetes (T2D). In a recent study, we found that when G was combined with a primary bile acid, and gavaged to an animal model of Type 1 diabetes (T1D), it exerted a hypoglycemic effect. We hypothesized this to be due to metabolic activation of the primary bile acid into a secondary or a tertiary bile acid, which enhanced G solubility and absorption. The tertiary bile acid, taurocholic acid (TCA), has shown strong permeation-enhancing effects in vivo. Thus, we aimed to design, characterize, and test microcapsules incorporating G and TCA in an animal model of T1D.Microcapsules were prepared using the polymer sodium alginate (SA). G-SA microcapsules (control) and G-TCA-SA microcapsules (test) were extensively examined (in-vitro) at different pH and temperatures. The microcapsules were gavaged to diabetic rats, and blood glucose and G concentrations in serum were examined. Ex-vivo studies were also performed using a muscle cell line (C2C12), and cell viability and glucose intake post-treatment were examined.G-TCA-SA microcapsules showed good stability, uniformity, and thermal and chemical excipient compatibilities. TCA did not change the size or the shape of the microcapsules, but it enhanced their mechanical resistance and reduced their swelling properties. G-TCA-SA enhanced the viability of C2C12 cells over 24 hours, and exerted a hypoglycemic effect in alloxan-induced type-1 diabetic rats.The incorporation of TCA into G-microcapsules resulted in functionally improved microcapsules with a positive effect on cell viability and glycemic control in Type-1 diabetic animals.

Gliclazide (G) is used to treat type 2 diabetes (T2D), and also has anti-platelet, anti-radical, and anti-inflammatory effects. G has poor water solubility and high inter-individual variations in absorption, limiting its application in type 1 diabetes (T1D). The bile acid, chenodeoxycholic acid (CDCA), has permeation-enhancing effects. Sodium alginate (SA) was used to microencapsulate G and CDCA to produce control (G-SA) and test (G-CDCA-SA) microcapsules. Both microcapsules showed uniform structure, morphology, and good stability profiles. CDCA reduced G-release at pH 7.8, while G-release was negligible at lower pH values in both microcapsules. CDCA incorporation resulted in less swelling and stronger microcapsules, suggesting improved stability.

We have demonstrated a permeation-enhancing effect of deoxycholic acid (DCA), the bile acid, in diabetic rats. In this study, we designed DCA-based microcapsules for the oral delivery of the antilipidemic drug probucol (PB), which has potential antidiabetic effects. We aimed to further characterize these microcapsules and examine their pH-dependent release properties, as well as the effects of DCA on their stability and mechanical strength at various pH and temperature values. Using the polymer sodium alginate (SA), we prepared PB-SA (control) and PB-DCA-SA (test) microcapsules. The microcapsules were examined for drug content, size, surface composition, release, Micro-CT cross-sectional imaging, stability, Zeta potential, mechanical strength, and swelling characteristics at different pH and temperature values. The microencapsulation efficiency and production yield were also examined. The addition of DCA resulted in microcapsules with a greater density and with reduced swelling at a pH of 7.8 and at temperatures of 25°C and 37°C (p < 0.01). The size, surface composition, production yield, and microencapsulation efficiency of the microcapsules remained similar after DCA addition. PB-SA microcapsules produced multiphasic PB release, while PB-DCA-SA microcapsules produced monophasic PB release, suggesting more controlled PB release in the presence of DCA. The PB-DCA-SA microcapsules showed good stability and a pH-sensitive uniphasic release pattern, which may suggest potential applications in the oral delivery of PB in diabetes.

The electrochemical behaviour of single and arrayed nanoscale interfaces between two immiscible electrolyte solutions (single and array nanoITIES) is presented. The interfaces were formed at nanopores fabricated through the focused ion beam (FIB) milling of silicon nitride (SiN) membranes by using nanopores with approximately 30–80 nm radii and with pore-to-pore separations to pore radius ratios in the range of 16–32. Electrochemistry was performed through the interfacial transfer of tetrapropylammonium (TPrA+) across single and array nanoITIES between water and 1,6-dichlorohexane. The ion-transfer limiting current at the single nanoITIES was in excellent agreement with the current predicted by using an inlaid disc interface model. At nanoITIES arrays, experimental currents were lower than predicted for an array of inlaid interfaces, which is attributed to overlapped diffusion zones. As a result, FIB milling offers an attractive strategy to form nanoITIES for diverse investigations.

In previous studies, we have shown that a gliclazide-cholic acid derivative (G-CA) mixture resulted in an enhanced ileal permeation of G (ex vivo). When administered orally to diabetic rats, it brought about a significant hypoglycaemic effect. In this study, we aim to create a novel microencapsulated-formulation of G-CA with uniform and coherent structure that can be further tested in our rat model of type 1 diabetes (T1D). We also aim to examine the effect of CA addition to G microcapsules in the morphology, structure and excipients' compatibility of the newly designed microcapsules.Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Complete characterizations of microcapsules were carried out.The new G-CA-SA formulation is further optimized by the addition of CA exhibiting pseudoplastic-thixotropic rheological characteristics. Bead size remains similar after CA addition, the new microcapsules show no chemical interactions between the excipients and this was supported further by the spectral studies suggesting bead stability.The new microencapsulated-formulation has good and uniform structural properties and may be suitable for oral delivery of antidiabetic-bile acid formulations.

This paper follows on from Beneficiation of Collie fly ash for synthesis of geopolymer: Part 1 – Beneficiation [1] . In Part 1 beneficiation of fly ash was conducted in a three stage procedure using sieving, milling and magnetic separation to improve fly ash homogeneity and reactivity. At each stage of beneficiation the proportion of reactive amorphous material increases resulting in increased reactivity. This increase in reactivity necessitated changes in solids:liquids ratio to maintain a workable geopolymer mixture. The outcomes from this research clearly identifies that different levels of fly ash beneficiation lead to different geopolymer properties which in turn extends the range of applications for which geopolymers can be used. Compressive strength of all samples were 100 MPa or more with sieving producing a 32% increase in strength. The microstructure of geopolymers changed considerably with beneficiation leading to a very unusual interlocked structure for the sample made from non-magnetic, sieved and milled ash. Although one specific fly ash was used the results presented here are applicable to many other fly ashes.

Beneficiation of the fly ash was conducted in a three stage procedure using sieving, milling and magnetic separation to improve fly ash homogeneity and reactivity. Sieving was effective in reducing large carbon particles and free primary quartz content. Most of the carbon was found to be small and finely dispersed throughout the material, making it unfeasible to remove by sieving. Sieving in conjunction with milling increased surface area from 9.83 m 2 /g to 10.7 m 2 /g. Magnetic separation revealed that amorphous iron was not magnetic and the complete removal of crystalline iron phases is not possible without a robust separation technique. The removal of magnetic phases increased the surface area of the sieved and milled fly ash to 12.9 m 2 /g. The proportion of reactive amorphous material increased at each stage of beneficiation, resulting in increased reactivity. The increase in reactivity necessitated changes in solids:liquids ratio in order to maintain a workable geopolymer mixture which will be discussed in Part 2 of this set of papers. The outcomes from this research clearly identifies that different levels of fly ash beneficiation leads to different geopolymer properties, which in turn extend the range of applications for which geopolymers can be used.

Staphylococcus aureus in biofilms is highly resistant to the treatment with antibiotics, to which the planktonic cells are susceptible. This is likely to be due to the biofilm creating a protective barrier that prevents antibiotics from accessing the live pathogens buried in the biofilm. S. aureus biofilms consist of an extracellular matrix comprising, but not limited to, extracellular bacterial DNA (eDNA) and poly-β-1, 6-N-acetyl-d-glucosamine (PNAG). Our study revealed that despite inferiority of dispersin B (an enzyme that degrades PNAG) to DNase I that cleaves eDNA, in dispersing the biofilm of S. aureus, both enzymes were equally efficient in enhancing the antibacterial efficiency of tobramycin, a relatively narrow-spectrum antibiotic against infections caused by gram-positive and gram-negative pathogens, including S. aureus, used in this investigation. However, a combination of these two biofilm-degrading enzymes was found to be significantly less effective in enhancing the antimicrobial efficacy of tobramycin than the individual application of the enzymes. These findings indicate that combinations of different biofilm-degrading enzymes may compromise the antimicrobial efficacy of antibiotics and need to be carefully assessed in vitro before being used for treating medical devices or in pharmaceutical formulations for use in the treatment of chronic ear or respiratory infections.

Acid and alkaline resistance of class F fly ash based geopolymer pastes has been investigated. As prepared geopolymers showed high solubility in both strong alkali and acid solutions. Calcination of the fly ash based geopolymers at 600 °C resulted in a decrease of amorphous component from 63.4 to 61.6 wt.%. However, the solubility of the Al, Si and Fe ions in 14 M NaOH and 18% HCl after 5 days immersion decreased from 1.3 to 16-fold in comparison to as prepared geopolymer samples. Calcination of the geopolymers also resulted in a 30% reduction in compressive strength. Acid and alkali resistance of the geopolymers investigated strongly depends on mineralogical composition change of the calcined geopolymer. Partial crystallisation of non-reacted fly ash particles in the geopolymer decreases its solubility in acid and alkali solutions.

Nanostructured TiSiN coatings were deposited onto a tool steel substrate. The coated samples were then annealed under vacuum at temperatures ranging from 400° to 900°C. Both mechanical properties and residual stresses in the coatings were determined using nanoindentation methods, assisted by finite element analysis. Intrinsic residual stress was found to be dominant in the as-deposited coatings, but decreased with the increased annealing temperature. In contrast, thermal annealing has little impact on either the Young's modulus or hardness of the coatings at temperatures up to 800°C. Grazing incidence X-ray diffraction analysis indicated that stress relaxation occurred in nanocrystalline TiN grains during thermal annealing. Direct subsurface observation, enabled by focused ion beam microscopy, revealed that microstructural characteristics, responsible for both the Young's modulus and hardness of the coatings remained unaffected during thermal annealing. The degradation of mechanical properties for the coatings annealed at 900°C resulted primarily from the formation of a thin, soft titanium oxide layer at the outer surface.

The corrosion resistance of BaZrO3 to molten barium cuprates is controlled by secondary phases, and requires high chemical and phase purity, as well as high density for sustained flux containment. The high sintering temperatures required for solid-state derived powders is a significant obstacle inhibiting more widespread use of high density BaZrO3. We have investigated the use of Cu2+ doping to enable practical sintering temperatures whilst still producing corrosion resistant ceramics. Low levels of copper addition (0.2 wt.% CuO equiv.) produced densities of >97% theoretical using sintering temperatures as low as 1400 °C, as long as the dopant was added after all powder calcination steps, i.e. immediately before forming/sintering. Corrosion resistance at 0.2 wt.% CuO equiv. was equal to un-doped materials fabricated using the same powder processing method.

This study utilized the Seahorse Analyzer to examine the effect of the bile acid ursodeoxycholic acid (UDCA), on the morphology, swelling, stability, and size of novel microencapsulated β-cells, in real-time. UDCA was conjugated with fluorescent compounds, and its partitioning within the microcapsules was examined using confocal microscopy. UDCA produced microcapsules with good morphology, better mechanical strength (p < 0.01), and reduced swelling properties (p < 0.01), but lower cell viability (p < 0.05) and cell count per microcapsule (p < 0.01). UDCA reduced the cells' biochemical activities, mitochondrial respiration, and energy production, post-microencapsulation. This is the first time biological functions of microencapsulated β-cells have been analyzed in real-time.

Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Gerald F Watts,3 Frank Arfuso,4 Hani Al-Salami11Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, 2Faculty of Science and Engineering, Curtin University, 3School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, 4School of Biomedical Science, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, AustraliaAbstract: The authors have previously designed, developed, and characterized a novel microencapsulated formulation as a platform for the targeted delivery of therapeutics in an animal model of type 2 diabetes, using the drug probucol (PB). The aim of this study was to optimize PB microcapsules by incorporating the bile acid deoxycholic acid (DCA), which has good permeation-enhancing properties, and to examine its effect on microcapsules’ morphology, rheology, structural and surface characteristics, and excipients’ chemical and thermal compatibilities. Microencapsulation was carried out using a BÜCHI-based microencapsulating system established in the authors’ laboratory. Using the polymer sodium alginate (SA), two microencapsulated formulations were prepared: PB-SA (control) and PB-DCA-SA (test) at a constant ratio (1:30 and 1:3:30, respectively). Complete characterization of the microcapsules was carried out. The incorporation of DCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained similar to control. In addition, PB-DCA-SA microcapsules showed good excipients’ compatibilities, which were supported by data from differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray studies, suggesting microcapsule stability. Hence, PB-DCA-SA microcapsules have good rheological and compatibility characteristics and may be suitable for the oral delivery of PB in type 2 diabetes.Keywords: artificial cell microencapsulation, diabetes, bile acids, probucol, antioxidant, anti-inflammatory, BÜCHI B390

Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Hesham S Al-Sallami,3 Zhongxiang Fang,4 Trilochan Mukkur,5 Momir Mikov,6,7 Svetlana Golocorbin-Kon,6,7 Marc Fakhoury,8 Frank Arfuso,5 Hani Al-Salami1 1Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia; 2Faculty of Science and Engineering, Curtin University, Perth, WA, Australia; 3School of Pharmacy, University of Otago, Dunedin, New Zealand; 4School of Public Health, Curtin University, Perth, WA, Australia; 5Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, WA, Australia; 6Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; 7Department of Pharmacy, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro; 8Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Abstract: Gliclazide (G) is an antidiabetic drug commonly used in type 2 diabetes. It has extrapancreatic hypoglycemic effects, which makes it a good candidate in type 1 diabetes (T1D). In previous studies, we have shown that a gliclazide-bile acid mixture exerted a hypoglycemic effect in a rat model of T1D. We have also shown that a gliclazide-deoxycholic acid (G-DCA) mixture resulted in better G permeation in vivo, but did not produce a hypoglycemic effect. In this study, we aimed to develop a novel microencapsulated formulation of G-DCA with uniform structure, which has the potential to enhance G pharmacokinetic and pharmacodynamic effects in our rat model of T1D. We also aimed to examine the effect that DCA will have when formulated with our new G microcapsules, in terms of morphology, structure, and excipients' compatibility. Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) at a ratio of 1:30, and G-DCA-SA (test) at a ratio of 1:3:30. Complete characterization of microcapsules was carried out. The new G-DCA-SA formulation was further optimized by the addition of DCA, exhibiting pseudoplastic-thixotropic rheological characteristics. The size of microcapsules remained similar after DCA addition, and these microcapsules showed no chemical interactions between the excipients. This was supported further by the spectral and microscopy studies, suggesting microcapsule stability. The new microencapsulated formulation has good structural properties and may be useful for the oral delivery of G in T1D. Keywords: type 2 diabetes, bile acids, gliclazide, polymer

Introduction In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures. Method Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C. Results The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p

Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Hesham S Al-Sallami,3 Zhongxiang Fang,4 TK Mukkur,5 Momir Mikov,6,7 Svetlana Golocorbin-Kon,6,7 Marc Fakhoury,8 Gerald F Watts,9 Vance Matthews,10 Frank Arfuso,5 Hani Al-Salami1 1Biotechnology and Drug Development Research Laboratory School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, Western Australia, Australia; 2Faculty of Science and Engineering, Curtin University, Perth, Western Australia, Australia; 3School of Pharmacy, University of Otago, Dunedin, New Zealand; 4School of Public Health, Curtin University, Perth, Western Australia, Australia; 5Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, Western Australia, Australia; 6Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia; 7Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Serbia; 8Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; 9School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia; 10Laboratory for Metabolic Dysfunction, UWA Centre for Medical Research, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia Introduction: In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D). Probucol (PB) is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. Method: Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium alginate (SA), empty (control, SA) and loaded (test, PB-SA) microcapsules were prepared at a constant ratio (1:30). Complete characterizations of microcapsules, in terms of morphology, thermal profiles, dispersity, and spectral studies, were carried out in triplicate. Results: PB-SA microcapsules displayed uniform and homogeneous characteristics with an average diameter of 1 mm. The microcapsules exhibited pseudoplastic-thixotropic characteristics and showed no chemical interactions between the ingredients. These data were further supported by differential scanning calorimetric analysis and Fourier transform infrared spectral studies, suggesting microcapsule stability. Conclusion: The new PB-SA microcapsules have good structural properties and may be suitable for the oral delivery of PB in T2D. Further studies are required to examine the clinical efficacy and safety of PB in T2D. Keywords: artificial cell microencapsulation, diabetes, antioxidant, anti-inflammatory, Probucol