Modulation of gel formation and drug-release characteristics of lidocaine-loaded poly(vinyl alcohol)-tetraborate hydrogel systems using scavenger polyol sugars

Polyol sugars, displaying a plurality Of hydroxyl groups, were shown to modulate tetra hydroxyborate (borate) cross-linking in lidocaine hydrochloride containing poly(vinyl alcohol) scini-solid hydrogels. Without polyol, demixing of borate cross-linked PVA hydrogels into two distinct phases was noticeable upon lidocaine hydrochloride addition, preventing further use as a topical System. D-Mannitol incorporation was found to be particularly suitable in cicumventing network constriction induced by ionic and pH effects upon adding the hydrochloride salt of lidocaine. A test formulation (4% w/v lidocaine HCl, 2% W/V D-mannitol, 10% w/v PVA and 2.5%, w/v THB) was shown to constitute an effective delivery system, which was characterised by an initial burst release and a drug release mechanism dependent on temperature, changing from a diffusion-controlled system to one with the properties of a reservoir system. The novel flow properties and innocuous adhesion of PVA-tetrahydroxyborate hydrogels Support their application for drug delivery to exposed epithelial surfaces, Such as lacerated wounds. Furthermore, addition of a polyol, such as mannitol, allows incorporation of soluble salt forms of active therapeutic agents by modulation of cross-linking density. (C) 2008 Elsevier B.V. All rights reserved.

Endothelin 1 Stimulates Ca2+-Sparks and Oscillations in Retinal Arteriolar Myocytes via IP3R and RyR-Dependent Ca2+ Release

PURPOSE:
To investigate endothelin 1 (Et1)-dependent Ca(2+)-signaling at the cellular and subcellular levels in retinal arteriolar myocytes.
METHODS:
Et1 responses were imaged from Fluo-4-loaded smooth muscle in isolated segments of rat retinal arteriole using confocal laser microscopy.
RESULTS:
Basal [Ca(2+)](i), subcellular Ca(2+)-sparks, and cellular Ca(2+)-oscillations were all increased during exposure to Et1 (10 nM). Ca(2+)-spark frequency was also increased by 90% by 10 nM Et1. The increase in oscillation frequency was concentration dependent and was inhibited by the EtA receptor (Et(A)R) blocker BQ123 but not by the EtB receptor antagonist BQ788. Stimulation of Ca(2+)-oscillations by Et1 was inhibited by a phospholipase C blocker (U73122; 10 µM), two inhibitors of inositol 1,4,5-trisphosphate receptors (IP(3)Rs), xestospongin C (10 µM), 2-aminoethoxydiphenyl borate (100 µM), and tetracaine (100 µM), a blocker of ryanodine receptors (RyRs).
CONCLUSIONS:
Et1 stimulates Ca(2+)-sparks and oscillations through Et(A)Rs. The underlying mechanism involves the activation of phospholipase C and both IP(3)Rs and RyRs, suggesting crosstalk between these Ca(2+)-release channels. These findings suggest that phasic Ca(2+)-oscillations play an important role in the smooth muscle response to Et1 within the retinal microvasculature and support an excitatory, proconstrictor role for Ca(2+)-sparks in these vessels.

The electrochemical oxidation of catechol and dopamine on platinum in 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C(2)mim][NTf2]) and 1-Butyl-3-methylimidazolium tetrafluoroborate ([C(4)mim][BF4]): Adsorption effects in ionic liquid voltammetry

The electrochemical oxidation of catechol and dopamine has been studied at a platinum micro-electrode (10 pm diameter) in two room temperature ionic liquids (RTILs): 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C(2)mim][NTf2]) and 1-Butyl-3-methylimidazolium tetrafluoroborate ([C(4)mim][BE4]). For catechol in [C(2)mim][NTf2], an electrochemically quasi-reversible oxidation peak was observed at 1.1 V vs. Pt with a back peak at 0.4 V vs. Pt. This is assigned to the two-electron oxidation of catechol to doubly protonated o-benzoquinone. Double-step chronoamperometry gave a diffusion coefficient for the catechol and the oxidised species which is 3.8 x 10(-11) m(2) s(-1) for both. For catechol in [C(4)mim][BF4], a two-electron oxidation wave was observed at 1.0 V vs. Pt with no back peak. Another peak at less positive potential was also observed at 0.6 V vs. Pt in [C(4)mim][BF4] but not in [C(2)mim][NTf2] which is assigned to the adsorption of electrochemically formed neutral o-benzoquinone on the platinum electrode. The oxidised protonated o-benzoquinone is suggested to be deprotonated by the [BF4](-) anion, but not by the [NTf2](-) anion: hence adsorption of the neutral species at the platinum electrode, not the charged species. For dopamine in both RTILs, two chemically irreversible oxidation peaks were observed at 0.75 V and 1.1 V vs. Pt, and assigned to the oxidation of dopamine to the corresponding semi-quinone and the quinone. Potential-step chronoamperometry was carried out on the oxidation waves of dopamine in [C(2)mim][NTf2] and the diffusion coefficient of species in solution was calculated to be 6.85 x 10(-12) m(2) s(-1) and confirmed that the waves corresponded to one and two electron processes. A third wave was observed at 1.8 V vs. Pt which is attributed to the oxidation of the amine group to a radical cation with likely subsequent follow up chemistry. In [C(4)mim][BF4] a peak at less positive potential was observed for dopamine, similar to catechol which is assigned to the adsorption of the neutral quinone species on the platinum electrode formed by the reaction of the removal of protons from the oxidised dopamine with the [BF4](-) anion. (C) 2009 Elsevier B.V. All rights reserved.

Sustained release of proteins from a modified vaginal ring device

A new vaginal ring technology, the insert vaginal ring (InVR), is presented. The InVR overcomes the current shortfall of conventional vaginal rings (VRs) that are generally ineffectual for the delivery of hydrophilic and/or macromolecular actives, including peptides, proteins and antibodies, due to their poor permeation characteristics in the hydrophobic polymeric elastomers from which VRs are usually fabricated. Release of the model protein BSA from a variety of insert matrices for the InVR is demonstrated, including modified silicone rods, directly compressed tablets and lyophilised gels, which collectively provided controlled release profiles from several hours to beyond 4 weeks. Furthermore, the InVR was shown to deliver over 1 mg of the monoclonal antibody 2F5 from a single device, offering a potential means of protecting women against the transmission of HIV.

The extent of grazing release from epiphytism for Sargassum muticum (Phaeophyceae) within the invaded range

The overall biotic pressure on a newly introduced species may be less than that experienced within its native range, facilitating invasion. The brown alga Sargassum muticum (Yendo) Fensholt is a conspicuous and successful invasive species originally from Japan and China. We compared S. muticum and native macroalgae with respect to the biotic pressures of mesoherbivore grazing and ectocarpoid fouling. In Strangford Lough, Northern Ireland, S. muticum thalli were as heavily overgrown with seasonal blooms of epiphytic algae as native macroalgal species were. The herbivorous amphipod Dexamine spinosa was much more abundant on S. muticum than on any native macroalga. When cultured with this amphipod, S. muticum lost more tissue than three native macroalgae, Saccharina latissima (Linnaeus) Lane et al., Halidrys siliquosa (Linnaeus) Lyngbye and Fucus serratus Linnaeus. Sargassum muticum cultured with both ectocarpoid fouling and amphipods showed a severe impact, consistent with our previous findings of large declines in the density of S. muticum observed in the field during the peak of fouling. Despite being a recent introduction into the macroalgal community in Strangford Lough, S. muticum appears to be under biotic pressure at least equal to that on native species, suggesting that release from grazing and epiphytism does not contribute to the invasiveness of this species in Strangford Lough.

The first WASP public data release

The WASP (wide angle search for planets) project is an exoplanet transit survey that has been automatically taking wide field images since 2004. Two instruments, one in La Palma and the other in South Africa, continually monitor the night sky, building up light curves of millions of unique objects. These light curves are used to search for the characteristics of exoplanetary transits. This first public data release (DR1) of the WASP archive makes available all the light curve data and images from 2004 up to 2008 in both the Northern and Southern hemispheres. A web interface () to the data allows easy access over the Internet. The data set contains 3 631 972 raw images and 17 970 937 light curves. In total the light curves have 119 930 299 362 data points available between them.

Physicochemical characterisation and drug release properties of celecoxib hot melt extruded glass solutions

Formulation of Celecoxib into solid dosage forms is difficult due to the physical properties of the drug powder. However for the first time, this paper reports on the drug delivery characteristics glass solutions of celecoxib and polyvinylpyrrolidone prepared by hot melt extrusion, together with use of supercritical carbon dioxide to achieve a porous structure, in order to achieve a stable and enhanced drug release.

Effect of the incorporation of hydroxy-terminated liquid silicones on the cure characteristics, morphology, and release of a model protein from silicone elastomer-covered rods

Silicone elastomer systems have previously been shown to offer potential for the sustained release of protein therapeutics. However, the general requirement for the incorporation of large amounts of release enhancing solid excipients to achieve therapeutically effective release rates from these otherwise hydrophobic polymer systems can detrimentally affect the viscosity of the precure silicone elastomer mixture and its curing characteristics. The increase in viscosity necessitates the use of higher operating pressures in manufacture, resulting in higher shear stresses that are often detrimental to the structural integrity of the incorporated protein. The addition of liquid silicones increases the initial tan delta value and the tan delta values in the early stages of curing by increasing the liquid character (G '') of the silicone elastomer system and reducing its elastic character (G'), thereby reducing the shear stress placed on the formulation during manufacture and minimizing the potential for protein degradation. However, SEM analysis has demonstrated that if the liquid character of the silicone elastomer is too high, the formulation will be unable to fill the mold during manufacture. This study demonstrates that incorporation of liquid hydroxy-terminated polydimethylsiloxanes into addition-cure silicone elastomer-covered rod formulations can both effectively lower the viscosity of the precured silicone elastomer and enhance the release rate of the model therapeutic protein bovine serum albumin. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011