Alternative drying techniques for the manufacturing of hydrogel-forming and dissolving microneedle arrays.

Dissolving polymeric microneedle arrays and hydrogel-forming microneedle arrays have attracted much attention during recent years due mainly to their biocompatibility and capacity for enhanced drug delivery. Nevertheless, for the production of this type of devices, typically, a drying step is required. Microneedles are prepared following a micromoulding technique using aqueous blends of Gantrez® S-97. Currently, production of microneedles arrays involves a long drying process of 48 hours. Therefore alternative drying methods were investigated including microwave radiation and hot air convection.

Organs of the human brain, created by the human hand? The social epistemology of information technology

Purpose
– Information science has been conceptualized as a partly unreflexive response to developments in information and computer technology, and, most powerfully, as part of the gestalt of the computer. The computer was viewed as an historical accident in the original formulation of the gestalt. An alternative, and timely, approach to understanding, and then dissolving, the gestalt would be to address the motivating technology directly, fully recognizing it as a radical human construction. This paper aims to address the issues.

Design/methodology/approach
– The paper adopts a social epistemological perspective and is concerned with collective, rather than primarily individual, ways of knowing.

Findings
– Information technology tends to be received as objectively given, autonomously developing, and causing but not itself caused, by the language of discussions in information science. It has also been characterized as artificial, in the sense of unnatural, and sometimes as threatening. Attitudes to technology are implied, rather than explicit, and can appear weak when articulated, corresponding to collective repression.

Research limitations/implications
– Receiving technology as objectively given has an analogy with the Platonist view of mathematical propositions as discovered, in its exclusion of human activity, opening up the possibility of a comparable critique which insists on human agency.

Originality/value
– Apprehensions of information technology have been raised to consciousness, exposing their limitations.

Rheological characterization of thermoresponsive semisolids for vaginal HIV vaccine delivery

Purpose. To manufacture and characterize, through oscillatory rheology, thermoresponsive rheologically structured vehicles
(RSV’s) capable of enhanced retention times within the vagina for the purposes of HIV vaccine delivery.
Methods. Pluronics F127, F108 and F68 were investigated and RSV’s were prepared by dissolving sorbic acid (0.1% w/w)
and mucoadhesive component (Gantrez SBF97 or Noveon AA1, 3% w/w) in the required amount of H2O and NaOH.
Pluronic (10% w/w) was added via mixing in an ice-bath followed by hydroxyethylcellulose (5%) and subsequently
poly(vinylpyrollidone) (4%w/w). Oscillatory temperature sweeps between 10-38°C were preformed within the linear
viscoelastic region of the formulations on an AR2000 rheometer (T.A. Instruments, Surrey, England) with a 2cm diameter
parallel plate geometry and a plate gap of 1000µm at 1Hz.

Electrooxidation of the iodides [C(4)mim]I, LiI, NaI, KI, RbI, and CsI in the room temperature ionic liquid [C(4)mim][NTf2]

The electrochemical oxidation of 1-butyl-3-methylimidazolium iodide, [C(4)mim]I, has been investigated by cyclic voltammetry at a platinum microelectrode at varying concentrations in the RTIL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(4)mim][NTf2]. Two oxidation peaks were observed. The first peak is assigned to the oxidation of iodide to triiodide, in an overall two-electron process: 3I(-)- 2e(-) -> I-3(-). At higher potentials, the electrogenerated triiodide oxidizes to iodine, in an overall one-electron process: I-3(-) - e(-) -> 3/2I(2). An average diffusion coefficient, D, for I- of 1.55 x 10(-11) m(2) s(-1) was obtained. A digital simulation program was used to simulate the voltammetric response, and kinetic parameters were successfully extracted. The parameters deduced from the simulation include D for I-, I-3(-), and I-2 and K-eq,K-2, the equilibrium constant for the reaction of iodide and iodine to form triiodide. Values for these parameters are of the same order as those previously published for the oxidation of Br- in the same RTIL [Allen et al. J. Electroanal. Chem. 2005, 575, 311]. Next, the cyclic voltammetry of five different inorganic iodide salts was studied by dissolving small amounts of the solid in [C(4)mim][NTf2]. Similar oxidation peaks were observed, revealing diffusion coefficients of ca. 0.55, 1.14, 1.23, 1.44, and 1.33 x 10(-11) m(2) s(-1) and solubilities of 714, 246, 54, 83, and 36 mM for LiI, NaI, KI, RbI, and CsI, respectively. The slightly smaller diffusion coefficients for the XI salts (compared to [C(4)mim]I) may indicate that I- is ion-paired with Li+, Na+, K+, Rb+, and Cs+ in the RTIL medium.

The electrochemical oxidation and reduction of nitrate ions in the room temperature ionic liquid [C(2)mim][NTf2]; the latter behaves as a 'melt' rather than an 'organic solvent'

The electrochemical oxidation of 1-butyl-3-methylimidazolium nitrate [C(4)mim][NO3] was studied by cyclic voltammetry in the room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [C(2)mim][NTf2]. A sharp peak was observed on a Pt microelectrode (d = 10 mu m), and a diffusion coefficient at infinite dilution of ca. 2.0 x 10(-11) m(2) s(-1) was obtained. Next, the cyclic voltammetry of sodium nitrate (NaNO3) and potassium nitrate (KNO3) was studied, by dissolving small amounts of solid into the RTIL [ C2mim][ NTf2]. Similar oxidation peaks were observed, revealing diffusion coefficients of ca. 8.8 and 9.0 x 10(-12) m(2) s(-1) and solubilities of 11.9 and 10.8 mM for NaNO3 and KNO3, respectively. The smaller diffusion coefficients for NaNO3 and KNO3 (compared to [C(4)mim][NO3]) may indicate that NO3- is ion-paired with Na+ or K+. This work may have applications in the electroanalytical determination of nitrate in RTIL solutions. Furthermore, a reduction feature was observed for both NaNO3 and KNO3, with additional anodic peaks indicating the formation of oxides, peroxides, superoxides and nitrites. This behaviour is surprisingly similar to that obtained from melts of NaNO3 and KNO3 at high temperatures ( ca. 350 - 500 degrees C), and this observation could significantly simplify experimental conditions required to investigate these compounds. We then used X-ray photoelectron spectroscopy (XPS) to suggest that disodium( I) oxide (Na2O), which has found use as a storage compound for hydrogen, was deposited on a Pt electrode surface following the reduction of NaNO3.

Lanthanide-doped luminescent ionogels

Ionogels are solid oxide host networks con. ning at a meso-scale ionic liquids, and retaining their liquid nature. Ionogels were obtained by dissolving lanthanide(III) complexes in the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide, [C(6)mim][Tf2N], followed by confinement of the lanthanide-doped ionic liquid mixtures in the pores of a nano-porous silica network. [C(6)mim][Ln(tta)(4)], where tta is 2-thenoyltrifluoroacetonate and Ln = Nd, Sm, Eu, Ho, Er, Yb, and [choline](3)[Tb(dpa)(3)], where dpa = pyridine-2,6-dicarboxylate (dipicolinate), were chosen as the lanthanide complexes. The ionogels are luminescent, ion-conductive inorganic-organic hybrid materials. Depending on the lanthanide(III) ion, emission in the visible or the near-infrared regions of the electromagnetic spectrum was observed. The work presented herein highlights that the confinement did not disturb the first coordination sphere of the lanthanide ions and also showed the excellent luminescence performance of the lanthanide tetrakis beta-diketonate complexes. The crystal structures of the complexes [C(6)mim][Yb(tta)(4)] and [choline](3)[Tb(dpa)(3)] are reported.

Pyrrolidinium Ionic Liquid Crystals

N-Alkyl-N-methylpyrrolidinium cations have been used for the design of ionic liquid crystals, including a new type of uranium-containing metallomesogen. Pyrrolidinium salts with bromide, bis(trifluoromethylsulfonyl)-imide, tetrafluoroborate, hexafluorophosphate, thiocyanate, tetrakis(2-thenoyltrifluoroacetonato)europate(III) and tetrabromouranyl] counteranions were prepared. For the bromide salts and tetrabromouranyl compounds, the chain length of the alkyl group CnH2n+1 was varied from eight to twenty carbon atoms (n =8. 10-20). The compounds show rich mesomorphic behaviour: highly ordered smectic phases (the crystal smectic E phase and the uncommon crystal smectic T phase), smectic A phases, and hexagonal. columnar phases were observed, depending on chain length and anion. This work gives better insight into the nature and formation of the crystal smectic T phase, and the Molecular requirements for the appearance of this highly ordered phase. This uncommon tetragonal mesophase is thoroughly discussed on the basis of detailed powder X-ray diffraction experiments and in relation to the existing literature. Structural models are proposed for self-assembly of the molecules within the smectic layers. In addition, the photophysical properties of the compounds containing a metal complex anion were investigated. For the uranium-containing mesogens, luminescence can be induced by dissolving them in an ionic: liquid matrix. The europium-containing compound shows intense red photoluminescence with high colour Purity.

Solventless continuous flow homogeneous hydroformylation of 1-octene

The hydroformylation of 1-octene under continuous flow conditions is described. The system involves dissolving the catalyst, made in situ from [ Rh(acac)(CO)(2)] (acacH = 2,4- pentanedione) and [RMIM][TPPMS] ( RMIM = 1-propyl (Pr), 1-pentyl (Pn) or 1-octyl (O)-3-methyl imidazolium, TPPMS = Ph2P(3-C6H4SO3)), in a mixture of nonanal and 1-octene and passing the substrate, 1-octene, together with CO and H-2 through the system dissolved in supercritical CO2 (scCO(2)). [PrMIM][TPPMS] is poorly soluble in the medium so heavy rhodium leaching (as complexes not containing phosphine) occurs in the early part of the reaction. [PnMIM][ PPMS] affords good rates at relatively low catalyst loadings and relatively low overall pressure (125 bar) with rhodium losses <1 ppm, but the catalyst precipitates at higher catalyst loadings, leading to lower reaction rates. [OMIM][ TPPMS] is the most soluble ligand and promotes high reaction rates, although preliminary experiments suggested that rhodium leaching was high at 5-10 ppm. Optimisation aimed at balancing flows so that the level within the reactor remained constant involved a reactor set up based around a reactor fitted with a sight glass and sparging stirrer with the CO2 being fed by a cooled head HPLC pump, 1-octene by a standard HPLC pump and CO/H-2 through a mass flow controller. The pressure was controlled by a back pressure regulator. Using this set up, [OMIM][ TPPMS] as the ligand and a total pressure of 140 bar, it was possible to control the level within the reactor and obtain a turnover frequency of ca. 180 h(-1). Rhodium losses in the optimised system were 100 ppb. Transport studies showed that 1-octene is preferentially transported over the aldehydes at all pressures, although the difference in mol fraction in the mobile phase was less at lower pressures. Nonanal in the mobile phase suppresses the extraction of 1-octene to some extent, so it is better to operate at high conversion and low pressure to optimise the extraction of the products relative to the substrate. CO and H2 in the mobile phase also suppress the extraction effciency by as much as 80%.

Solubilization of an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate, in a surfactant-water system

The amphiphilic association structures were determined in the system; water, Laureth 4 (approximately C-12(EO)(4)), and the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]), using visual observation and small angle x-ray diffraction. The system showed a lamellar liquid crystal solubilizing the ionic liquid ([bmim][PF6]) to a maximum of 15%, an isotropic surfactant solution dissolving the ionic liquid to a maximum of 39%, an isotropic ionic liquid solution with less than 0.5% of water and surfactant and finally, an aqueous solution with only traces of surfactant and ionic liquid. The small angle x-ray diffraction results showed the ionic liquid to be solubilized into the lamellar liquid crystal without changing the dimensions of the amphiphile layer or the interlayer spacing dependence on the water content.

Photostability of a highly luminescent europium beta-diketonate complex in imidazolium ionic liquids

A high quantum yield and an enhanced photostability was found for a europium(III) tetrakis(2-thenoyltrifluoroacetonate) complex after dissolving the complex in a weakly-coordinating imidazolium ionic liquid.

Microneedle Arrays Allow Lower Microbial Penetration Than Hypodermic Needles In Vitro

Methods: In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models.

Results: When employing Silescol® membranes, the numbers of Candida albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the membranes were an order of magnitude lower when the membranes were punctured by microneedles rather than a 21G hypodermic needle. Apart from the movement of C. albicans across hypodermic needle-punctured membranes, where 40.2% of the microbial load on control membranes permeated the barrier over 24 h, the numbers of permeating microorganisms was less than 5% of the original microbial load on control membranes. Experiments employing excised porcine skin and radiolabelled microorganisms showed that the numbers of microorganisms penetrating skin beyond the stratum corneum were approximately an order of magnitude greater than the numbers crossing Silescol® membranes in the corresponding experiments. Approximately 103?cfu of each microorganism adhered to hypodermic needles during insertion. The numbers of microorganisms adhering to MN arrays were an order of magnitude higher in each case.

Conclusion: We have shown here that microneedle puncture resulted in significantly less microbial penetration than did hypodermic needle puncture and that no microorganisms crossed the viable epidermis in microneedle—punctured skin, in contrast to needle-punctured skin. Given the antimicrobial properties of skin, it is, therefore, likely that application of microneedle arrays to skin in an appropriate manner would not cause either local or systemic infection in normal circumstances in immune-competent patients. In supporting widespread clinical use of microneedle-based delivery systems, appropriate animal studies are now needed to conclusively demonstrate this in vivo. Safety in patients will be enhanced by aseptic or sterile manufacture and by fabricating microneedles from self-disabling materials (e.g. dissolving or biodegradable polymers) to prevent inappropriate or accidental reuse.

Rhodium carbenoid O-H insertion reactions with phenols; a facile method for the synthesis of trialkyl 2-aryloxyphosphonoacetates and their use in the preparation of 2-aryloxy-3-phenylpropanoates

Substituted phenols undergo a facile Rh carbenoid-mediated O-H insertion reaction with (EtO)2P(O)C(:N2)CO2R (I; R = Et, Me) to give 44-86% 2-aryloxyphosphonoacetates II (R1 = e.g., H, 4-Me, 4-Cl, 2-OH, 4-PhCH2O). Phenols contg. strongly electron withdrawing groups, bulky ortho-substituents or certain ortho-heteroatom substituents show reduced or variable yields. Catechol affords a mono-adduct which cyclizes to lactate III. Aniline inserts preferentially and exclusively over phenol in a competition reaction with I (R = Et) to give (EtO)2P(O)CH(NHPh)CO2Et. II are versatile intermediates in a prepn. of 2-aryloxy-3-phenylpropenoates IV by Wadsworth-Emmons reaction with benzaldehydes R2C6H4CHO (R2 = PhCH2O, 2-Cl, H). Dissolving Mg metal redn. provides a mild method for the conversion of propenoates IV into the corresponding propanoates.