Development of a stick-type transdermal eyelid delivery system of ketotifen fumarate for ophthalmic diseases

A transdermal eyelid delivery system for treating ocular diseases (eye-stick) has been developed. Ketotifen fumarate (KT) was used as a model drug. An in vivo study using rabbits showed that the eye-stick device maintained a constant conjunctival concentration of the drug for an extended period of time, which was equivalent or higher than the therapeutic level following eye drop administration. Moreover, the conjunctival concentration after eye-stick application was well predicted using the physicochemical parameters, diffusion coefficient and partition coefficient, obtained from in vitro hairless mouse skin permeation experiments.     

Reaction of triarylphosphine radical cations generated from photoinduced electron transfer in the presence of oxygen

[reaction: see text] The 9,10-dicyanoanthracene (DCA)-sensitized photoreaction of triarylphosphines (1) was carried out in acetonitrile under aerobic conditions. Phosphine 1 was oxidized to the corresponding phosphine oxide with no appreciable side reactions. Product analysis and laser flash photolysis experiments suggest that the radical cation of 1 formed by the electron transfer from 1 to DCA in the singlet excited state ((1)DCA) reacts with O(2) to eventually afford the phosphine oxide.     

Acoustic trapping as a generic non-contact incubation site for multiplex bead-based assays

In this study, we show a significantly reduced assay time and a greatly increased bead recovery for a commercial Luminex-based multiplex diagnostic immunoassay by performing all liquid handling steps of the assay protocol in a non-contact acoustic trapping platform.     

Reactivity of triarylphosphine peroxyl radical cations generated through the reaction of triarylphosphine radical cations with oxygen

One-electron oxidation of triarylphosphines (Ar3P, Ar = phenyl and substituted phenyl) in benzonitrile (PhCN) has been studied using pulse radiolysis technique. One-electron oxidation of Ar3P occurred to yield the radical cation (Ar3P*+) which showed an intense absorption with a peak at 360-370 nm together with a broad band at 500-600 nm. The addition of molecular oxygen (O2) to the phosphorus atom of Ar3P*+ took place at the second-order rate constant of 10(7)-10(9) dm(3) mol(-1) s(-1) to yield the peroxyl triarylphosphinyl radical cation (Ar3P+OO*). It is found that the electron-releasing substituents on the para position of the phenyl ring of Ar3P influence the rate constants of the reaction of Ar3P*+ with O2 and that o-methyl substituents on the phenyl ring influence the reactivity of Ar3P+OO*.     

Exclusion of aromatic radical cations from cyclodextrin nanocavity studied by pulse radiolysis

The influence of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the one-electron oxidation reaction of aromatic sulfides (S) with Br2*- and the decay process of the S radical cation (S*+) was investigated by pulse radiolysis. The dissociation kinetics of S*+ from the CD cavity was examined in terms of the apparent equilibrium constants (Kapp) for the formation and decay processes of S*+. Inhibition of the one-electron oxidation reaction of S by Br2*- was clearly observed in the presence of HP-beta-CD. On the basis of a comparison between the determined Kapp values, it was found that the binding ability of S*+ with HP-beta-CD is much lower than that of S, because of the hydrophobic nature of the cavity. The formation process of the dimer radical cation of 4-(methylthio)phenylmethanol ((MTPM)2*+), which is generated between MTPM(*+) and neutral MTPM in solution, was also inhibited by the addition of HP-beta-CD.     

Sulfonated Pyrene as a Photoregulator for Single-Stranded DNA Looping

Controlling the conformation and function of biomolecules through photoregulators holds great promise as a spatiotemporally controllable tool for disease control. In addition, introducing photoregulators into biomolecules has also found applications in constructing smart nanomaterials. In spite of the astonishing advances that have been made in the past few years, realizing highly controllable and efficient regulation over the conformation and function of biomolecules under physiological conditions is still challenging. Herein, sulfonated pyrene SPy was synthesized and used as a photoregulator to control the looping of single-stranded DNAs (ssDNAs) in aqueous solution. Due to its water solubility, SPy merits use in the study of biomolecules in aqueous solution. The looping of the doubly SPy -modified ssDNAs is stimulated by irradiation and regulated by SPy . Photoionization generates the radical cation of SPy ( SPy ^.+). The association of SPy ^{. +} with its neutral counterpart, SPy , gives rise to the dimer radical cation of SPy ( SPy₂ ^{. +} ). During the association process, the stabilization energy released to form SPy₂ ^{. +} provides a driving force for the looping of ssDNAs. Conversely, the formed loop conformations were trapped by the formation of SPy₂ ^{. +} , and this allowed the looping dynamics to be investigated. The results reported herein suggest potential of SPy as a photoregulator for controlling the conformation and function of biomolecules under physiological conditions.     

Evaluation of the predicted time-concentration profile of serum tulobuterol in human after transdermal application

We proposed an in vitro/in vivo/in silico method for evaluating the clinical performance of matrix type transdermal therapeutic systems (TTSs). This method is based on the following four approaches: (1) drug release experiment, (2) in vitro penetration experiment using excised hairless mouse skin, (3) clinical pharmacokinetic study, and (4) mathematical model for evaluating the pharmacokinetic profile. The tulobuterol TTS was used as an example of a matrix type TTS in this study. The drug diffusion coefficient in the matrix device was calculated from the result of the release experiment. The drug diffusion coefficient and the partition coefficient in the skin were calculated from the results of in vitro skin penetration experiments where hairless mice and rats were used. Those parameters were used as substitutes of human. Further, these parameters were used for solving the governing partial differential equation on skin penetration. The time profiles of the serum concentration in human after applying the tulobuterol TTS were predicted and compared with the clinical data. The predicted profiles obtained from the data of hairless mice reproduced the influence of drug depletion adequately and well agreed with the clinical data, while those from the data of rats differed clearly in the initial rise. This method is useful for prediction of pharmacokinetic profiles of TTSs.     

Physical Properties of the Ternary Mixture Ethanol+Water+1-Butyl-3-Methylimidazolium Chloride at 298.15 K

In this work densities, refractive indices, speeds of sound and isentropic compressibilities of the ternary mixture ethanol+water+1-butyl-3-methylimidazolium chloride ([C₄mim][Cl]), and of the binary subsystems containing the ionic liquid, have been measured at 298.15 K and atmospheric pressure.     

Defect structures in nematic liquid crystals around charged particles

We numerically study the orientation deformations in nematic liquid crystals around charged particles. We set up a Ginzburg-Landau theory with inhomogeneous electric field. If the dielectric anisotropy e₁ \varepsilon_{1}^{} is positive, Saturn-ring defects are formed around the particles. For e₁ \varepsilon_{1}^{} < 0 , novel “ansa” defects appear, which are disclination lines with their ends on the particle surface. We find unique defect structures around two charged particles. To lower the free energy, oppositely charged particle pairs tend to be aligned in the parallel direction for e₁ \varepsilon_{1}^{} > 0 and in the perpendicular plane for e₁ \varepsilon_{1}^{} < 0 with respect to the background director. For identically charged pairs the preferred directions for e₁ \varepsilon_{1}^{} > 0 and e₁ \varepsilon_{1}^{} < 0 are exchanged. We also examine competition between the charge-induced anchoring and the short-range anchoring. If the short-range anchoring is sufficiently strong, it can be effective in the vicinity of the surface, while the director orientation is governed by the long-range electrostatic interaction far from the surface.     

Synthesis of a Ni Complex Chelated by a [2.2]Paracyclophane-Functionalized Diimine Ligand and Its Catalytic Activity for Olefin Oligomerization

A diimine ligand having two [2.2]paracyclophanyl substituents at the N atoms (L1) was prepared from the reaction of amino[2.2]paracyclophane with acenaphtenequinone. The ligand reacts with NiBr₂(dme) (dme: 1,2-dimethoxyethane) to form the dibromonickel complex with (R,R) and (S,S) configuration, NiBr₂(L1). The structure of the complex was confirmed by X-ray crystallography. NiBr₂(L1) catalyzes oligomerization of ethylene in the presence of methylaluminoxane (MAO) co-catalyst at 10–50 °C to form a mixture of 1- and 2-butenes after 3 h. The reactions for 6 h and 8 h at 25 °C causes further increase of 2-butene formed via isomerization of 1-butene and formation of hexenes. Reaction of 1-hexene catalyzed by NiBr₂(L1)–MAO produces 2-hexene via isomerization and C12 and C18 hydrocarbons via oligomerization. Consumption of 1-hexene of the reaction obeys first-order kinetics. The kinetic parameters were obtained to be ΔG^‡ = 93.6 kJ mol⁻¹, ΔH^‡ = 63.0 kJ mol⁻¹, and ΔS^‡ = −112 J mol⁻¹deg⁻¹. NiBr₂(L1) catalyzes co-dimerization of ethylene and 1-hexene to form C8 hydrocarbons with higher rate and selectivity than the tetramerization of ethylene.