Hyaluronic acid in ocular drug delivery.

As a naturally-occurring polysaccharide which could be found in various ophthalmic tissues, hyaluronic acid (HA) has a wide range of applications in the eye, including treatment of dry eye, vitreous substitutes and ophthalmic viscosurgical devices. Besides that, HA can be used as an effective drug carrier for ocular disease treatment due to its excellent biocompatibility, biodegradability, bioadhesion properties, viscoelasticity and receptor interaction characteristic. This review summarizes recent advances in HA-based drug delivery systems for ocular disease treatment in which it could be used as drug-polymer conjugate, drug carrier substrates, and surface modifications of the carrier. To achieve the optimum drug delivery efficacy under varied ophthalmic diseases, the molecular weight (MW) and amount of HA should be selected rationally and applied to design diverse delivery systems.

Virus Mimetic Shell-Sheddable Chitosan Micelles for siVEGF Delivery and FRET-Traceable Acid-Triggered Release.

Targeting vascular endothelial growth factor (VEGF) using small interfering RNA (siVEGF) has shown great potential in inhibiting the growth, proliferation, and migration of tumors by reducing the proliferation of blood vessels. On the basis of bionic principles, a novel pH-responsive and virus mimetic shell-sheddable chitosan (CS) micelles (CMs) as siRNA delivery system was introduced in this study. The cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) modified poly(enthylene glycol) (PEG) was conjugated to the HA2 modified chitosan via a hydrazone linkage (cRGD-PEG-Hz-CS-HA2). The cRGD-PEG-Hz-CS-HA2 conjugate could form micelles by interacting with the complex of octanal, Boc-l-lysine, and 9-d-arginine (9R) (octyl-Lys-9R) as a hydrophodic core forming agent, termed as cRGD-PEG-Hz-CS-HA2/octyl-Lys-9R (abbreviated as cRGD/HA2/Hz-CMs).The CMs modified with cRGD can accurately target glioma cells (U87MG cells) with high expression of αvß3. The payloads of siVEGF were packed into the core of cRGD/HA2/Hz-CMs via electrostatic interaction and hydrophobic interaction. The intracellular cargo release was achieved by the pH-responsive lysis of the hydrazone bond in acidic environment of endosome. Moreover, the exposed HA2, as a pH-sensitive membrane-disruptive peptide, assists the escape of the carriers from endosome into cytosol. In addition, cRGD/HA2/Hz-CMs can effectively deliver siVEGF and silence VEGF gene expression in U87MG cells, leading to the significant tumor growth inhibition. This study demonstrates that cRGD/HA2/Hz-CMs can deliver and release siVEGF in a controlled manner, which was traced by the fluorescence resonance energy transfer (FRET) system in order to achieve RNAi-based anti-angiogenic treatment of cancer in vivo.

Modified mussel shell powder for microalgae immobilization to remove N and P from eutrophic wastewater.

In this work, calcined mussel shell powder (CMSP) was activated by K2CO3 (K-CMSP), and this porous K-CMSP surface was modified by L-arginine (L-ARG) to render porous biomass a positively charged surface, which was innovatively utilized as a carrier to immobilize microalgae by adsorption via electrostatic interactions. The pore and the surface structures of CMSP and K-CMSP were characterized by XRD, FTIR, BET and SEM. The surface morphology of immobilized microalgae was visualized via using inverted optical microscope and SEM. It was found that microalgae could survive for 60 days, and the loss rate of chlorophyll-a preserved at -24 °C was the lowest, 44.73%. The microalgae could revive to normal growth level within 10 days and the cell content of microalgae was the highest at 25 °C, 2.8022 × 106 cell/mL. At 25 °C, the highest removal rate of N and P was obtained about 95.0% and 88.63%, respectively.

Calcined Mussel Shell Powder (CMSP) via Modification with Surfactants: Application for Antistatic Oil-Removal.

Biomass is known to efficiently adsorb pollutants from wastewater. In this paper, we demonstrated that a new antistatic oil-cleaning material can be prepared and assembled by using two surfactants, alkyl polyglucosides (APG) and dimethyl octadecyl hydroxy ethyl ammonium nitrate (SN), to modify calcined mussel shell powder (CMSP) through a two-step hydrotherm-assisted adsorption. The pore size and structure of CMSP was measured by BET and a contact angle meter was used to characterize the surface wetting ability. XRD, FTIR, XPS, SEM, TEM, and HRTEM were employed to determine the surface structure of CMSP modified by surfactants APG and SN (MMO). In order to further characterize properties of the surface morphology and crystal structure, the HRTEM was employed to show that the MMO surface had a single crystal structure: calcite, with a crystal plane spacing of 0.2467 nm. The surface of MMO appeared to be fluffy and disperse. The antistatic and degreasing ability of as-prepared samples (MMO) was evaluated by a ZC-36 high resistance meter and BD-457 whiteness meter. The results showed that when the calcination temperature of CMSP reached 1000 °C, and the addition amount of APG and SN was 0.8 g and 0.16 g, it had an optimum antistatic effect with a surface resistivity (Rs) of 1.35 × 108 Ω, and a detergency rate to oil of 17.35%. This study aims to embrace a green solution to reduce environmental pressure and make use of waste, which is of great significance to environmental protection.

A test strip platform based on DNA-functionalized gold nanoparticles for on-site detection of mercury (II) ions.

A test strip, based on DNA-functionalized gold nanoparticles for Hg(2+) detection, has been developed, optimized and validated. The developed colorimetric mercury sensor system exhibited a highly sensitive and selective response to mercury. The measurement principle is based on thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination chemistry and streptavidin-biotin interaction. A biotin-labeled and thiolated DNA was immobilized on the gold nanoparticles (AuNPs) surface through a self-assembling method. Another thymine-rich DNA, which was introduced to form DNA duplexes on the AuNPs surface with thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination in the presence of Hg(2+), was immobilized on the nitrocellulose membrane as the test zone. When Hg(2+) ions were introduced into this system, they induced the two strands of DNA to intertwist by forming T-Hg(2+)-T bonds resulting in a red line at the test zone. The biotin-labeled and thiolated DNA-functionalized AuNPs could be captured by streptavidin which was immobilized on the nitrocellulose membrane as the control zone. Under optimized conditions, the detection limit for Hg(2+) was 3 nM, which is lower than the 10nM, maximum contaminant limit defined by the US Environmental Protection Agency (EPA) for drinking water. A parallel analysis of Hg(2+) in pool water samples using cold vapor atomic absorption spectrometry showed comparable results to those obtained from the strip test. Therefore, the results obtained in this study could be used as basic research for the development of Hg(2+) detection, and the method developed could be a potential on-site screening tool for the rapid detection of Hg(2+) in different water samples without special instrumentation. All experimental variables that influence the test strip response were optimized and reported.

Electrochemiluminescence immunosensor based on graphene-CdS quantum dots-agarose composite for the ultrasensitive detection of alpha fetoprotein.

A novel strategy for the enhancement of electrochemiluminescence (ECL) was developed by combining CdS quantum dots (QDs), graphene (G) and agarose. This enhanced ECL was exploited to develop a label-free ECL immunosensor for the ultrasensitive detection of alpha fetoprotein (AFP). The novel G-CdS QDs-agarose composite was first coated on the glass carbon electrode surface to form a robust film, which exhibited high ECL intensity, good biocompatibility and high stability. After that 3-aminopropyl-triethoxysilane (APS), as a binding linker, was conjugated to the G-CdS QDs-agarose composite film on the electrode, the ECL signal was significantly enhanced. The fabrication of ECL immunosensor was successfully completed by immobilizing the AFP-antibody (Ab) onto the electrode through glutaric dialdehyde (GLD). The specific immunoreaction between AFP and antibody resulted in the decrease in ECL intensity and the intensity decreased linearly with the logarithm of AFP concentration in the range of 0.0005-50 pg mL(-1) with a detection limit of 0.2 fg mL(-1). The immunosensor exhibits high sensitivity, specificity, stability, reproducibility and good regeneration, thus has the potential to be used in clinical application. Besides, the highly enhanced ECL from the G-CdS QDs-agarose composite film opened new avenues to apply graphene and QDs ECL in analytical systems and ECL biosensors.

Aqua-trinitrato[2,4,6-tris-(pyridin-2-yl)-1,3,5-triazine]neodymium(III) dihydrate.

In the title compound, [Nd(NO(3))(3)(C(18)H(12)N(6))(H(2)O)]·2H(2)O, the Nd(3+) ion is in a distorted bicapped square-anti-prismatic geometry formed by three N atoms from the 2,4,6-tris-(pyridin-2-yl)-1,3,5-triazine (TPTZ) ligand, six O atoms from the three nitrate anions and one O atom from the aqua ligand. The mol-ecules are linked by O-H⋯O and O-H⋯N hydrogen bonds. Two types of π-π stacking inter-actions occur between the TPTZ ligands of adjacent complexes [centroid-to-centroid distances = 3.760 (4) and 3.870 (3) Å].

Determination of melamine in dairy products by an electrochemiluminescent method combined with solid-phase extraction.

An electrochemiluminescence (ECL) enhancement method combined with solid-phase extraction has been developed for the determination of melamine in dairy products. It was found that melamine in a strong base solution is able to enhance the ECL of Ru(bpy)(3)(2+) at glass carbon electrode. The optimum experimental conditions for the determination of trace melamine by ECL, such as scan mode and scan rate of the applied potential, the type of buffer solutions and their pH conditions, were investigated. Under optimized conditions, the enhanced ECL intensity was linearly proportional to the logarithm of melamine concentration in the range of 0.01-1.0 ppb, and the detection limit was 0.003 ppb. The method has been successfully demonstrated to determine melamine in dairy products including liquid milk, yogurt and milk powder samples. The relative standard deviations ranging from 5.3% to 11.2% and the recoveries from 95.2% to 102.4% were acquired by this method. A possible mechanism for the ECL enhancement effect was also proposed.

Determination of six phthalic acid esters in orange juice packaged by PVC bottle using SPE and HPLC-UV: application to the migration study.

A high-performance liquid chromatographic assay is described for the determination of six phthalic acid esters (PAEs) in orange juice packaged in polyvinyl chloride (PVC) bottle. Samples were extracted by solid-phase extraction (SPE) cartridges and separated by a C18 column. The calibration curves were all linear with a correlation coefficient r > 0.9900. The limits of detection for the assay ranged from 2.6 to 13.8 ng/mL. Expressed as the within- and between-day coefficient of variation (CV), precision was 1.4-13.4% and 1.9-13.3%, respectively, and relative errors were 7.6-12.8% and -9.0-14.2%, respectively. The recovery ranged from 76.8 to 112.3% with the CV from 0.3 to 11.3%. The proposed methodology was applied for studing the migration of the selected PAEs into orange juice packaged in PVC bottle. Di-ethyl phthalate (DEP) and di-(2-ethylhexyl) phthalate (DEHP) were detected in the orange juice without the other four PAEs. Concentrations would increase with the storage time and reach up to 0.385 µg/mL and 0.662 µg/mL, respectively, when the expiration date arrived. The level of DEHP was about 110 times higher than the limiting one in drink water (6 ppb) regulated by U.S. EPA. Results suggest that PVC plasticized by DEHP should not be used as the packaging material for orange juice.

Development and application of a method for analysis of phthalates in ham sausages by solid-phase extraction and gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry assay was developed and successfully applied for the determination of phthalates in ham sausage migrated from packaging film. The phthalates studied were dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzylbutyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), with dibutyl adipate (DBA) as internal standard. The sample pre-treatments included extraction with n-hexane, solvent evaporation and reconstitution with acetonitrile before and after solid-phase extraction (SPE). The extraction and cleaning up procedure was carried out with cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 87.3%. The calibration curves obtained were linear with correlation coefficients greater than 0.99. The method proved to be accurate and precise for the six phthalates used. It was successfully applied to a study on the migration of phthalates from packaging PVC film into ham sausage.

Simultaneous determination of phthalates and adipates in human serum using gas chromatography-mass spectrometry with solid-phase extraction.

A gas chromatography-mass spectrometry assay was developed and validated for the simultaneous determination of phthalates and adipates in human serum. The phthalates and adipates studied were dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate, di-n-octyl phthalate, diethyl adipate, dibutyl adipate, diisobutyl adipate, bis(2-butoxyethyl) adipate and di-2-ethylhexyl adipate, with diisooctyl phthalate as internal standard. The extraction and cleaning up procedure was carried out with solid-phase extraction cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 88% for each analyte and the internal standard. The calibration curves obtained were linear with correlation coefficients greater than 0.98. For all analytes, the assay gave CV% values for intra-day precision from 4.9 to 13.3% and mean accuracy values from 91.4 to 108.4%, while inter-day precision was 5.2-13.4% and mean accuracy 91.0-110.2%. The limits of detection for the assay of phthalates and adipates were in the range 0.7-4.5 ng/mL. The method is simple, sensitive and accurate, and allows for simultaneous determination of nanogram levels of phthalates and adipates in human serum. It was successfully applied to an investigation on the level of phthalates and adipates in a non-occupationally exposed population.

Determination of trace mercury species by high performance liquid chromatography-inductively coupled plasma mass spectrometry after cloud point extraction.

A sensitive method for speciation analysis of inorganic mercury (Hg(2+)) and methyl mercury (MeHg(+)) has been developed by using high performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectrometry (ICP-MS) after cloud point extraction. The analytes were complexed with sodium diethyldithiocarbamate (DDTC) and preconcentrated by a non-ionic surfactant Triton X-114. Mercury species were effectively separated by HPLC in less than 6 min. The enhancement factors for 25 mL sample solution were 42 and 21, and the limits of detection were 4 and 10 ng L(-1) for Hg(2+) and MeHg(+), respectively. The developed method was successfully applied to the determination of trace amount of mercury species in environmental and biological samples.

Poly[[tetra-aqua-bis[µ(4)-2,2'-(p-phenyl-ene-di-oxy)diacetato][µ(2)-2,2'-(p-phenyl-ene-di-oxy)diacetato]dierbium(III)] hexa-hydrate].

The asymmetric unit of the title compound, [Er(2)(C(10)H(8)O(6))(3)(H(2)O)(4)]·6H(2)O, comprises one Er(3+) ion, one and a half 2,2'-(p-phenyl-enedi-oxy)diacetate (hqda) ligands, two coordinated water mol-ecules and three uncoordinated water mol-ecules. The Er(3+) ion is nine-coordinated by seven O atoms from hqda ligands and two O atoms from water mol-ecules. In the title compound, there are two types of crystallographically independent ligands: one with an inversion center in the middle of the ligand is chelating on both ends of the ligand towards each one Er center; the other hqda ligands are bridging-chelating on one side, and bridging on the other end of the ligand. Two adjacent Er(3+) ions are thus chelated and bridged by -COO groups from hqda ligands in three coordination modes (briding-chelating, bridging and chelating). These building blocks are linked by OOC-CH(2)O-C(6)H(4)-OCH(2)-COO spacers, forming two-dimensional neutral layers. Adjacent layers are linked by O-H⋯O hydrogen-bonding inter-actions, forming a three-dimensional supermolecular network.

catena-Poly[diaqua-tris(µ(3)-biphenyl-2,2-dicarboxyl-ato)disamarium(III)].

The title compound, [Sm(2)(C(14)H(8)O(4))(3)(H(2)O)(2)](n), is composed of one-dimensional chains and is isostructural with previously reported compounds [Wang et al. (2003 ▶). Eur. J. Inorg. Chem. pp. 1355-1360]. The asymmetric unit contains two Sm atoms, each of which lies on a crystallographic twofold axis. Both crystallographically independent Sm atoms are coordinated by eight O atoms in a distorted dodeca-hedral arrangement. The polymeric chains run along [001]. Adjacent chains are connected through π-π inter-actions [centroid-centroid distance = 3.450 (2) Å], forming a two-dimensional supra-molecular network.

Simultaneous determination of rivanol and mifepristone in human plasma by a HPLC-UV method with solid-phase extraction.

A HPLC method with UV detection was developed and validated for the simultaneous determination of rivanol and mifepristone in human plasma. Norethisterone was used as the internal standard. Separation was performed by a C18 reversed-phase column maintained at 20 degrees C. The mobile phase was a mixture of methanol-acetonitrile-0.05% sodium dodecylsulfonate in a 0.05 M phosphate buffer with the pH adjusted to 3.0 (30:30:40, v/v/v) at a flow rate of 0.8 ml/min. Dual wavelength mode was used, with mifepristone monitored at UV 302 nm, while rivanol and norethisterone at 272 nm. A reliable biological sample pre-treatment procedure by means of solid-phase extraction was used, which allowed to obtain good extraction efficiency (>93%) for both of the analytes and the internal standard. The calibration curves were both linear with the correlation coefficient r equal to 0.9999. For rivanol, the assay gave CV% values for precision always lower than 7.8% and mean accuracy values higher than 95.3%. As to mifepristone, precision was always lower than 10.1% and mean accuracy values were higher than 93.8%. The limit of detection for the assay of rivanol and mifepristone was 1.1 and 3 ng/ml, respectively. The method is simple, sensitive and accurate, and allow for simultaneous determination of nanogram levels of rivanol and mifepristone in human plasma. It could be applied to assess the plasma level of rivanol and mifepristone in women undergoing polypharmacy with the two drugs.

Development of a high-performance liquid chromatographic method for the determination of mifepristone in human plasma using norethisterone as an internal standard: application to pharmacokinetic study.

OBJECTIVE: The objective of this study was to develop a simple, sensitive, stable and validated HPLC method for the determination of mifepristone levels in human plasma. METHODS: Solid-phase extraction cartridges were used to extract plasma samples. Separation was carried out on a C(18) column maintained at 20 degrees C with acetonitrile-water (80:20, v/v) as mobile phase at a flow rate of 0.6 mL/min. Norethisterone was employed as the internal standard. Dual wavelength mode was used, with mifepristone monitored at UV 302 nm and norethisterone at 240 nm. RESULTS: The calibration curve was linear in the concentration range of 5-10000 ng/mL, with linear correlation coefficient r being 0.9999. The limit of detection for the assay was 3 ng/mL. The inter-day accuracy ranged from 92.4% to 98.4% and precision 3.6% to 11.4%. The intra-day accuracy ranged from 92.1% to 100.6% and precision 4.7% to 12.2%. The absolute recovery was 91.7-100.1%. Plasma samples were stable for at least 1 month if stored at -20 degrees C. This validated HPLC method was successfully applied to pharmacokinetic study of mifepristone in human plasma samples collected from volunteers after oral administration of 10 mg mifepristone. CONCLUSION: The simple, accurate and stable method allows the sensitive determination of mifepristone in human plasma at the nanogram level. It could be applied to assess the plasma level of mifepristone in women up to 5 days after oral administration of 10 mg mifepristone.

Determination of ng rivanol in human plasma by SPE-HPLC method.

A high-performance liquid chromatography assay is described for the determination of rivanol in human plasma. Solid-phase extraction cartridges are used to extract plasma samples. Separation is done by using a C18 column. The mobile phase is a mixture of methanol-0.05% sodium dodecylsulfonate (70:30, v/v, pH 3), with the flow rate at 1.0 mL/min. UV detection of rivanol is at 272 nm. The calibration curve is linear in the concentration range of 1x10(-8) mol/L to 1x10(-5) mol/L with linear correlation coefficient r equal to 0.9998. The limit of detection for the assay is 3x10(-9) mol/L, corresponding to 1.1 ng/mL. Precision, expressed as the within- and between-day coefficient of variation, is 3.3-8.1% and 4.1-9.5%, respectively, at plasma control samples of 5x10(-8), 5x10(-7), and 5x10(-6) mol/L. And the recovery ranges from 94.8% to 107.2%. The selectivity of the method is confirmed. Plasma samples are stable for at least 15 days if they are stored lightproof at -20 degrees C. This method is simple, sensitive, and accurate, and it allows for the determination ng rivanol in human plasma. It could be applied to assessing its plasma level in women receiving an intra-amniotic injection of rivanol.

An HPLC method for the determination of ethacridine lactate in human urine.

An HPLC method was developed and validated for the determination of ethacridine lactate in human urine. Solid-phase extraction cartridges were used to extract urine samples. Separation was carried out on a C(18) column maintained at 30 degrees C with methanol-0.05% sodium dodecylsulfonate (70:30, v/v, pH 3) as mobile phase at a flow rate of 1.0 mL/min. Detection was at UV 272 nm. The calibration curve was linear in the concentration range of 4-4000 ng/mL, with linear correlation coefficient r equal to 0.9998. The limit of detection for the assay was 1.1 ng/mL. The within-day accuracy ranged from 94.8 to 101.6% and precision from 2.3 to 5.4%. The between-day accuracy ranged from 96.8 to 102.6% and precision from 4.0 to 5.3%. The absolute recovery was 95.4-101.2%. Urine samples were stable for at least 15 days if stored in the dark at -20 degrees C. This simple and accurate method allows the sensitive determination of ethacridine lactate in human urine. It was successfully applied to assess the urine level of ethacridine lactate in women received intra-amniotic injection.

Bis(2,2'-biimidazole-κN,N')bis-(2-bromo-fumarato-κO)copper(II).

In the title compound, [Cu(C(4)H(2)BrO(4))(2)(C(6)H(6)N(4))(2)], the central Cu(II) atom lies on an inversion center and is six-coordinated in an octahedral geometry by four N atoms from two chelating biimidazole mol-ecules in the equatorial plane and two O atoms from two 2-bromo-fumarate ligands in the axial positions. O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds lead to a three-dimensional network.