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Malignant gliomas manifest frequent tumor recurrence after surgical resection and/or other treatment because of their nature of invasiveness and dissemination. The recognized brain tumor-tracking property of neural progenitor/stem cells opened the possibility of targeting malignant brain tumors using neural progenitor/stem cells. We and others have previously shown that fetal neural progenitor/stem cells can be used to deliver therapeutic molecules to brain tumors. Our recent work has further shown that gene delivery by bone marrow–derived neural progenitor/stem cells achieves therapeutic effects in a glioma model. In this study, we isolate and characterize bone marrow–derived neural progenitor/stem cells, which also express the chemokine receptor chemokine CXC receptor 4 (CXCR4). We show that CXCR4 is required for their chemotaxis and extracellular matrix invasion against a gradient of glioma soluble factors. Furthermore, β-galactosidase-labeled bone marrow–derived neural progenitor/stem cells implanted in the contralateral side of the brain were shown to track gliomas as early as day 1 and increased through days 3 and 7. Intracranial glioma tracking by bone marrow–derived neural progenitor/stem cells is significantly inhibited by preincubation of bone marrow–derived neural progenitor/stem cells with a blocking anti–CXCR4 antibody, suggesting a CXCR4–dependent tracking mechanism. Glioma tracking bone marrow–derived neural progenitor/stem cells were found to express progenitor/stem cell markers, as well as CXCR4. Although bromodeoxyuridine incorporation assays and proliferating antigen staining indicated that tumor tracking bone marrow–derived neural progenitor/stem cells were mostly nonproliferating, these cells survive in the local tumor environment with little apoptosis. Elucidating the molecular mechanism of brain tumor tracking by adult source stem cells may provide basis for the development of future targeted therapy for malignant brain tumors. [Mol Cancer Ther 2009;8(9):2746–53]

The cloud-points (CPs) of poly(vinyl stearate) (PVS) in several fluids, such as carbon dioxide (CO2), propane, butane, propylene, 1-butene, and dimethyl ether (DME), and in their mixtures are reported herein. A high-pressure apparatus with a variable-volume view cell was used to measure the CPs of the PVS mixtures. The measured CP pressures for all the systems exhibited a lower critical solution temperature (LCST) phase behavior. The CPs for ternary systems consisting of CO2, DME, propylene, 1-butene, and PVS were distributed over the temperature range of 333−453 K and the pressure range of 35−203 MPa. To understand the effect of interactions between the solvents, co-solvents, and PVS at a molecular level, the perturbed-chain statistical associating fluids theory (PC-SAFT) model was applied to the modeling of these systems, and the predicted results were observed to be consistent with the tendency of experimental data. A theoretical investigation using the PC-SAFT model revealed some important information. The strong interactions between PVS and CO2 resulted in the high solubility of PVS in the CO2/DME mixture, while the weak interactions between CO2 and the co-solvent (i.e., propylene, 1-butene) increased the solubility of PVS in their mixtures.

The phase behavior of poly(ethylene glycol) (PEG) in supercritical solvents such as CO2, propylene, and butene, and in aqueous solution at high pressure are described using the perturbed chain statistical associating fluid (PC-SAFT) model. The effects of the molecular weight of PEG, solvent, pressure, and temperature are investigated. To model the phase behavior of PEG in supercritical solvents, the molecular weight- and temperature-dependence of the binary interaction parameter kij is considered. In addition, modeling of a PEG/CO2/ethanol mixture was carried out. The CO2 molecule was considered as a Lewis acid, and can undergo hydrogen bonding with PEG (forming a PEG-CO2 complex) and ethanol. These cross-associations, as well as the self-association of ethanol, are described in the PC-SAFT model. The correlated pressure and temperature (P-T) isopleth curves show a somewhat difference for binary system at low temperature area (

Poly(ɛ-caprolactone) (PCL) is a biocompatible and biodegradable polymer and is widely used in controlled drug-delivery applications. For the production of polymeric microspheres loaded with pharmaceutical products, the supercritical fluid technology using carbon dioxide (CO2) is favored because of its non-toxic nature. In this work, the phase behavior of PCL in various supercritical solvents such as CO2, CHClF2, dimethyl ether (DME), 1-butene, and propylene is described by the PC-SAFT model. The effects of the molecular weight of PCL, the type of solvent, pressure, temperature, and the concentration of the cosolvent are investigated. The solubility of PCL in supercritical solvents is accurately described over a wide range of temperatures (from 293.15 to 503 K) and for pressures up to 300 MPa. CO2 shows the poorest solubility, while CHClF2 shows the highest solubility. The predicted cloud-point pressures show an increasing tendency with an increase of the molecular weight of the PCL. The addition of cosolvents, i.e., DME and CHClF2, to the PCL/CO2 solution increases of the dissolving power of the mixed solvent. The results predicted with the PC-SAFT equation of state are in good agreement with the experimental data.

The pKa of an acid is important for determining the dissociation and thermodynamic properties of solutions containing it. However, the value of pKa is typically determined at dilute limit and cannot be used to describe properties of the solution at high concentrations. In this work, we propose an approach to determine the concentration independent equilibrium constant Keq based on pKa and predicted activity coefficients. The Keq determined is applied to predict the degree of dissociation over whole concentration range for weak to strong acids. The pH of acid aqueous solution is predicted over whole concentration range, showing a good agreement with experiments. Based on this approach, we found that the vapor pressures of acid aqueous solutions strongly depend on the degree of dissociation of acids. The proposed model provides useful insights to link the macroscopic properties of acid aqueous solutions to its microscopic dissociation phenomena over the whole concentration range.

The specific interaction (i.e., Lewis acid-base interaction) between CO2 and the ether group in poly(ethylene glycol) (PEG) is expected to significantly affect the mutual solubility in CO2/PEG systems. Therefore, in order to understand the liquid-liquid equilibrium (LLE) phase behavior under supercritical CO2, the specific intermolecular interaction between CO2 and PEG should be involved in the theoretical modeling of LLE phase behavior for the PEG/CO2 system. In this work, this interaction (i.e., CO2-PEG complex due to the Lewis acid-base interaction) is treated by the perturbed-chain SAFT (PC-SAFT) model as a cross-association between CO2 and PEG. The cross-association energy parameter is estimated from the experimental enthalpy by the Fourier transform IR (FT-IR) spectroscopy method for CO2 and the ether group in PEG. The correlated pressure and temperature (P-T) isopleth curve with the cross-association between CO2 and PEG is much closer to the experimental data. The degree of cross-association decreases as the temperature increases. This strong cross-association leads to a lower critical solution temperature (LCST) phase behavior, even at supercritical conditions.

Glioblastoma multiforme (GBM), a grade IV astrocytoma as defined by the World Health Organization (WHO) criteria, is the most common primary central nervous system tumor in adults. After treatment with the current standard of care consisting of surgical resection, concurrent temozolomide (TMZ), and radiation, the median survival is only 15 months. The limited and less-effective treatment options for these highly aggressive GBMs call for the development of new techniques and the improvement of existing technologies. Nanotechnology has shown promise in treating this disease, and some nanomaterials have demonstrated the ability to cross the blood–brain barrier (BBB) and remain in GBM tissues. Although the retention of nanoparticles (NPs) in GBM tissue is necessary to elicit an antitumor response, the delivery of the NP needs to be enhanced. Current research in nanotechnology is directed at increasing the active targeting of GBM tissue not only for the aid of chemotherapeutic drug delivery but also for imaging studies. This review is aimed at describing advancements in increasing nanotechnology specificity to GBM tissue.

Poly (lactic acid) (PLA) is typical biocompatible polymer, and is widely used in drug delivery application. For the production of polymeric microspheres loaded with the pharmaceutical, the supercritical fluid technology using carbon difoxide (CO2) is favor because of non-toxic nature. In this work, the phase behaviors of PLA in various supercritical solvents such as dimethyl ether (DME), CO2, chlorodifluoromethane (HCFC-22), difluoromethane, trifluoromethane (HFC-23), 1,1,1,2-tetrafluoroethane, 1,1-difluoroethane are described by PC-SAFT model. One binary interaction parameter without considering temperature-dependency is used over a wide range of temperature and pressure. CO2 shows the poorest solubility, while HCFC-22 and DME show the highest solubility. The predicted cloud-point pressure shows the increasing tendency with an increase of PLA's molecular weight. In addition, the pressure-temperature isopleths for the dl-PLA/CO2 solutions with DME, HCFC-22, and HFC-23 as a cosolvent are investigated. The predicted results for three ternary systems with PC-SAFT model show a good agreement with experimental data.

Poly(ethylene oxide) (PEO) is a biocompatible polymer and is widely used in biomedical application such as drug delivery devices. Such biomedical application is suitable due to high water solubility. However, the mixture of PEO and water is highly anomalous because of strong electrostatic attraction like hydrogen bonding interaction. The hydrogen bonding in PEO/water is an important fact to understand the miscibility (i.e., phase behavior) of PEO in aqueous solution and is influenced by temperature, concentration and pressure. The pressure in these factors has a strong effect on the production of the drug delivery material using supercritical fluid technology. In this work, the degree of hydrogen bonding for each molecule in aqueous PEO solution according to temperature, pressure and concentration has been investigated by perturbed-hard-sphere-chain-association (PHSC-AS) models. According to the increase of water concentration, the degree of hydrogen bonding for water-water self-association is gradually decreased, and that for cross-association between PEO and water are sharply increased. As well, according to the increase of temperature, all types of hydrogen bonding are decreased. The pressure-dependence of hydrogen bonding for each association site was not found up to 320 MPa. Such hydrogen bonding effect is considered in the modeling of phase behavior for aqueous PEO system with closed-loop type with the lower critical solution temperature (LCST) at low temperatures and the upper critical solution temperature (UCST) at high temperatures and hour-glass type up to 430 MPa. In general, the hour-glass type phase behavior is not found at atmospheric pressure and is found at the high-pressure range. The calculated results for liquid-liquid equilibrium (LLE) with closed-loop and hour-glass phase behavior showed a good agreement with experimental data.

In this work, the phase behavior for a binary and ternary mixture of polymer with a tetrahydrofurfuryl acrylate (THFA) repeating unit in supercritical conditions were investigated experimentally and theoretically. High-pressure solubility data for the THFA in supercritical carbon dioxide (CO2) fluid were presented over a broad temperature range from 313.2 K to 393.2 K and up to a pressure of 21.86 MPa. The cloud-point measurements in binary and ternary mixtures for poly(tetrahydrofurfuryl acrylate) [PTHFA] + THFA or dimethyl ether (DME) in supercritical CO2 were carried out up to 456.2 K and 255.34 MPa. When THFA and DME were added as cosolvents the cloud-point for PTHFA + CO2 fluid shifted a lower pressure. The PC-SAFT model was applied to describe the phase behavior for all experimental results, which were adequately modeled. Through theoretical investigation with the PC-SAFT model, it was found that the strong interaction between polymer and CO2 causes wide one fluid for the PTHFA/CO2/THFA system, and the interactions between CO2 and DME molecules have strong effects on the phase behavior for the PTHFA/CO2/DME system.

High pressures phase behavior data for the CO2/tetrahydrofurfuryl methacrylate (THFMA) systems are presented at (313.2–393.2) K and up to 22.07 MPa. The system exhibits the Type-I phase behavior with a continuous mixture-critical curve. The solubilities of poly(tetrahydrofurfuryl methacrylate) [P(THFMA)] + THFMA or dimethyl ether (DME) in supercritical carbon dioxide (CO2) were measured up to 490.5 K and 289.83 MPa. The cloud-point pressure for the P(THFMA) + CO2 system shifts to lower pressures as adding THFMA and DME as a cosolvent. P(THFMA) in pure CO2 did not dissolve up to the temperature of 498 K and pressure of 300.0 MPa. All experimental results with vapor-liquid equilibrium (VLE) for the CO2/THFMA binary system and the cloud-point phase behaviors for the P(THFMA)/CO2/cosolvent ternary systems were adequately modeled by the PC-SAFT equation of state. Calculation of the results with the PC-SAFT model showed that the UCST-type phase behavior is mainly due to governed by the interaction between the same species (i.e., between THFMA and THFMA, and between CO2 and CO2), rather than that between different species (i.e., between THFMA and CO2).

The solubilities of 2-(trimethylsilyloxy)ethyl methacrylate and 3-(trimethoxysilyl)propyl methacrylate in supercritical CO2 fluid were measured at many different temperature (i.e., 313.2, 333.2, 353.2, 373.2 and 393.2 K) and up to 22.49 MPa pressures using variable-volume high pressure view cell by static-type. Both systems have shown the type-I phase behavior. Their solubility curve in supercritical CO2 fluid was obtained by varying the pressure at a fixed temperature. The PC-SAFT equation of state (EoS) was used to correlate experimental data and to predict the critical pressure locus. The calculated results show a good agreement with experimental data.

In this work, the experimental cloud-points in the binary and ternary mixtures for poly(2-phenylethyl methacrylate) [P(2-PEMA)] solutions containing supercritical solvents (i.e., carbon dioxide, propylene, 1-butene, dimethyl ether (DME)) are carried out up to 473 K and 224 MPa. According to the amount of cosolvent (i.e., DME), the cloud-point curves for ternary mixtures of P(2-PEMA) in supercritical solvents (i.e., carbon dioxide, propylene, 1-butene) show the changes from upper critical solution temperature (UCST) behavior to lower critical solution temperature (LCST) behavior. The PC-SAFT equation of state is applied to correlate the phase behaviors of all experimental systems, and the calculated results are shown as a reasonable agreement with experimental data. According to the amount of DME (i.e., cosolvent), the UCST- and LCST-type phase behaviors are described exactly by PC-SAFT EoS with one adjustable binary interaction parameter on which the effect of temperature and/or cosolvent amount is not considered.

Due to the electropositivity of the carbon atom in CO2 which results from its lower electron density compared to that of the oxygen atom, CO2 molecules can act either as proton acceptor or electron acceptor. The specific intermolecular interaction (i.e., Lewis acid-base interaction) between CO2 and organic chemicals with electron donor groups exists, and this phenomenon is supported by many experimental studies using spectrometry and ab initio studies. CO2/alcohol solvent systems under high-pressure conditions are important for supercritical extraction, dehydration of alcohols, and extraction of natural products. Furthermore, the study of the complex between CO2 and alcohols due to the Lewis acid-base interaction is crucial for understanding the solvation process under high-pressure conditions, and for the development of thermodynamic models. In this study, the Lewis acid-base interaction between alcohols and CO2 is treated as a hydrogen bonding interaction, and according to the different association schemes for CO2, the effect on the phase behavior of the CO2/alcohol systems at high pressure was investigated using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) model. Taking into consideration the self-association of CO2 yields a more satisfactory performance in the high-pressure region than it would without, and increasing association sites of CO2 do not lead to a better performance. In addition, the cross-association energy (i.e., Lewis acid-base interaction energy) parameter is estimated by directly regressing the experimental data over the entire temperature and pressure range, and the calculated results show an improved performance even at much higher pressures. It was found that strong cross-association interactions lead to higher cross-association in both liquid and vapor phases, which contributes to the improved phase behavior at high-pressures.

The liquid-liquid equilibrium (LLE) calculation for polymer solutions is essential for processes design of polymerization. The hydrogen bonding in polymer solutions leads to deviate remarkably from normal solutions behaviors. The perturbed hard-sphere-chain-association (PHSC-AS) equation of state (EoS) is applied to calculate the liquid-liquid equilibrium (LLE) of polymer mixtures with hydrogen bonding association such as self- and cross-association with various phase behaviors such as UCST, LCST and closed-loop of polymer solutions. In addition, the calculation results are compared with those obtained by the PC-SAFT EoS, which is known to be useful for calculating phase equilibria of polymer systems. PHSC-AS EoS shows a satisfactory performance for LLE calculation with similar accuracy compared to that with PC-SAFT EoS.

We address the possible occurrence of a minimum extent of dissociation (α) of ionic liquid (IL) in IL-solvent mixtures. This phenomenon, known as the redissociation of IL, is responsible for many interesting composition-dependent properties in such mixtures. A thermodynamic model is developed to provide a semiquantitative prediction on the change of α with solvent concentration. It is found that the occurrence of minimum α coincides with the occurrence of a maximum in the mean activity coefficient of dissociated ions, indicating better solvation of free, dissociated ions both with decreasing and increasing solvent concentration. The favorable solvation of free ions is found to change from long-range ion-solvent dielectric polarization to ion-ion-pair dielectric polarization with decreasing solvent concentration. Therefore, the composition dependence of the IL solution dielectric constants, determined from that of the ion-pair and the solvent, is found to be the most important factor for the presence of redissociation in IL solutions.

Experimental data up to 463.1 K and 269.14 MPa are revealed for binary and ternary mixtures of poly(phenyl methacrylate) [P(PhMA)] + carbon dioxide (CO2) + phenyl methacrylate (PhMA) and P(PhMA) + CO2 + dimethyl ether (DME) systems. The cloud-point pressure for the P(PhMA) + CO2 + PhMA system is measured with the variations of temperature, and PhMA weight fraction of 39.4, 45.8, 54.2, 59.9, and 62.1 wt %. In 62.1 wt % PhMA to the solution of P(PhMA) + carbon dioxide, the cloud-point phase behaviors are shown the typical lower critical solution temperature (LCST). In addition, the effect by cosolvents concentration for the P(PhMA) + CO2 + DME system is investigated at temperature to 453.9 K and pressure range from 52.24 to 80.86 MPa. The cloud point curve for P(PhMA) + CO2 + DME systems is shifted from LCST region to upper critical solution temperature (UCST) region according to the increase of DME concentration. We report experimental data of the PhMA + CO2 system at high pressures range from 6.24 to 24.9...

The cloud-point pressure of poly(t-butylaminoethyl methacrylate) [Poly(TBAEMA)] in various solvents such as supercritical carbon dioxide (CO2), dimethyl ether (DME) and t-butylaminoethyl methacrylate (TBAEMA) was measured to maximum pressure and temperature of 218.79MPa and 452.9 K, respectively. The phase behavior for the Poly(TBAEMA)+CO2+TBAEMA mixture was investigated according to the various contribution factors, such as pressure, temperature and concentration with TBAEMA mass fraction of 9.9 wt%, 10.4 wt%, 14.9 wt%, 24.4 wt% and 35.2 wt%. The cloud point curves for the Poly(TBAEMA)+CO2+DME (15.6-78.7 wt%) systems show the variation of the (p, T) curve from upper critical solution temperature (UCST) region to lower critical solution temperature (LCST) region as DME concentration increases. The experimental data for the CO2+TBAEMA system were reported at the broad temperature range of 313.2 K to 393.2 K and the pressure range of 3.70MPa to 20.62MPa. The CO2+TBAEMA binary system shows the type-I phase behavior with a continuous critical mixture curve, and is correlated by Peng-Robinson equation of state with the critical properties for TBAEMA obtained by Joback and Lyderson group contribution method.

In this work, we investigated the prediction of solubility (xd) of drug molecules in single- and mixed-ionic liquid (IL) solutions using the COSMO-SAC activity coefficient model. In particular, the effect of dissociation of IL on solubility is examined. The prediction accuracy is found to be 91% in xd (root-mean-square deviation in ln xd is 0.65) for a total of 442 data points with solubility ranging from 0.93 to 2.84 × 10−4 (mole fraction) and temperature ranging from 248.92 K to 488.3 K. The solubility of drug is found not sensitive to the treatment of dissociation of IL in the calculations. The method is used to determine the solubility of paracetamol in 2,624 single IL made from combination of 82 cations and 32 anions. The solubility of paracetamol can vary by 4 orders of magnitude in different ILs, indicating that this is a powerful method for screening for solvents with desired solubility power. The solubility of a drug in binary IL solution can be significantly higher or lower than those in pure IL components. For the 3,441,376 binary IL mixtures, about 8% of the mixtures exhibit higher solubility for paracetamol and 6% exhibit lower solubility. Our results indicate that mixing ILs can be a viable approach for tuning drug solubility. This article is protected by copyright. All rights reserved.

The amino acid exists in the zwitterion form with positive (amino group, − NH3+) and negative (carboxyl group, COO−) charge in water, and it is able to form the ion-pair complexes physically bonded with ions. The ion-pair complex between amino acid and ions has a strong effect on the variation of activity coefficient of amino acid in aqueous electrolyte solution. In this work, the PC-SAFT EOS combined with primitive mean spherical approximation (PM-MSA) model is applied to the 32 amino acid-electrolyte aqueous systems (a total of 1305 data points) for modeling the activity coefficients of amino acids and electrolyte in aqueous solutions. The ion-pair complex is considered as a cross-association between amino acid and ions, and this method accurately represents the activity coefficient of an amino acid and electrolyte over a wide range of concentrations. Based on the calculation of activity coefficient ratio of amino acid, the solubility of an amino acid in electrolyte-water system and density of solution are predicted, and the predicted results show qualitative agreement with experimental results. Therefore, the model proposed in this work is expected to be useful for describing activity coefficients of an electrolyte and amino acid in amino acid-electrolyte-water system.

The perturbed hard-sphere-chain-association (PHSC-AS) equation of state is applied to calculate the phase equilibrium of hydrogen bonding polymer systems. The pure parameters of polymers are estimated by regression of pressure–volume–temperature (PVT) data of pure molten-polymer. The calculation results show a good agreement with experimental data over the wide temperature (303 to 543 K) and pressure (1 to 2001 bar) range. The calculation results for vapor–liquid equilibrium (VLE) of polymer–solvent systems also show a good accuracy with ARD error of about 4% (a total of 354). The PHSC-AS model describes well the effects of various factors on vapor pressure of hydrogen-bonding polymer solution, such as temperature, solvents with different polarity (i.e., water, alcohols, acetone, amine), and the molecular weight and molecular structure of polymer. In addition, the infinite dilution weight fraction activity coefficient (WFAC) of strongly polar solvents such as water, alcohols, and acetic acid is calculated...

The separation of azeotropic mixtures is a great challenge for concentrating a desired chemical compound because it cannot be attained by a simple distillation process. Liquid-liquid extraction can be an alternative process to resolve the separation problem if an appropriate solvent is selected to effectively partition the mixture. In this work, the feasibilities of three different deep eutectic solvents (DESs) for breaking azeotropes of n-hexane and ethanol mixture were examined by means of liquid-liquid extraction. Choline chloride (ChCl) was chosen as a base compound and three hydrogen bond donors (HBDs) of levulinic acid, ethylene glycol, and malonic acid were added at their eutectic ratio to form DESs. Liquid-liquid equilibrium experiments for an azeotropic n-hexane + ethanol system were carried out to determine binodal compositions and, then, evaluate the compositions at both liquid phases at 298.2 K and atmospheric pressure by employing the prepared DESs. Refractive index, density, and viscosity at the binodal compositions were measured to provide properties required for extraction process establishment. The measured tie-lines were compared with the predicted results calculated by COSMO-SAC model. Moreover, the ability for extracting ethanol was evaluated with distribution coefficient and selectivity. It was found that the distribution coefficient and selectivity values are high enough to support a scaling-up process by a liquid–liquid extraction.

Many unique properties of ionic liquids (ILs) are closely related to the extent of dissociation (α) in solution. However, most of the existing models for ILs assume either full dissociation or full nondissociation regardless of mixture compositions. In this work, the dissociation of ILs (CA = C+ + A–) is described as a chemical reaction. Together with the predictive COSMO-SAC model, the dissociation constant can be determined based on the value of α in the pure state. Our results show that the predicted composition dependence of α is in good agreement with experiment over the entire concentration range. We further examine the prediction of a variety of thermodynamic properties and phase behaviors of IL solutions, covering high (infinite dilution activity coefficient of solvent), medium (vapor–liquid and liquid–liquid), and low (osmotic coefficient and mean ionic activity coefficient) IL concentrations (a total of 9857 data points). Our results show that the composition dependence of IL dissociation has a ...

Perturbed-hard-sphere-chain-association (PHSC-AS) equation of state, which is defined by incorporating the association term of the statistical associating fluid theory (SAFT) model into the PHSC equation of state with van der Waals-type dispersion term, is used to calculate the liquid–liquid equilibrium (LLE) for complex associating mixtures such as alcohol/alkane, water/alkane, acetic acid/alkane, alcohol/water, and carboxylic acid/water systems. In this work, the PHSC-AS models with two different chain terms have been investigated. One is the original model proposed by Song et al. [Macromolecules 1994, 27 (2), 441−448], and the other is the modified model whose chain term was replaced with that of the SAFT model. The calculated results of LLE for associating mixtures are compared with those by the purturbed-chain-SAFT (PC-SAFT) model as well. The results with PHSC-AS and PC-SAFT equation of state are in acceptable agreement with the experimental data. Despite the simple dispersion equation with van der ...

The octanol–water partition coefficient (Kow) of ionic liquids (ILs) is an important indicator for its toxicity and environment impact. In this work, the Kow is determined from the ratio of infinite dilution activity coefficient of IL in the water-rich and octanol-rich phases. In particular, the Pitzer-Debye−Huckel (PDH) model combined with the predictive COSMO-SAC model is used for calculating the activity coefficients. A root-mean square deviation of 0.75 is achieved for log Kow, or a factor of 4 in Kow, for a total of 67 ILs at ambient condition. The long-range coulomb interactions (from the DH model) contribute an almost constant value of −1.35 to log Kow, regardless of the type of IL. The change of log Kow with the molecular structure of IL is found to be dominated by the short-range attractive interactions between the IL and the solvents, including the hydrogen bonding and nonhydrogen bonding surface interactions. The combination of PDH and COSMO-SAC models provides not only the quantitative predictions of Kow of ILs and but also physical insights to the relations between Kow and the molecular structure of ILs.

In this work, a predictive method is applied to determine the vapor–liquid-hydrate three-phase equilibrium condition of methane hydrate in the presence of ionic liquids and other additives. The Peng–Robinson–Stryjek–Vera Equation of State (PRSV EOS) incorporated with the COSMO-SAC activity coefficient model through the first order modified Huron–Vidal (MHV1) mixing rule is used to evaluate the fugacities of vapor and liquid phases. A modified van der Waals and Platteeuw model is applied to describe the hydrate phase. The absolute average relative deviation in predicted temperature (AARD-T) is 0.31% (165 data points, temperature ranging from 273.6 to 291.59 K, and pressure ranging from 1.01 to 20.77 MPa). The method is further used to screen for the most effective thermodynamic inhibitors from a total of 1722 ionic liquids and 574 electrolytes (combined from 56 cations and 41 anions). The valence number of ionic species is found to be the primary factor of inhibition capability, with the higher valence lea...

We propose a new predictive approach for the calculation of properties and phase behavior of mixtures containing ionic liquids (ILs). In this method the Pitzer–Debye–Huckel (PDH) model for the long-range electrostatic interactions is combined with the COSMO-SAC model for the short-range interactions between contacting molecules. While the COSMO-SAC model alone has been shown to be accurate for vapor–liquid equilibrium (VLE) and infinite dilution activity coefficient (IDAC) of solvents in ILs, it is inaccurate for dilute IL solution properties such as the osmotic coefficient (OC) and mean ionic activity coefficient (MIAC), where long-range interactions are important. The PDH model alone is accurate for dilute IL solutions; however, it is not applicable at high IL concentrations. Here we propose a novel method for attenuating the long-range effects from the PDH model at high IL concentrations. The resultant model is found to be accurate over the whole concentration ranges of the IL solutions. We have examined this method for three versions of the COSMO-SAC model, denoted as COSMO-SAC(2007) + PDH(α), COSMO-SAC(2010) + PDH(α), and COSMO-SAC(ion,α), for mixtures involving 73 ILs formed from the combination of 20 cations and 15 anions. The absolute relative deviations (ARD) from the three models for IDAC (3552 points) are 107.89%, 165.37%, and 116.94%, respectively. The errors for VLE (1626 points) are 23.98%, 28.88%, and 22.02%, respectively. The prediction accuracy for OC (1348 points) are 40.86%, 48.10% and 24.09%, and the predicted MIAC (484 points) of ionic liquid showed a similar accuracy of about 48%. The proposed COSMO-SAC models provide prediction of properties of IL fluids with consistent accuracy over the full range of concentrations.

Chemotherapy for intracranial gliomas is hampered by limited delivery of therapeutic agents through the blood brain barrier (BBB). An optimal therapeutic agent for brain tumors would selectively cross the BBB, accumulates in the tumor tissue and be activated from an innocuous prodrug within the tumor. Here we show brain tumor-targeted delivery and therapeutic efficacy of a nanometer-sized prodrug (nanoprodrug) of camptothecin (CPT) to treat experimental glioblastoma multiforme (GBM). The CPT nanoprodrug was prepared using spontaneous nanoemulsification of a biodegradable, antioxidant CPT prodrug and α-tocopherol. The oxidized nanoprodrug was activated more efficiently than nonoxidized nanoprodrug, suggesting enhanced therapeutic efficacy in the oxidative tumor microenvironment. The in vitro imaging of U-87 MG glioma cells revealed an efficient intracellular uptake of the nanoprodrug via direct cell membrane penetration rather than via endocytosis. The in vivo study in mice demonstrated that the CPT nanoprodrug passed through the BBB and specifically accumulated in brain tumor tissue, but not in healthy brain tissue and other organs. The accumulation preferably occurred at the periphery of the tumor where cancer cells are most actively proliferating, suggesting optimal therapeutic efficacy of the nanoprodrug. The nanoprodrug was effective in treating subcutaneous and intracranial tumors. The nanoprodrug inhibited subcutaneous tumor growth more than 80% compared with control. The median survival time of mice implanted with an intracranial tumor increased from 40.5 days for control to 72.5 days for CPT nanoprodrug. This nanoprodrug approach is a versatile method for developing therapeutic nanoparticles enabling tumor-specific targeting and treatment. The nontoxic, tumor-specific targeting properties of the nanoprodrug system make it a safe, low cost, and versatile nanocarrier for pharmaceuticals, imaging agents, and diagnostic agents.

Although mechanical properties of concrete under uniaxial compression are important to design concrete structure, current design codes or other empirical equations have clear limitation on the prediction of mechanical properties. Various types of fiber-reinforced reactive powder concrete matrix were tested for making more usable and accurate estimation equations for mechanical properties for ultra high strength concrete. Investigated matrix has compressive strength ranged from 30 MPa to 200 MPa. Ultra high strength concrete was made by means of reactive powder concrete. Preventing brittle failure of this type of matrix, steel fibers were used. The volume fraction of steel fiber ranged from 0 to 2%. From the test results, steel fibers significantly increase the ductility, strength and stiffness of ultra high strength matrix. They are quantified with previously conducted researches about material properties of concrete under uniaxial loading. Applicability of estimation equations for mechanical properties of concrete was evaluated with test results of this study. From the evaluation, regression analysis was carried out, and new estimation equations were proposed. And these proposed equations were applied into stress-strain relation which was developed by previous research. Ascending part, which was affected by proposed equations of this study directly, well fitted into experimental results.

Activity coefficients and solubilities of L-Valine and L-Proline in aqueous solutions containing each of four electrolytes such as NaCl, KCl, and were measured at 298.15 K. The measurements of activity coefficients were carried out in the electrochemical cell coupled with two ion-selective electrodes (cation and anion), and the solubilities were measured by the gravimetric analysis of saturated solutions in equilibrium with the solid phase of amino acid. The measured activity coefficients of electrolytes and amino acids were correlated with the theoretical thermodynamic model presented in the previous work [Korean Chem. Eng. Res. 48(4), 519(2010)]. It was found that the activity coefficients of amino acids and electrolytes described based on the our previous model were well agreeable with experimental data. Also the experimental solubility data of L-Valine and L-Proline were successfully correlated with the thermodynamic relation mentioned in the previous work.

The purpose of this study was to prepare and characterize nanometer-sized prodrug (nanoprodrug) of camptothecin. The camptothecin prodrug was synthesized using tetraethylene glycol spacer linked via carbonate bond to camptothecin and via ester bond to alpha-lipoic acid. The nanoprodrug was prepared through the spontaneous emulsification mechanism using the mixture of camptothecin prodrug and alpha-tocopherol which served as a structural matrix. The nanoprodrug was activated readily by porcine liver esterase and, with a much slower rate, by hydrolytic degradation. Upon longterm storage, the alpha-lipoic acid moiety of the camptothecin prodrug gradually oxidized without loss of structural integrity and therapeutic efficacy. Interestingly, the hydrolytic activation was negligible before the oxidation, but was significantly accelerated after the oxidation of the alpha-lipoic acid moiety, suggesting an oxidative stimuli-responsive activation of the prodrug. The camptothecin nanoprodrug was found to possess significant inhibitory effect on the proliferation of U87-MG glioma cells with an IC(50) of 20 nM.

Perturbed-chain statistical associating fluid theory (PC-SAFT) was applied for modeling the thermodynamic properties of aqueous amino acid solutions. To account for the association phenomena of amino acids occurring in the aqueous solution, the zwitterionic forms of amino acids are assumed to be associating species with proton donor and acceptor sites. Also, in order to reduce the number of adjustable parameters of PC-SAFT equation of state (EoS) for amino acids from five to three, it is assumed that segment numbers of amino acids are linearly related with the molecular weight of amino acids, and the association volume parameters of amino acids can be set to a fixed value. Thus, 3-parameters of PC-SAFT EoS for amino acids were estimated by simultaneously fitting the activity coefficients of amino acid and densities data in the aqueous amino acid solutions. The PC-SAFT EoS with estimated 3-parameters of amino acid is found to well describe activity coefficients of amino acid and densities of the aqueous amino acid solutions. Also, this equation was used for predicting solubilities of amino acids as well as the water activities and osmotic coefficients in the aqueous amino acid solutions. The predicted values of these properties are in good agreement with the experimental data.

In this work an equation of state applicable to the system containing electrolytes has been developed by coupling the perturbed chain statistical associating fluid theory (PC-SAFT) with the primitive mean spherical approximation. The resulting electrolyte equation of state is characterized by 4 ion parameters for each of the cation and anion contained in aqueous solutions, and 4 ion specific parameters for each of six cations (Li+, Na+, K+, Rb+, Mg2+ and Ca2+) and six anions (Cl−, Br−, I−, HCO 3 − , NO 3 − and SO 4 2− ) were estimated, based upon the individual ion approach, from the fitting of experimental densities and mean ionic activity coefficients of 26 aqueous single-salt solutions at 298.15 K and 1 bar. The present equation of state with the estimated individual ion parameters has been found to satisfactorily describe not only the densities and mean ionic activity coefficients, but also osmotic coefficients and water activities of single-salt aqueous solutions. Furthermore, the present model was extended to two-salt aqueous solutions, and it has been found that thermodynamic properties such as mentioned above, of two-salt solutions, can be well predicted with the present model, without any additional adjustable parameters.

Tumor-specific targeting using achievements of nanotechnology is a mainstay of increasing efficacy of anti-tumor drugs. To improve drug targeting we covalently conjugated for the first time two different monoclonal antibodies, an anti-mouse transferrin receptor antibody and a mouse autoimmune anti-nucleosome antibody 2C5, onto the drug delivery nanoplatform, poly(beta-L-malic acid). The active anti-tumor drug components attached to the same carrier molecule were antisense oligonucleotides to vascular protein laminin-8. The resulting drug, a new Polycefin variant, was administered intravenously into glioma-bearing xenogeneic animals. The drug delivery system was targeted across mouse endothelial system by the anti-mouse transferring receptor antibody and to the tumor cell surface by the anti-nucleosome antibody 2C5. The targeting efficacies of the Polycefin variants bearing either two antibodies or each single antibody were compared in vitro and in vivo. ELISA confirmed the co-existence of two antibodies on the same nanoplatform molecule and their functional activities. Fluorescence imaging analysis after 24 h of intravenous injection demonstrated significantly higher tumor accumulation of Polycefin variants with the tandem configuration of antibodies than with single antibodies. The results suggest improved efficacy for tandem configuration of antibodies than for single configurations carried by a drug delivery vehicle.

For developing the equation of state which can be applicable to associating fluids, the Perturbed-Hard-Sphere-Chain-Association (PHSC-AS) equation of state is proposed by incorporating the association term of the SAFT model into the PHSC equation of state which has been widely used to describe phase equilibria for the fluid system containing a large molecule such as polymer. In this work, two different types of PHSC models have been examined. One is the original model proposed by Song et al., and the other is the modified model by Kim and Bae whose chain term was replaced with that of the SAFT model. As a result, two types of PHSC-AS models are obtained, and applied to the calculation of phase equilibria for the binary system containing a self-associating compound such as alcohol, amine and carboxylic acid, etc. The calculated results of vapour-liquid equilibria are in good agreement with the experimental data. The proposed models (PHSC-AS) are also compared to the PC-SAFT model.

Polymalic acid is receiving interest as a unique biopolymer of the plasmodia of mycetozoa and recently as a biogenic matrix for the synthesis of devices for drug delivery. The acellular slime mold Physarum polycephalum is characterized by two distinctive growth phases: uninucleated amoebae and multinucleated plasmodia. In adverse conditions, plasmodia reversibly transform into spherules. Only plasmodia synthesize poly(malic acid) (PMLA) and PMLA-hydrolase (polymalatase). We have performed suppression subtractive hybridization (SSH) of cDNA from amoebae and plasmodia to identify plasmodium-specific genes involved in PMLA metabolism. We found cDNA encoding a plasmodium-specific, spherulin 3a-like polypeptide, NKA48 (spherulin 3b), but no evidence for a PMLA-synthetase encoding transcript. Inhibitory RNA (RNAi)-induced knockdown of NKA48-cDNA generated a severe reduction in the level of PMLA suggesting that spherulin 3b functioned in regulating the level of PMLA. Unexpectedly, cDNA of polymalatase was not SSH-selected, suggesting its presence also in amoebae. Quantitative PCR then revealed low levels of mRNA in amoebae, high levels in plasmodia, and also low levels in spherules, in agreement with the expression under transcriptional regulation in these cells.

The naturally synchronous plasmodia of myxomycetes synthesize poly(beta-l-malic acid), which carries out cell-specific functions. In Physarum polycephalum, poly(beta-l-malate) [the salt form of poly(beta-l-malic acid)] is highly concentrated in the nuclei, repressing DNA synthetic activity of DNA polymerases by the formation of reversible complexes. To test whether this inhibitory activity is cell-cycle-dependent, purified DNA polymerase alpha of P. polycephalum was added to the nuclear extract and the activity was measured by the incorporation of [3H]thymidine 5'-monophosphate into acid precipitable nick-activated salmon testis DNA. Maximum DNA synthesis by the reporter was measured in S-phase, equivalent to a minimum of inhibitory activity. To test for the activity of endogenous DNA polymerases, DNA synthesis was followed by the highly sensitive photoaffinity labeling technique. Labeling was observed in S-phase in agreement with the minimum of the inhibitory activity. The activity was constant throughout the cell cycle when the inhibition was neutralized by the addition of spermidine hydrochloride. Also, the concentration of poly(beta-l-malate) did not vary with the phase of the cell cycle [Schmidt, A., Windisch, C. & Holler, E. (1996) Nuclear accumulation and homeostasis of the unusual polymer poly(beta-l-malate) in plasmodia of Physarum polycephalum. Eur. J. Cell Biol. 70, 373-380]. To explain the variation in the cell cycle, a periodic competition for poly(beta-l-malate) between DNA polymerases and most likely certain histones was assumed. These effectors are synthesized in S-phase. By competition they displace DNA polymerase from the complex of poly(beta-l-malate). The free polymerases, which are no longer inhibited, engage in DNA synthesis. It is speculated that poly(beta-l-malate) is active in maintaining mitotic synchrony of plasmodia by playing the mediator between the periodic synthesis of certain proteins and the catalytic competence of DNA polymerases.

The production of β-poly(L-malate) (PMLA) by non-growing microplasmodia of Physarum polycephalum was investigated. Growth was minimal in culture medium devoid of nitrogen source, but PMLA production occurred at a substantial rate. The addition of metabolic intermediates, malate, fumarate, succinate, and oxaloacetate, and the omission of hematin showed considerable growth inhibition in the presence of the nitrogen source, while PMLA production per unit biomass increased significantly. The results indicated that PMLA production was dissociated from biomass production under these conditions. The stimulating effect of carbonate on PMLA production was independent on growth. Cultivation in the absence of the nitrogen source and hematin or in the presence of the metabolites may be a useful technique for efficient PMLA production at a minimum of biomass production.

beta-Poly(L-malate) is supposed to function in the storage and transport of histones, DNA polymerases and other nuclear proteins in the giant syncytical cells (plasmodia) of myxomycetes. Here we report on the biosynthesis of [14C]beta-poly(L-malate) from injected L-[14C]malate in the plasmodium of Physarum polycephalum. The effects of KCN, arsenate, adenosine 5'-(alpha, beta-methylene)triphosphate, adenosine 5'-(beta, gamma-methylene)triphosphate, guanosine 5'-(beta, gamma-methylene)triphosphate, desulfo coenzyme A and phenylarsinoxid on beta-poly(L-malate) synthesis were studied after their coinjection with L-[14C]malate. The synthesis was not affected by KCN or desulfo coenzyme A, but was blocked by arsenate and adenosine 5'-(alpha,beta-methylene)triphosphate. The plasmodium lysate catalysed an L-malate-dependent ATP-[32P]pyrophosphate exchange, but was devoid of beta-poly(L-malate) synthetic activity under all experimental conditions tested. The results suggested an extramitochondrial synthesis of beta-poly(L-malate), involving the polymerization of beta-L-malyl-AMP. It is assumed that the lack of synthesis in the lysate is caused by the inactivation of beta-poly(L-malate) polymerase involving a cell injury kinase pathway. Because injected guanosine 5'-(beta, gamma-methylene)triphosphate blocks the synthesis, the injury signal is likely to be GTP dependent.