Oil-water Distribution Coefficient Research Articles

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

Self-Delivering Supramolecular Nanofiber Based on Peptide-Rhein Conjugate

A peptide-drug conjugate (PDC) is a single molecule formed by one or more drug molecules that are conjugated with functional short peptides. Some specially designed PDC can construct self-delivering supramolecular nanomedicine and improve the therapeutic effect. The design and synthesis of novel PDCs with unique assembly behavior are important for the drug delivery system. Rhein is a natural product extracted from rhubarb and has extensive pharmacological properties. In the present work, we successfully synthesized a novel PDC (VKVK-rhein) based on rhein through solid-phase synthesis technology and conventional coupling chemical methods. The anthraquinone structure of rhein and the structure of the short peptide (VKVK, Val-Lys-Val-Lys) provided VKVK-rhein with special assembly properties. VKVK-rhein can be assembled into supramolecular nanofibers in water. The equilibrium solubility, oil-water distribution coefficient, zeta potential, and cell viability of VKVK-rhein were systematically studied. Our work lays a foundation for further biological application of rhein-based PDCs.

Study on the separation mechanism of solid-substrate electrospray ionization mass spectrometry.

Solid-substrate electrospray ionization mass spectrometry is an important ambient ionization technology to simplify mass spectrometry analysis. Nowadays, its separation application has been reported increasingly, however, the detailed separation mechanism is still indistinct although the chromatographic effect was reported as a possible factor. In this study, substrate-filled capillary electrospray ionization mass spectrometry was developed as an ideal model to investigate the separation mechanism using over thirty small molecules (neutral, basic, and weakly acidic) as model compounds with C18-bonded silica gel and silica gel as the substrates. The chromatographic effect was validated by the negative t-value of oil-water distribution coefficient, and the electric field effect was verified by the paired t-test (p<0.01) between the retention times at 5.5 and 4.0kV. A differential equation was proposed to quantify the compound retention under electric field. The quantitativemethodwas validated to rapidly quantify proline (31.88 μg/mL) and hydroxyproline (20.71 μg/mL) in plasma with acceptable selectivity and accuracy. In conclusion, the separation mechanism of solid-substrate electrospray ionization mass spectrometry was the combination of the chromatographic and electric field effects, which could provide theoretical guidance for the separation optimization, and also promote its applications in biological, pharmaceutical, forensic, food and environmental analyses, etc.

A Comparison of Solubility, Stability, and Bioavailability between Astilbin and Neoastilbin Isolated from Smilax glabra Rhizoma.

Astilbin and neoastilbin are two flavonoid stereoisomers. In the present study, their solubility, stability, and bioavailability were compared in a rat. The results revealed that the water solubility of astilbin and neoastilbin was 132.72 μg/mL and 217.16 μg/mL, respectively. The oil–water distribution coefficient (log P) of astilbin and neoastilbin in simulated gastric fluid (SGF) was 1.57 and 1.39, and in simulated intestinal fluid (SIF) was 1.09 and 0.98, respectively. In SIF, about 78.6% astilbin remained after 4 h of incubation at 37 °C, while this value was 88.3% for neoastilbin. Most of the degraded astilbin and neoastilbin were isomerized into their cis-trans-isomer, namely neoisoastilbin and isoastilbin, respectively, and the decomposed parts were rare. For bioavailability comparison in a rat, an HPLC method for trace amounts of astilbin and neoastilbin determination in plasma was developed, and the pretreatment of plasma was optimized. A pharmacokinetic study showed that the absolute bioavailability of astilbin and neoastilbin in a rat showed no significant difference with values of 0.30% and 0.28%, respectively.

Evaluation on redox-triggered degradation of thioether-bridged hybrid mesoporous organosilica nanoparticles

Incorporation of degradable groups such as thioether bonds can make nanoparticles susceptible to be degraded by biological redox stimulus. Few studies have paid attention to effects of different surface properties of carriers on degradation behaviors between traditional mesoporous silica carriers and hybrid organosilica carriers, caused by inserted thioether groups. In this work, colloidal mesoporous silica (CMS) and hybrid colloidal mesoporous silica (HCMS) with different contents of doped thioether bonds are constructed to compare their physicochemical properties and degradability. With the increased amounts of doped thioether bonds, specific surface areas and Zeta potentials of HCMS nanoparticles decrease. Additionally, dynamic contact angle and the oil-water distribution coefficient are combined to characterize the hydrophobicity of CMS and HCMS nanoparticles. Therefore, after incorporating thioether bonds into the structure of carriers, the degradation behavior of HCMS nanoparticles in the medium were the result of weighing the advantages of degradable thioether bonds and disadvantages of decreased specific surface area and enhanced hydrophobicity of carriers. Experimental results displayed that, in the high concentration of reductive environment, HCMS carriers with doping proper proportion of thioether groups showed the fast degradation rate due to the cleaved thioether bonds as the dominant factor. The present work breaks the common views that all thioether bonds-bridged organosilica could become excellent biodegradable carriers, providing an objective perspective to evaluate the degradability of hybrid organosilica carriers.

Enzymatic synthesis, antioxidant ability and oil-water distribution coefficient of troxerutin fatty acid esters

Abstract Troxerutin fatty acid esters were prepared using troxerutin and fatty acid vinyl esters as substrates in pyridine through enzymatic route. The structures of as-prepared compounds were identified by FT-TR, NMR, and ESI-HRMS. Using alkaline protease (≥30 mg/mL) as enzyme, maximum yields reached 58% at 3:1 (vinyl hexanoate to troxerutin) in pyridine (water content ≤1%). The yields gradually declined as chain length of acyl donors rose. The antioxidation abilities of the as-obtained compounds were confirmed by both DPPH free radical scavenging and potassium ferricyanide reduction methods. The antioxidation ability of troxerutin fatty acid esters was found lower than that of troxerutin. However, the logP values of troxerutin fatty acid esters varied from 0.15 to 1.94, suggesting that troxerutin fatty acid esters had better lipophilicity than troxerutin (logP = −2.12) when compared to their oil-water distribution coefficients. Overall, these findings look promising as reference for further development of future troxerutin.

Study on solubility of ginkgolide components with mass fraction weight coefficient method

In this study, the HPLC-ELSD method was adopted to detect the equilibrium solubility of B and A in water and different pH buffer solution, as well as their apparent oil-water partition coefficients in the noctanol-water/buffer solution. Furthermore, the mass fraction weight coefficient method was adopted to express the integrated equilibrium solubility and oil-water distribution coefficient of ginkgolide components. The direct addition method and the mass fraction weight coefficient method were compared in calculating the property value of ginkgolide components, showing that the mass fraction weight coefficient method was more scientific and reasonable. The tentative study provided ideas to property characterization of traditional Chinese medicine components, as well as basis for studies on preparations of traditional Chinese medicine components.

Equilibrium solubility of ginkgo flavonoid components in water and PBS of different pHs with mass fraction weight coefficient method

To descript the equilibrium solubility of ginkgo flavonoid components in water and PBS of different pHs. The HPLC method was adopted to determine the concentration of quercetin, kaempferol and isorhamnetin in ginkgo biloba extracts, and the equilibrium solubility of the three components in water and PBS of different pHs. Furthermore, the mass fraction weight coefficient method was adopted to express the integrated equilibrium solubility and oil-water distribution coefficient of ginkgo flavonoid components. Ginkgo flavonoid components were well dissoluble in water, with the maximum equilibrium solubility of 408.29 mg x L(-1) at pH 7.8. Therefore, it could be preliminarily predicted that ginkgo flavonoid components had higher application value, and could provide guiding basis for further development of preparations. By comparing the results of the direct addition method and the mass fraction weight coefficient method, we found that the mass fraction weight coefficient method was more scientific and reasonable. The tentative study could provide ideas to property characterization of traditional Chinese medicine components.

Preparation of multivariant-phospholipid complex of Ginkgo biloba extract

To prepare Ginkgo biloba extract multivariant-phospholipid complex(MGBP) and improve the vitro dissolution of ginkgo total flavonoids by adding another water-soluble carrier in phospholipid complex. MGBP was prepared using solvent evaporation method with Poloxamer-188 as the carrier and the multivariant complex was analyzed by DSC and X-diffraction technique. The physicochemical properties of the MGBP we also studied, including apparent oil-water distribution coefficients in different pH aqueous solution and its release in vitro. The in vitro dissolution of ginkgo total flavonoids was significantly increased while the apparent oil-water distribution coefficient was improved after been made into multivariant-phospholipid complex. The preparation technology of MGBP is simple and economic. MGBP can significantly increase the vitro dissolution of ginkgo total flavonoids and improve oil-water distribution coefficients, which can be the reference for the bioavailability in vivo in the further researches.

Assessment of Drug Release from Oil Depot Formulations Using an In Vitro Model—Potential Applicability in Accelerated Release Testing

In vitro drug release and transport rates from oil depot formulations under nonsink conditions have been investigated in the rotating dialysis cell model. Eight model drug compounds and eight oil vehicle compositions were used for the releaseexperiments. The experimentally obtained apparent first-order rate constants related to the drug appearance in the acceptor phase after initial instillation of a drug-containing oil solution were found to be in excellent agreement with the rate constants obtained from a theoretically derived expression. It was observed that the drug oil-water distribution coefficient was the key parameter influencing the release characteristics. As compared with ketoprofen, flurbiprofen exhibited a higher affinity for the oil, resulting in a significantly lower and more slowly decreasing drug concentrations in the aqueous donor compartment. Release profiles for prilocaine and the more lipophilic agent bupivacaine after incorporation of both drugs in fractionated coconut oil were characterized by a fast release of prilocaine, whereas bupivacaine was liberated much slower to the acceptor phase. The high oil-buffer interfacial area generated in vitro by rotation of the donor cell tends to overestimate release rates in comparison to those expected in vivo, for example, after intra-articular administration of oil solutions. The present in vitro method may constitute a valuable tool in accelerated in vitro release testing of parenteral oil depot formulations in areas comprising formulation design and product quality control.

Molecular Interactions in Lipophilic Environments Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

The description and understanding of absorption and distribution of potential new drug compounds in the organism is of paramount importance for the successful development of new drugs. However, the currently used physical chemical parameters such as oil-water distribution coefficients and ionization constants frequently fall short when it comes to a detailed description of the highly heterogeneous environments of both lipophilic and hydrophilic characters through which the drug compound passes. In this work, a new procedure based on electrochemistry at the interface between immiscible electrolyte solutions for addressing drug compound-ligand interactions in lipophilic environments as well as nonspecific ligand effects on distribution behavior has been developed. An attractive feature of the method is that it can simultaneously provide data for oil-water partition coefficients and ionization constants. The new procedure is demonstrated using five drug compounds with different physical chemical parameters and cholesterol as the oil-phase ligand. The use of ligand shift ion partition diagrams in the data presentation allows a quick visualization and comparison of a series of related drug compounds.

Oil Is a Sedimentary Supersorbent for Polychlorinated Biphenyls

The often-observed enhanced sorption of hydrophobic organic chemicals (HOCs) to sediments is frequently attributed to the presence of soot and soot-like materials. However, sediments may contain other hydrophobic phases, such as weathered oil residues. Previous experiments have shown that these residues can be efficient sorbents for certain PAHs. In this study we investigated sorption of PCBs to sediments contaminated with different concentrations and types of oils, and from that derived oil-water distribution coefficients (Koil). Sorption of PCBs to both fresh and weathered oils was proportional to sorbate hydrophobicity, and no effects of PCB planarity were observed. Furthermore, the experiments demonstrated that different oils sorbed PCBs similarly and extensively (Koil up to 108.3 for PCB 169), and that weathering caused an almost 2-fold increase in sorption of the lower chlorinated PCBs. Koil values indicated that at the PCB equilibrium concentrations tested (pg-ng/L range), for many congeners weathered oil is a stronger sorbent than pure soot and soot-like materials. Due to attenuation of adsorption to the latter materials in sediments (caused by competitive adsorption with organic matter), sedimentary weathered oil will therefore, if present as a separate phase, defeat sedimentary soot, coal, and charcoal as PCB sorbent in most cases. Consequently, weathered oil probably is the ultimate sedimentary sorbent for PCBs and should be included in HOC fate models.

Estimation of plasmalemma conductivity to ascorbic acid in intact leaves exposed to ozone

To establish the capacity of the leaf mesophyll plasmalemma of Phaseolus vulgaris L. to supply ascorbate (ASC) into the cell wall by simple diffusion, a method for calculating plasmalemma diffusional conductivity to ascorbic acid (AA) in intact leaves was evaluated. The core of the approach is that in the presence of a sink for ascorbate in the cell wall, cell wall total ascorbic acid concentration [TAA]cw (=[ASC]cw+[AA]cw) reaches zero at some positive whole-leaf total ascorbic acid concentration [TAA]l. It is shown that [TAA]l at [TAA]cw=0 is proportional to the sink for ASC in the cell wall and the reciprocal of plasmalemma conductivity. The predicted proportional relationship between [TAA]cw and [TAA]l was confirmed by decreasing TAA levels in leaves through predarkening. Furthermore, increasing the sink intensity for ASC in the cell wall by the acute exposure of leaves to 450 nmol ozone mol−1 during re-illumination, [TAA]cw reached zero at 2.7-fold higher [TAA]l than without ozone, and the slope of the relationship increased twofold. Plasmalemma diffusional conductivities to AA of 2.9×10−6 and 1.8×10−6 m s−1, needed to maintain [TAA]cw at the observed level, were calculated from the increase in [TAA]l at [TAA]cw=0 and from the two different estimates of the sink for ASC. A value of 1.3×10−6 m s−1 was calculated on the basis of the oil-water distribution coefficient for TAA. It is concluded that the demand for ASC in the mesophyll cell wall of the investigated leaves could be met by simple diffusion of AA through the plasmalemma. From the measured increase in the slope of the relationship [TAA]cw versus [TAA]l, an increase in the cell wall pH of 0.3 units was estimated under the influence of ozone.

The Absorption of Organomercurial Compounds from the Vaginal Route of the Rabbits. I. Comparative Study on the Effect of Suppository Vehicles on the Absorption of ω-Ethylmercurithio-n-undecanoic Acid, Phenylmercuric Acetate and Ethylmercuric Chloride after Single Dose Administration.

Absorption rates of three kinds of organomercurial compounds from the rabbit's vagina were studied in refference to suppository vehicles. Several types of emulsion base and Carbowax 2000 were employed as vehicles. The compounds were labelled with isotope Hg203 and the blood concentration was chronologically determined after a single vaginal administration of suppository. Modifications of the composition of emulsion vehicle resulted in some changes of an actual absorption rate for phenylmercuric acetate, because of the replacement reaction of the mercurial in the vehicle. No significant differences were observed of the influences of the type and phase ratio of emulsion vehicle on the absorption rate. When Carbowax 2000 was used as vehicle, phenylmercuric acetate showed a higher blood level than that of ω-ethylmercurithio-n-undecanoic acid or ethylmercuric chloride. It was concluded that the rate of absorption of mercurial compounds contained in suppository vehicle through rabbit's vagina was related to the water solubility and oil-water distribution coefficient of the compounds employed.

Chromatographic Transport of Reverse-Wetting Agents and Its Effect on Oil Displacement in Porous Media

Published in Petroleum Transactions, AIME, Volume 219, 1960, pages 150–157. Abstract A study of the effect upon oil recovery from an unconsolidated porous medium of chromatographic transport of selected reverse-wetting additives during water displacement is described. Flow tests were performed on hydrocarbon oil-saturated sand columns (containing connate water) into which small volumes of short-chain aliphatic amine solutions were introduced during water flooding. Concurrently, measurements of oil-silica contact angles, oil-water interfacial tensions and oil-water distribution coefficients were measured as a function of additive concentration. Certain treatments were found to cause a slight reduction in oil recovery, while others produced a significant increase (up to 50 per cent of the normal irreducible minimum oil saturation). Recovery efficiency was correlated most satisfactorily with the maximum degree of reverse wetting produced during additive transport; conditions which resulted in only mild oil wettability of the sand reduced recovery, while those favoring strong oil wetting increased recovery. A mechanism of reverse-wetting additive action during chromatographic transport is developed which ascribes the results to transient changes in oil-solid contact angle during flow, with consequent release of oil trapped by capillary forces. implications of these observations with regard to improved waterflood efficiencies are discussed. Introduction The need for finding improved methods of oil production is amply illustrated by the large volume of oil considered economically unrecoverable by existing production practice. Water flooding has long been an excellent method of secondary recovery. However, even in those areas of a formation which are well swept by a water flood, 20 per cent or more of the oil remains trapped within the formation and is not recovered. This trapping of oil within the pores of the rock structure results primarily from interfacial forces. If these interfacial forces were altered, it is possible that the trapped oil could be released and recovered.

STIMULATION OF TARSAL RECEPTORS OF THE BLOWFLY BY ALIPHATIC ALDEHYDES AND KETONES

Rejection of eight aldehydes, eight ketones, five secondary alcohols, and 3-pentanol has been studied in the blowfly Phormia regina Meigen. The data agree with results previously reported for normal alcohols and several series of glycols in showing a logarithmic increase in stimulating effect with increasing chain length. The order of increasing effectiveness among the different species of compounds thus far investigated is the following: polyglycols, diols, secondary alcohols, iso-alcohols, normal alcohols, ketones, iso-aldehydes, normal aldehydes. Curves relating the logarithms of threshold concentration to the logarithms of chain length for diols, alcohols, aldehydes, and ketones show inflections in the 3 to 6 carbon range. Above and below the region of inflection the curves are nearly rectilinear. The slopes for the upper limbs (smaller molecules) are of the order of -2; for the lower limbs, about -10. Comparisons of the threshold data with numerical values for molecular weights, molecular areas and volumes, oil-water distribution coefficients, activity coefficients, standard free energies, vapor pressures, boiling points, melting points, dipole moments, dielectric constants, and degree of association are discussed briefly, and it is concluded that none of the comparisons serves to bring the data from the several series and from the two portions of each series into a single homogeneous system. A qualitative comparison with water solubilities shows fewer discrepancies. It is suggested that the existence of a combination of aqueous and lipoid phases at the receptor surface would fit best with what is presently known about the relationship between chemical structure and stimulating effect in contact chemoreception. In this hypothesis the smaller and more highly water-soluble compounds are envisaged as gaining access to the receptors partly through the aqueous phase, the larger molecules predominantly through the lipoid phase.

Extracellular and Intracellular Hydrogen Ion Concentration in Relation to Anesthetic Effects of Barbituric Acid Derivatives

1. Certain theoretical considerations have been presented in an attempt to interpret the gradations in anesthetic effect which are exerted by substituted barbituric acids on fertilized eggs and larvae of Arbacia punctulata at varying levels of extracellular and intracellular pH. 2. The apparent dissociation constants at an ionic strength equivalent to that of sea water are presented for 30 substituted barbituric acids. 3. For each of the substituted barbituric acids investigated it is found that the extracellular concentrations of undissociated molecules required to produce a 50 per cent reduction in the rate of cell division of fertilized Arbacia eggs is independent of the extracellular pH. A similar result is obtained for the action of two barbituric acids on the movement of Arbacia larvae. These observations indicate that the barbiturates penetrate the fertilized eggs and larvae of Arbacia only in the form of undissociated molecules. 4. For each of two representative barbituric acids investigated it is found that the extracellular concentration of undissociated molecules required to produce a 50 per cent reduction in the rate of cell division of fertilized Arbacia eggs is not affected by a decrease in the intracellular pH. For each of three representative barbituric acids investigated it is found that the extracellular concentration of undissociated molecules required to produce a 50 per cent reduction in the rate of cell division is also not affected by an increase in the intracellular pH. These observations indicate that it is the barbituric acid molecule and not the barbiturate anion which is active inside the cell in producing the anesthetic effect; thus, the barbiturates are to be classified with non-ionizable anesthetics like the ethers and alcohols in respect to their mechanism of action. 5. The extracellular concentrations of undissociated molecules (which are nearly equivalent to the respective intracellular concentrations of undissociated molecules) required to produce a 50 per cent reduction in the rate of cell division of fertilized Arbacia eggs have been measured for 30 barbituric acids containing various substituents in the 1 and 5 positions of the molecule. These required molecule concentrations vary from 0.72 x l0–4 M for 5-ethyl-5-(β-ethylhexyl) barbituric acid up to 125 x 10–4 M for 5,5-diethyl barbituric acid. 6. It is observed that there is a partial, but incomplete, parallel between the order of decreasing anesthetic effectiveness, the order of decreasing oil-water distribution coefficients, and the order of increasing solubility in water.

Absorption of Drugs Through the Oral Mucosa. III. Fat-Water Solubility Coefficient of Alkaloids

It has been shown that the absorption of drugs from the mouth is strictly a selective process.1,2 With even a closely related group of drugs, such as the common alkaloids, marked differences are exhibited by the individual members. Apomorphine, for instance, can be effectively administered by simple sublingual application, whereas morphine is very poorly absorbed. The diacetyl derivative of morphine is absorbed fairly well, whereas the monomethyl derivative is absorbed very poorly. Since all 4 of these drugs are closely related both chemically and pharmacologically, the explanation for this phenomenon of selectivity might reasonably be expected to depend on physical differences. The most prominent suggestion is that of a correlation with the oil-water distribution coefficient. This relationship has been extensively developed for other problems of cell permeability,3,4 and also has been described as being the decisive factor in absorption through the oral mucosa.5 However, for this latter aspect of the cor...

Influence of (H+) Concentration on the Anesthetic Value of a Series of General and Local Anesthetics and Hypnotics

The purpose of this investigation was to determine whether any differences were to be observed in the relative anesthetic effects over widely different pH ranges, comparing a series of general anesthetics with a series of local anesthetics and a series of hypnotics. Alcohols such as allyl and isoamyl, and also general anesthetics such as chloroform, ether, chloretone, etc., do not form salts and consequently their distribution between oil and water is not markedly changed by a change in the (H+) concentration of the water phase.Local anesthetics like neothesin, cocaine and butyn are lipo-soluble organic bases with relatively low solubility as free bases in water, but in the presence of acids they form water-soluble salts. Consequently the oil-water distribution coefficient shifts from a high oil-solubility and low water-solubility on the basic side, to a low oil-solubility and high water-solubility on the acid side.In the case of the barbituric acid hypnotics exactly the reverse relation is found. The bar...