Model Hydrophobic Compound Research Articles

Unimolecular Nanocontainers Prepared by ROP and Subsequent ATRP from Hydroxypropylcellulose

Hydroxypropylcellulose (HPC) is used as a macroinitiator for ring-opening polymerization of e-caprolactone for the synthesis of a high molecular weight comb polymer consisting of a cellulose backbone and PCL grafts. The PCL end groups are converted into initiating sites for ATRP and chain extension of the PCL block is performed through grafting of tert-butyl acrylate to different lengths. The comb block copolymers are thereafter converted to amphiphilic polymers through deprotection of the tert-butyl group by acidic treatment, resulting in PCL-block-PAA grafts. These block copolymers are suspended in water and cross-linked using a water-soluble diamine to different attempted cross-link densities. Initial studies of the solubilization and encapsulation capacities of the amphiphilic polymers are performed using the hydrophobic model compound pyrene.

The Amphiphilic Self‐Assembling Peptide EAK16‐I as a Potential Hydrophobic Drug Carrier

It is crucial for hydrophobic drugs to be dissolved and stabilized by carriers in aqueous systems and then to be delivered into target cells. An amphiphilic self‐assembling peptide EAK16‐I (Ac‐AEAKAEAKAEAKAEAK‐NH2) is reported here to be able to stabilize a model hydrophobic compound, pyrene, in aqueous solution, resulting in the formation of colloidal suspensions. Egg phosphatidylcholine (EPC) vesicles are used as plasma membranes mimic. Fluorescence data shows that the pyrene is presented in the crystalline form when stabilized by EAK16‐I and molecularly migrates from its peptide encapsulations into the membrane bilayers of EPC vesicles when the suspension is mixed with EPC vesicles. Furthermore, the release rate can be controlled by changing peptide‐to‐pyrene ratio, and the higher ratios lead to the slower release rates due to a thicker encapsulation on the pyrene microcrystals. This demonstrates that EAK16‐I, as a promising nanobiomaterial, has the potential to be a hydrophobic compounds carrier.

Isosorbide as a novel polar head derived from renewable resources. Application to the design of short-chain amphiphiles with hydrotropic properties

The potential use of isosorbide, an original diol readily obtained by the double dehydration of sorbitol, has been investigated for the synthesis of novel amphiphilic species. The hydrophilicity of this polar head has been assessed via the synthesis and evaluation of three short-chain monoalkyl derivatives. The isosorbide polar head appears to have an unexpectedly low hydrophilicity, comparable to a diethylene oxide unit and it exhibits similar sensitivity to temperature changes. The monobutyl and monopentyl ethers of isosorbide have been found to be very efficient for the solubilisation of a model hydrophobic compound in water, giving promising hints on the use of isosorbide for the design of hydrotropic compounds.

Polymer Selection for Biphenyl Degradation in a Solid-Liquid Two-Phase Partitioning Bioreactor

The commercially available thermoplastic polymer Hytrel was selected as the delivery phase for the hydrophobic model compound biphenyl in a solid-liquid two-phase partitioning bioreactor (TPPB), and 2.9 g biphenyl could successfully be degraded in 1-L TPPBs by a pure culture of the biphenyl-degrading bacterium Burkholderia xenovorans LB400 in 50 h and by a mixed microbial consortium isolated from contaminated soil in 45 h. TPPBs consist of an aqueous cell-containing phase and an immiscible second phase that partitions toxic and/or poorly soluble substrates (in this case biphenyl) on the basis of maintaining a thermodynamic equilibrium. This paper illustrates a rational strategy for selecting a suitable solid polymeric substance for the delivery of the poorly water-soluble model compound biphenyl. The partitioning of biphenyl between the selected polymers and water was analogous to partitioning of solutes between two immiscible liquid phases. The partitioning coefficients varied between 180 for Nylon 6.6 and 11,000 for Desmopan, where the later numerical value is comparable to biphenyl partitioning coefficients between water and organic solvents. Employing a solid delivery phase enabled the utilization of a surfactant-producing microbial mixed culture, which could not be cultivated in liquid-liquid TPPBs and thereby extended the range of biocatalysts that can be employed in TPPBs.

Water‐Soluble Dendritic Core–Shell‐Type Architectures Based on Polyglycerol for Solubilization of Hydrophobic Drugs

Since many potential drugs are poorly water soluble, there is a high demand for solubilization agents. Here, we describe the synthesis of dendritic core-shell-type architectures based on hyperbranched polyglycerol for the solubilization of hydrophobic drugs. Amphiphilic macromolecules containing hydrophobic biphenyl groups in the core were synthesized in an efficient three- or four-step procedure by employing Suzuki-coupling reactions. These species were then used to solubilize the commercial drug nimodipine, a calcium antagonist used for the treatment of heart diseases and neurological deficits. Pyrene was also used as a hydrophobic model compound. It turned out that the transport properties of the dendritic polyglycerol derivatives, which are based on hydrophobic host-guest interactions, depend strongly on the degree and type of core functionalization. In the case of the multifunctional nimodipine, additional specific polymer-drug interactions could be tailored by this flexible core design, as detected by UV spectroscopy. The enhancement of solubilization increased 300-fold for nimodipine and 6000-fold for pyrene at a polymer concentration of 10 wt%. The sizes of the polymer-drug complexes were determined by both dynamic light scattering (DLS) experiments and transmission electron microscopy (TEM), and extremely well-defined aggregates with diameters of approximately 10 nm in the presence of a drug were observed. These findings together with a low critical aggregate concentration of 4x10(-6) mol L-1 indicate the controlled self-assembly of the presented amphiphilic dendritic core-shell-type architectures rather than a unimolecular transport behavior.

Casein micelle as a natural nano-capsular vehicle for nutraceuticals

Casein micelles (CM) are in effect nano-capsules created by nature to deliver nutrients, such as calcium, phosphate and protein, to the neonate. A novel approach is herein presented, to harness CM, for nano-encapsulation and stabilization of hydrophobic nutraceutical substances for enrichment of non-fat or low-fat food products. Such nano-capsules may be incorporated in dairy products without modifying their sensory properties. This study introduces new possibilities for encapsulation and delivery of sensitive health-promoting substances using natural GRAS (generally regarded as safe) ingredients. As a model hydrophobic nutraceutical compound we studied the fat-soluble vitamin D2, which is essential for calcium metabolism. A protocol for incorporation of vitamin D2 into CM was established. The encapsulation process was evaluated, and so was the protective effect of the micelles against photochemical degradation of the vitamin. We have demonstrated, for the first time, the possibility to load a nutraceutical compound into CM, utilizing the natural self-assembly tendency of bovine caseins. The vitamin was about 5.5 times more concentrated within the micelles than in the serum where it was only present bound to residual soluble caseins. Moreover, the morphology and average diameter of the re-assembled micelles were similar to those of naturally occurring CM. We have also demonstrated that the re-assembled CM can provide partial protection against UV-light-induced degradation to vitamin D2 contained in them. This study suggests that CM may be useful as nano-vehicles for entrapment, protection and delivery of sensitive hydrophobic nutraceuticals within food products.

Polycaprolactone‐b‐Poly(ethylene oxide) Biocompatible Micelles as Drug Delivery Nanocarriers: Dynamic Light Scattering and Fluorescence Experiments

AbstractSummary: Dynamic light scattering (DLS) and fluorescence experiments were carried out to study PCL44‐b‐PEO114 biocompatible micelles used as nanocarriers in drug delivery. Micelles prepared by a simple procedure (THF removal under nitrogen flow) exhibited a narrow size distribution with an average diameter of 100 nm. For micelles containing a hydrophobic model compound (pyrene) within the PCL core, a smaller average micellar size of 80 nm was observed, with a simultaneous broadening in the size distribution profile. In parallel to DLS results, fluorescence experiments showed evidence of pyrene encapsulation, and that the onset of the micellization process occurs at approximately 10/90 (v/v) THF/water mixtures in the case of PCL44‐b‐PEO114 polymer.

Effect of surfactant counterion and organic modifier on the properties of surfactant vesicles in electrokinetic chromatography

Counterion and organic modifier are two parameters in EKC that can be varied in order to obtain improved solubility, selectivity, and efficiency. The effect of changing surfactant counterion and/or organic modifier on the chromatographic and electrophoretic properties of cetyltrimethylammonium bromide (CTAB)/sodium octyl sulfate (SOS) vesicles is examined in EKC. The vesicles are prepared in a 1:3.66 cationic/ anionic mole ratio for a total surfactant concentration of 69 mM. The cationic CTAB is replaced by cetyltrimethylammonium chloride (CTAC) and the first use of CTAC/SOS vesicles is reported. The mean diameter of the CTAC/SOS vesicles is 96 nm while that of the CTAB/SOS vesicles is 85 nm. A class I modifier (2-amino-1-butanol) and a class II modifier (acetonitrile) have similar effects on the EOF, elution range, methylene selectivity, and the efficiency of the CTAB/SOS vesicles and the CTAC/SOS vesicles. Upon addition of 10% ACN, there is roughly a 10-fold increase in the efficiency of heptanophenone, a model hydrophobic compound, compared to the efficiency using unmodified vesicles. Linear free energy relationship (LFER) analysis using the Abraham solvation model is employed to characterize solute-vesicle interactions. The results suggest that organic modifier-vesicle interactions depend somewhat on the counterion.

The Influence of Water Content of Triglyceride Oils on the Solubility of Steroids

To determine if hydration of long- and medium-chain triglyceride oils (long = soybean and olive, medium = Miglyol 812) has a significant effect on the ability to solubize the model hydrophobic compounds progesterone, estradiol, and testosterone. Soybean, olive, and Miglyol 812 oils were treated in one of two ways: hydrated or desiccated (hydrated, then dried). Solubility of (3)H-labeled progesterone, estradiol, and testosterone in the triglycerides was measured by liquid scintillation counting. Both hydration state and chain length of the triglycerides were shown to have a significant influence on the solubility of steroids. Solubility of estradiol hemihydrate and testosterone monohydrate in hydrated triglycerides is decreased by about 30%-40% compared with desiccated oils. The solubility of anhydrous testosterone was decreased by hydration of the oils due to conversion to the monohydrate crystalline form. In contrast, the solubility of progesterone was insensitive to the state of hydration of all oils. Hydration of triglyceride oils caused a significant decrease in the solubility of steroids, which may form hydrates or hemihydrates. Results suggest the need for knowledge of the hydration state of triglyceride oils to be used as pharmaceutical excipients.

Transport of hydrophobic pollutants through biofilms in biofilters

Treatment of air pollutants in a biofilter requires that the compound be effectively transported from the gas phase to the organisms that reside in a biofilm that forms upon a packing material. It has been suggested that biofilms have different transport properties than water making hydrophobic pollutants have higher removal rates than predicted based on water's transport properties. The objectives of this study were to experimentally determine partition and diffusion coefficients of a model hydrophobic compound ( α-pinene) through natural and artificial biofilms and to relate these to biofilm characteristics such as solids content and the substrate (VOC) being consumed during biofilm generation. This was done by setting up bench-scale biofilters to generate biofilm to use in partitioning and transport experiments. Batch partitioning experiments were conducted that indicated that α-pinene has a higher degree of partitioning into biofilm than into water due to the presence of solids (two orders of magnitude). A diffusion cell has also been designed and built to study the partitioning from air and diffusion of α-pinene through various artificial biofilms. The average diffusion coefficient of α-pinene through agar, which has the same partitioning properties as water, was found to be 3.4×10 −6 cm 2/ s (S.D.: 1.2×10 −6 cm 2/ s, n=12 ). Diffusion cell experiments performed with α-pinene using inactivated biofilm, previously grown on methanol and α-pinene, immobilized in agar indicate that initially sorption takes place within the film but after this initial lag phase, the transport rate is not significantly different from agar indicating the ratio of the diffusion and partition coefficient of the mobile phase is the same. Therefore, at steady state we expect the transport rates of hydrophobic pollutants through biofilms to be the same as through water.

Release of Model Compounds from “Plum-Pudding”-Type Gels Composed of Microgel Particles Randomly Dispersed in a Gel Matrix

A novel gel structure called the “plum-pudding” gel was described by us previously.1 The gel was composed of randomly dispersed microgel particles (“plums”) in a conventional hydrogel network. Depending on the preparation conditions, the microgels can be incorporated into the gel as expanded networks or dense collapsed globules. Where the microgel particles exist as collapsed globules, they have the potential to act as reservoirs for hydrophobic solutes, from which the solutes are released very slowly. The release of two model hydrophobic compounds (pyrene and BODIPY) from “plum-pudding” gels composed of 50:50 BAM:NIPAM microgels embedded in NIPA gel films was investigated. The release of pyrene was found to follow Fickian diffusion, while the release of BODIPY was found to be slightly non-Fickian. Thus, we propose that by controlling the attractiveness of the microgel particles to the solutes to be released, a range of release profiles can be obtained from pure-Fickian to almost any conceivable time scale.

Self-assembling peptide as a potential carrier of hydrophobic compounds.

Microcrystals of a hydrophobic cargo were stabilized by EAK16 II, a self-assembling oligopeptide, and suspended in aqueous solution. Pyrene was used as a model hydrophobic compound. Egg phosphatidylcholine (EPC) vesicles were prepared to mimic a cell membrane. Pyrene was released from its EAK16 II coating into EPC vesicles. The excimer decay profiles were acquired. They showed that pyrene is present in the crystalline form when stabilized by EAK16 II, it is molecularly dispersed in EPC vesicles, and it is completely released from its EAK16 II coating into the membrane bilayers. The release of pyrene from the microcrystals coated with EAK16 II into the EPC membrane was followed by fluorescence as a function of time. The amount of pyrene released into the EPC vesicles at a given time was quantified using a calibration curve. The concentration of pyrene released was determined as a function of time, and the concentration-versus-time profile was fitted with one exponential. The rate of pyrene release was found to depend on the peptide-to-pyrene molecular ratio. Higher peptide-to-pyrene ratios lead to slower transfer of pyrene to the lipophilic environment. Scanning electron micrographs demonstrated that a thicker coating on the pyrene crystals results in a slower release. The data presented in this work demonstrate that the self-assembling EAK16 II can stabilize a hydrophobic cargo in aqueous solution and deliver it into a lipophilic environment, and that the rate of transfer can be adjusted by tuning the peptide-to-pyrene ratio.

Ultrafiltration of nonionic surfactants and dissolved organic matter.

A brownwater sample with a high content of humic substances (HS) was fractionated by multistage ultrafiltration (mst-UF) into five fractions with nominal molecular weights ranging from >30 to <1 kDa. Fractions were characterized with respect to molecular size distribution and structure. Size exclusion chromatography with online DOC detection revealed that mst-UF yielded fractions with decreasing Mp (molecular weight at peak maximum) and polydispersities from nominally large to small mst-UF fractions. 13C MAS NMR analysis showed that the content of carbohydrate structures decreased from the original sample toward smaller molecular weight (MW) fractions, which in turn contained more carboxylic groups and branched aliphatic structures. Specific UV absorbances (SUVA254) were highest in the >30 kDa fraction and decreased with decreasing MW. To evaluate whether separation mechanisms other than size exclusion were of importance during the fractionation, the behavior of low molecular weight model compounds (MC) with a range of polarities was studied. Recoveries decreased with increasing hydrophobicity of the MC. For selected nonylphenol ethoxylates and 4-nonylphenol the recovery correlated well with the hydrophile-lipophile balance value. The presence of dissolved organic matter (DOM) caused an additional loss of hydrophobic MC, possibly because of sorption of the compounds onto DOM fouling layers. The hydrophilic MC caffeine was recovered almost completely (85-86%) regardless of the DOM content of the model solution. It was concluded that size exclusion was the dominant fractionation mechanism for caffeine, whereas hydrophobic interactions played a major role during the mst-UF fractionation of nonpolar contaminants. For a better understanding of the behavior of polyfunctional molecules such as HS, the effect of other physicochemical properties needs to be investigated in further studies.

Effect of Hydroxypropyl β‐Cyclodextrin on Drug Solubility in Water‐Propylene Glycol Mixtures

Combined effects of cosolvency and inclusion complexation on drug solubility were studied using a model hydrophobic compound (carbamazepine) and a model hydrophilic compound (Compound S). Propylene glycol (PG) was used as the nonaqueous solvent, and deionized water was employed for the aqueous systems. Hydroxypropyl β‐cyclodextrin (HPβCD) was chosen as the complexing agent and studied at concentrations up to 28% (w/v). Complex formation constants (Kc) and solubility enhancement ratios were determined for the respective compounds in various water/PG vehicles. The data suggested that the inclusion of the compounds was most favorable when water alone was used as the vehicle. However, the combined approach of cosolvency and complexation resulted in a significant increase in the total apparent solubility of carbamazepine (the hydrophobic compound). The same was not observed with Compound S (the hydrophilic model), since PG weakened the interactions between the molecule and HPβCD, and thus, no synergistic or additive effects were observed with the combined approach of complexation and cosolvency.

Thermally responsive polymeric micellar nanoparticles self-assembled from cholesteryl end-capped random poly( N-isopropylacrylamide- co- N,N-dimethylacrylamide): synthesis, temperature-sensitivity, and morphologies

Cholesteryl end-capped thermally responsive amphiphilic polymers with two different hydrophobic/hydrophilic chain-length ratios were synthesized from the hydroxyl-terminated random poly( N-isopropylacrylamide- co- N,N-dimethylacrylamide) and cholesteryl chloroformate. The hydroxyl-terminated precursor polymers with narrow molecular weight distributions were synthesized by free-radical polymerization using 2-hydroxyethanethiol as a chain-transfer agent. The aqueous solutions of the cholesteryl end-capped copolymers exhibited reversible phase transitions at temperatures slightly above human body temperature, with the lower critical solution temperature values being 37.7 and 38.2 °C, respectively. The critical micelle concentration values of the two cholesteryl end-capped polymers were 9 and 25 mg/L, respectively. Polymeric micellar nanoparticles were prepared from the amphiphilic polymers using a dialysis method as well as a direct dissolution method. Transmission electron microscope studies showed that the micellar nanoparticles existed in different morphologies, including spherical, star-like, and cuboid shapes. Pyrene as a model hydrophobic compound could be readily encapsulated in these polymeric nanoparticles, at loading levels of 1.0 and 0.8 mg/g for the two cholesteryl end-capped polymers, respectively. The temperature sensitivity and unusual morphology of these novel polymeric nanoparticles would make an interesting drug delivery system.

Role of plasma lipoproteins in modifying the toxic effects of water-insoluble drugs: studies with cyclosporine A.

Lipoproteins are a heterogeneous population of macromolecular aggregates of lipids and proteins that are responsible for the transport of lipids through the vascular and extravascular fluids from their site of synthesis or absorption to peripheral tissues. Lipoproteins are involved in other biological processes as well, including coagulation and tissue repair, and serve as carriers of a number of hydrophobic compounds within the systemic circulation. It has been well documented that disease states (eg, AIDS, diabetes, cancer) significantly influence circulating lipoprotein content and composition. Therefore, it appears possible that changes in the lipoprotein profile would affect not only the ability of a compound to associate with lipoproteins but also the distribution of the compound within the lipoprotein subclasses. Such an effect could alter the pharmacokinetics and pharmacological action of the drug. This paper reviews the factors that influence the interaction of one model hydrophobic compound, cyclosporine A, with lipoproteins and the implications of altered plasma lipoprotein concentrations on the pharmacological behavior of this compound.

Temperature-promoted large-volume solute enrichment in column-switching miniaturized liquid chromatography: determination of an antioxidant.

A two-valve sub-ambient temperature-promoted reversed-phase packed-capillary liquid-chromatography column-switching system has been tailored for sensitive determination of hydrophobic compounds. Such compounds are not easily dissolved in solvent mixtures of non-eluting properties that traditionally are used for solute enrichment in reversed-phase liquid chromatography. Enrichment-column solute focusing of large sample volumes was promoted by use of sub-ambient temperatures only, allowing the use of sample solvents that were stronger or equal to the mobile phase solvent strength. Subsequent column switching and enrichment-column temperature increment provided efficient low-dispersion back-flushed enrichment-column solute desorption onto the analytical column, where the solute was subjected to temperature-programmed gradient action. The antioxidant, Irganox 1076 (octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) extracted from low density polyethylene with 100% acetonitrile served as a hydrophobic model compound. The mobile phase consisted of acetonitrile containing 10 mM triethylamine and formic acid, and the 0.25 mm id enrichment-column and analytical column in lengths of 27 and 250 mm, respectively, were packed with 3.5 microm Kromasil C18 particles. Sample volumes of up to 500 microL were successfully focused on the enrichment column at 5 degrees C using loading flow rates of up to 40 microL min(-1) prior to temperature programming to 90 degrees C. The concentration limit of detection of Irganox 1076 was 6 ng mL(-1) when using an injection volume of 500 microL. The within-assay precision was in the range 3.5-6.8% (n = 6) while the between-day precision was 7.5% (n = 3) relative standard deviation. The method was linear within the investigated mass range 3-100 ng (R2 = 0.9993).

Degradation of petroleum model compounds immobilized on clay by a hypersaline microbial mat.

In this study the degradation of hydrophobic petroleum model compounds (phenanthrene, pristane, octadecane and dibenzothiophene) added to a submersed hypersaline microbial mat was investigated. Montmorillonite with an artificially altered, hydrophobic surface was used as carrier material, forming an organo-clay complex (OCC) with the attached mixture of petroleum model compounds. 6 mg/cm2 OCC were applied to cyanobacterial mat pieces, containing approximately 33.3 microg/mg OCC of each compound. The degradation experiment was performed under controlled laboratory conditions and accompanied by chemical analyses by GC/GC-MS, molecular analyses by PCR and DGGE as well as functional analyses by microsensor measurements of oxygen, photosynthesis, sulfide, pH and light. All applied model compounds were degraded, but residues were still present after 18 weeks. The aromatic compounds phenanthrene (5.1 microg/mg OCC) and dibenzothiophene (4.3 microg/mg OCC) were preferentially degraded compared to the alkanes pristane (12.4 microg/mg OCC) and n-octadecane (13.4 microg/mg OCC). Metabolic changes during the degradation process could not be detected by microsensor measurements. The molecular population analyses did not reveal any significant community changes concomitant with the decrease of the petroleum model compounds. We conclude, that the pristine mats represent an intact, robust ecosystem in which the enzymatic requirements for the degradation of the applied pollutants exist. The slow degradation process did not affect the usual high internal turnover rates and did not favor a certain population in the community of the mats.

Novel membranes for simulating biological barrier transport

The preparation of a novel type of artificial membrane using microporous membranes as scaffold material is discussed in this paper. A solvent displacement technique was used to prepare supported liquid membranes having parallel water and organic solvent filled pores. These membranes can potentially be used to simulate biological barrier transport processes. Simple permeability prediction studies showed that the effects of solute molar volume and octanol–water partition coefficient on solute transport through these membranes are similar to those observed with certain biological barriers. Experimental studies carried out using model hydrophilic and hydrophobic compounds supported theoretically predicted trends.

Uptake and Bioconcentration of 2,2′,4,4′,5,5′-Hexachlorobiphenyl by Lotic Periphyton

Abstract Laboratory experiments were conducted to examine the uptake and bioconcentration of 2,2′,4,4′,5,5′-hexachlorobiphenyl (HCBP), a model hydrophobic organic compound, in lotic periphyton. The instantaneous rate of uptake and bioconcentration factor (BCF) were determined by following the time course of uptake of 14C-HCBP in periphytic communities established on glass slides. The rate of accumulation was highest in the first 3 hours, and steady state was reached within 8 days. The bioconcentration factor on a dry weight basis (BCFd) averaged 21,000. The results of a depuration experiment indicated that HCBP desorbed from periphyton, but at a much slower rate than its adsorption. The results support the hypothesis that the mechanism of uptake of HCBP in periphyton is a rapid surface sorption followed by a much slower transfer into lipids, and that sorption is largely dependent on the surface area available. The results of this study suggest that lotic periphyton provide a large surface area for adsorption and uptake of persistent hydrophobic compounds such as HCBP and, depending on the extent of grazing pressure, could greatly influence the fate and transport of these compounds in lotic systems.