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Chemotherapy of human African trypanosomiasis (HAT) is unsatisfactory because only a few drugs, with serious side effects and poor efficacy, are available. As drug combination regimes often achieve greater therapeutic efficacy than monotherapies, here the trypanocidal activity of the cysteine protease inhibitor K11777 in combination with current anti-HAT drugs using bloodstream forms of Trypanosoma brucei was investigated. Isobolographic analysis was used to determine the interaction between cysteine protease inhibitors (K11777, CA-074Me and CAA0225) and anti-HAT drugs (suramin, pentamidine, melarsoprol and eflornithine). Bloodstream forms of T. brucei were incubated in culture medium containing cysteine protease inhibitors or anti-HAT drugs alone or in combination at a 1:1 fixed-dose ratio. After 48 h incubation, live cells were counted, the 50% growth inhibition values determined and combination indices calculated. The general cytotoxicity of drug combinations was evaluated with human leukaemia HL-60 cells. Combinations of K11777 with suramin, pentamidine and melarsoprol showed antagonistic effects while with eflornithine a synergistic effect was observed. Whereas eflornithine antagonises with CA-074Me, an inhibitor inactivating the targeted TbCATL only under reducing conditions, it synergises with CAA0255, an inhibitor structurally related to CA-074Me which inactivates TbCATL independently of thiols. These findings indicate an essential role of thiols for the synergistic interaction between K11777 and eflornithine. Encouragingly, the K11777/eflornithine combination displayed higher trypanocidal than cytotoxic activity. The results of this study suggest that the combination of the cysteine protease inhibitor K11777 and eflornithine display promising synergistic trypanocidal activity that warrants further investigation of the drug combination as possible alternative treatment of HAT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The water stability of iron oxide nanoparticles (NPs) is a major issue for biomedical and biological applications. This paper presents a versatile approach for preparing water-soluble iron oxide nanoparticles coated by bifunctional oligo(ethylene oxide) (OEO) chains, carrying on the one side a diazonium end group for covalent grafting at the NP surface and on the other side an iniferter group (diethyl dithiocarbamate) for initiating the growing of poly(methacrylic acid). The nanoparticles were synthesized by coprecipitation in basic media and functionalized in situ by adding the diazonium salt directly in the synthesis medium. Oligo(ethylene oxide) with various chain lengths (from one to three monomer units) was grafted at the NP surface using this approach. The length of the OEO spacer between the NP surface and the iniferter end group was found to be a critical parameter for controlling the colloidal stability of the hybrid NPs. The polymerization time was also shown to strongly influence their colloidal stability, emphasizing the interest to control the interfacial properties of the hybrids for obtaining stable dispersions in water., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Carbohydrate- and oligoethylene oxide-based surfactants behave quite differently despite the fact that they are both classes of nonionic surfactants. Intensive studies of a mixture at fixed molar ratio (1:1) of two very common sugar- and oligoethylene oxide-based surfactants, namely n-dodecyl-β-D-maltoside (β-C(12)G(2)) and n-dodecyl hexaethylene oxide (C(12)E(6)), revealed that most properties of the mixture are similar to those of the oligoethylene oxide-based surfactant. In the present work, this mixture is compared to respective "hybrid surfactants". Such hybrid surfactants are surfactants whose head group contains chemically linked carbohydrate and oligoethylene oxide units. In order to study the behaviour of this sort of compounds, we synthesised a new class of surfactants whose head group consists of one carbohydrate-like unit (myo-inositol) and three ethylene oxide units. New regiochemically defined ethoxylated inositol derivatives (referred to as C(12)I(1)E(3) and C(12)E(3)I(1) in the following) were synthesised and studied for their thermotropic and lyotropic liquid crystalline properties as well as for their surface activities. The results are compared with those of the reference systems β-C(12)G(2) and C(12)E(6), and their 1:1 mixture, respectively, and are discussed in terms of structure-property relations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study reports the unique aqueous lyotropic liquid crystal behavior of an anionic hybrid surfactant, 8F-B2ES, which has 2-[2-(butyloxy)ethyloxy]ethyl and 1H,1H,2H,2H-perfluorodecyl tails. An 8F-B2ES-analog hybrid surfactant with no oxyethylene units (8F-DeS) and a symmetric fluorinated double-tail surfactant with two 2-(1H,1H,2H,2H-perfluorohexyloxy)ethyl tails (4FEOS) were used as control surfactants in examining the effects of the oxyethylene units and of the hybrid structure on the liquid crystal behavior. Polarized microscopic observations showed the formation of a lamellar liquid crystal phase for each surfactant/water mixture at surfactant concentrations higher than 10 wt.%. In the case of the 30 wt.% 8F-B2ES/water mixture, two types of spherical aggregates were observed at temperatures higher than 40 °C: one was a typical lamella liquid crystal with a maltese cross-texture, and the other was optically isotropic. Interestingly, when the 8F-B2ES lamellar phase was cooled to below 40 °C, the lamellar aggregates were distorted and the isotropic droplets became anisotropic. As this unique liquid crystal behavior was not observed for aqueous mixtures of the control surfactants, the oxyethylene units in the hybridized hydrocarbon tail play an important role in the behavior. This study also examined the effect of the oxyethylene units on microenvironmental polarity in the hybrid surfactant bilayer via fluorescence spectral measurements of pyrene solubilized in each lamellar phase. The polarity of the 8F-B2ES bilayer at 70 °C was found to be that of a hydrocarbon surfactant lamellar phase, and increased gradually with decreasing temperature. The polarity became the same as that of hydrophilic spherical micelles below 40 °C, despite the presence of the lamellar aggregates. Since the polarity in the 8F-DeS bilayer was independent of temperature, and as low as that of a typical hydrocarbon surfactant bilayer, hydration of the 8F-B2ES oxyethylene units would increase the polarity, and then loosen the 8F-B2ES packing within the bilayer. This probably led to distortion of the lamellar aggregates., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Adsolubilisation has been defined as the incorporation to solid-water interfaces of molecules that do not adsorb spontaneously to such interfaces, but can be incorporated through an interaction with an adsorbing surfactant molecule. The aim of this work was to study the adsolubilisation of organic molecules with different hydrophobicity on collagen fibres. Hide powder collagen was treated under mild acidic aqueous conditions with an anionic surfactant, sodium dodecylbenzene sulphonate. Thereafter, five different organic molecules, i.e., benzyl alcohol, 2-naphtol, pararosaniline, hexamethylpararosaniline and nonylphenol with 10 mol ethylene oxide were separately applied to the treated collagen in order to study adsolubilisation as a function of their hydrophobicity. It was found that under acidic conditions all molecules were scarcely adsorbed or not adsorbed by the native hide powder collagen. However, all organic molecules, except benzyl alcohol, were adsolubilised if the hide powder collagen was previously treated with the anionic surfactant. The hydrophobicity of the molecules plays an important role in the adsolubilisation phenomenon with the result that the higher the hydrophobicity (nonylphenol with 10 mol ethylene oxide), the higher the adsolubilisation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We present the results of a molecular dynamics study of a set of surface-tethered S(CH2CH2O)6CH3 chains. In this study, we analyze helix formation, in addition to thermal disorder, and find that spontaneous helix formation and details of helix morphology depend on charge partitioning ascribed to oxygen and the methylene groups. The effects of varying surface coverage as well as chain-surface interaction strength indicate that a set of approximately 7/2 helical structures oriented predominantly normal to the surface are formed at near full coverage. This occurs even though thermal disorder clearly precludes a description based on the concept of a perfect crystalline monolayer. Thermal fluctuations in chain morphology in the vicinity of the terminal methyl groups lead to the exposure of oxygen to the external environment. We also find that the persistence of compact helix-containing domains at partial surface coverage results in the formation of well-defined cavities or void regions that expose the bare surface, even in the presence of strong chain-surface attractive interactions.

Shape transitions were examined with regard to the solubilization of the poorly water-soluble drug indomethacin (IMC) in the nonionic surfactants heptaethylene oxide tetradecyl (C14E7) and hexadecyl (C16E7) ethers by means of a dynamic light scattering technique. The cloud points of the pure C14E7 and C16E7 micelles ranged from 58 to 62 degrees C and from 52.1 to 55.6 degrees C, respectively, at surfactant concentrations of 1 to 10 mM. The cloud points of IMC-solubilized micelles increased by approximately 1 to 5 degrees . The sizes of the pure C14E7 micelles were 4 to 14 nm at 20 to 40 degrees C at a concentration of 2 to 20 mM. The apparent hydrodynamic radius (R happ) of pure C16E7 micelles varied with temperature and concentration. C16E7 surfactant formed small spherical micelles at 20 and 25 degrees C at concentrations below 5 mM; the size of the micelles was approximately 5 nm. On the other hand, from 30 to 40 degrees C and at a higher concentration, C16E7 formed elongated cylindrical micelles, and these elongated micelles entangled or overlapped each other. The R happ of the IMC-solubilized C14E7 micelles at 20 to 40 degrees C and of C16E7 micelles at 20 degrees C increased compared to that of pure micelles. On the other hand, the cylindrical micelles of C16E7 decreased in size and turned into spherical ones because of the hydrophobicity between the micelles caused by solubilization of IMC. This phenomenon was confirmed by transmission electron microscope (TEM) images.

Poly(ethylene oxide)-b-polymethacrylate (PEO-b-PMA), one of the double-hydrophilic block copolymers, has proved to the form nanoaggregates with poly-L-lysine (PLS). This was confirmed by turbidimetry, zeta-potential measurements, and dynamic light scattering. The nanoaggregate formation is induced by electrostatic charge neutralization of the PMA block with PLS. The properties of the aggregates are affected by PLS concentration as well PEO-b-PMA concentration. The aggregates have potential applications in biomedical science.