Respective Critical Micelle Concentrations Research Articles

Unraveling How Antimicrobial Lipid Mixtures Disrupt Virus-Mimicking Lipid Vesicles: A QCM-D Study.

Single-chain lipid amphiphiles such as fatty acids and monoglycerides are promising antimicrobial alternatives to replace industrial surfactants for membrane-enveloped pathogen inhibition. Biomimetic lipid membrane platforms in combination with label-free biosensing techniques offer a promising route to compare the membrane-disruptive properties of different fatty acids and monoglycerides individually and within mixtures. Until recently, most related studies have utilized planar model membrane platforms, and there is an outstanding need to investigate how antimicrobial lipid mixtures disrupt curved model membrane platforms such as intact vesicle adlayers that are within the size range of membrane-enveloped virus particles. This need is especially evident because certain surfactants that completely disrupt planar/low-curvature membranes are appreciably less active against high-curvature membranes. Herein, we conducted quartz crystal microbalance-dissipation (QCM-D) measurements to investigate the membrane-disruptive properties of glycerol monolaurate (GML) monoglyceride and lauric acid (LA) fatty acid mixtures to rupture high-curvature, ~75 nm diameter lipid vesicle adlayers. We identified that the vesicle rupture activity of GML/LA mixtures mainly occurred above the respective critical micelle concentration (CMC) of each mixture, and that 25/75 mol% GML/LA micelles exhibited the greatest degree of vesicle rupture activity with ~100% efficiency that exceeded the rupture activity of other tested mixtures, individual compounds, and past reported values with industrial surfactants. Importantly, 25/75 GML/LA micelles outperformed 50/50 GML/LA micelles, which were previously reported to have the greatest membrane-disruptive activity towards planar model membranes. We discuss the mechanistic principles behind how antimicrobial lipid engineering can influence membrane-disruptive activity in terms of optimizing the balance between competitive membrane remodeling processes and inducing anisotropic vs. isotropic spontaneous curvature in lipid membrane systems.

Membrane-Disruptive Effects of Fatty Acid and Monoglyceride Mitigants on E. coli Bacteria-Derived Tethered Lipid Bilayers.

We report electrochemical impedance spectroscopy measurements to characterize the membrane-disruptive properties of medium-chain fatty acid and monoglyceride mitigants interacting with tethered bilayer lipid membrane (tBLM) platforms composed of E. coli bacterial lipid extracts. The tested mitigants included capric acid (CA) and monocaprin (MC) with 10-carbon long hydrocarbon chains, and lauric acid (LA) and glycerol monolaurate (GML) with 12-carbon long hydrocarbon chains. All four mitigants disrupted E. coli tBLM platforms above their respective critical micelle concentration (CMC) values; however, there were marked differences in the extent of membrane disruption. In general, CA and MC caused larger changes in ionic permeability and structural damage, whereas the membrane-disruptive effects of LA and GML were appreciably smaller. Importantly, the distinct magnitudes of permeability changes agreed well with the known antibacterial activity levels of the different mitigants against E. coli, whereby CA and MC are inhibitory and LA and GML are non-inhibitory. Mechanistic insights obtained from the EIS data help to rationalize why CA and MC are more effective than LA and GML at disrupting E. coli membranes, and these measurement capabilities support the potential of utilizing bacterial lipid-derived tethered lipid bilayers for predictive assessment of antibacterial drug candidates and mitigants.

Micellization of a cationic and an anionic surfactant in the presence of diphenylcarbazide in aqueous media and the effect of micelle surface charge on the complexation of the solubilised ligand with metal ions

ABSTRACT In the present study, we carried out conductometric and surface tension analyses to report the critical micelle concentration (CMC) of tetradecyltrimethyl ammonium bromide (TTAB) and sodium dodecyl sulphate (SDS) as a function of the concentration of a diphenylcarbazide (DPC). It is found that the micellization of TTAB becomes unfavourable while that of SDS becomes favourable in the presence of DPC. This indicates a substantial difference in the mutual interaction of the sparingly soluble ligand with the cationic and the anionic surfactants. The complexation ability of the solubilised DPC with hydrated Zn(II) and Cd(II) ions at varying concentrations of the cationic and anionic surfactants was studied by UV–Vis spectral analyses. With increasing the concentration of both surfactants up to their respective CMC values, the absorbance of the metal–DPC complex increases. However, the absorbance of the complex in TTAB micelles sharply decreases, showing almost zero values beyond the CMC, but that in SDS remains almost steady with increasing the concentration of the surfactant, as evidenced from the visible spectra.

Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies.

Antimicrobial fatty acids derived from natural sources and renewable feedstocks are promising surface-active substances with a wide range of applications. Their ability to target bacterial membrane in multiple mechanisms offers a promising antimicrobial approach for combating bacterial infections and preventing the development of drug-resistant strains, and it provides a sustainable strategy that aligns with growing environmental awareness compared to their synthetic counterparts. However, the interaction and destabilization of bacterial cell membranes by these amphiphilic compounds are not yet fully understood. Here, we investigated the concentration-dependent and time-dependent membrane interaction between long-chain unsaturated fatty acids-linolenic acid (LNA, C18:3), linoleic (LLA, C18:2), and oleic acid (OA, C18:1)-and the supported lipid bilayers (SLBs) using quartz crystal microbalance-dissipation (QCM-D) and fluorescence microscopy. We first determined the critical micelle concentration (CMC) of each compound using a fluorescence spectrophotometer and monitored the membrane interaction in real time following fatty acid treatment, whereby all micellar fatty acids elicited membrane-active behavior primarily above their respective CMC values. Specifically, LNA and LLA, which have higher degrees of unsaturation and CMC values of 160 µM and 60 µM, respectively, caused significant changes in the membrane with net |Δf| shifts of 23.2 ± 0.8 Hz and 21.4 ± 0.6 Hz and ΔD shifts of 5.2 ± 0.5 × 10-6 and 7.4 ± 0.5 × 10-6. On the other hand, OA, with the lowest unsaturation degree and CMC value of 20 µM, produced relatively less membrane change with a net |Δf| shift of 14.6 ± 2.2 Hz and ΔD shift of 8.8 ± 0.2 × 10-6. Both LNA and LLA required higher concentrations than OA to initiate membrane remodeling as their CMC values increased with the degree of unsaturation. Upon incubating with fluorescence-labeled model membranes, the fatty acids induced tubular morphological changes at concentrations above CMC. Taken together, our findings highlight the critical role of self-aggregation properties and the degree of unsaturated bonds in unsaturated long-chain fatty acids upon modulating membrane destabilization, suggesting potential applications in developing sustainable and effective antimicrobial strategies.

Tethered Bilayer Lipid Membrane Platform for Screening Triton X-100 Detergent Replacements by Electrochemical Impedance Spectroscopy

In light of regulatory considerations, there are ongoing efforts to identify Triton X-100 (TX-100) detergent alternatives for use in the biological manufacturing industry to mitigate membrane-enveloped pathogen contamination. Until now, the efficacy of antimicrobial detergent candidates to replace TX-100 has been tested regarding pathogen inhibition in endpoint biological assays or probing lipid membrane disruption in real-time biophysical testing platforms. The latter approach has proven especially useful to test compound potency and mechanism of action, however, existing analytical approaches have been limited to studying indirect effects of lipid membrane disruption such as membrane morphological changes. A direct readout of lipid membrane disruption by TX-100 detergent alternatives would be more practical to obtain biologically relevant information to guide compound discovery and optimization. Herein, we report the use of electrochemical impedance spectroscopy (EIS) to investigate how TX-100 and selected replacement candidates-Simulsol SL 11W (Simulsol) and cetyltrimethyl ammonium bromide (CTAB)-affect the ionic permeability of tethered bilayer lipid membrane (tBLM) platforms. The EIS results revealed that all three detergents exhibited dose-dependent effects mainly above their respective critical micelle concentration (CMC) values while displaying distinct membrane-disruptive behaviors. TX-100 caused irreversible membrane disruption leading to complete solubilization, whereas Simulsol caused reversible membrane disruption and CTAB induced irreversible, partial membrane defect formation. These findings establish that the EIS technique is useful for screening the membrane-disruptive behaviors of TX-100 detergent alternatives with multiplex formatting possibilities, rapid response, and quantitative readouts relevant to antimicrobial functions.

Mechanistic Evaluation of Antimicrobial Lipid Interactions with Tethered Lipid Bilayers by Electrochemical Impedance Spectroscopy

There is extensive interest in developing real-time biosensing strategies to characterize the membrane-disruptive properties of antimicrobial lipids and surfactants. Currently used biosensing strategies mainly focus on tracking membrane morphological changes such as budding and tubule formation, while there is an outstanding need to develop a label-free biosensing strategy to directly evaluate the molecular-level mechanistic details by which antimicrobial lipids and surfactants disrupt lipid membranes. Herein, using electrochemical impedance spectroscopy (EIS), we conducted label-free biosensing measurements to track the real-time interactions between three representative compounds—glycerol monolaurate (GML), lauric acid (LA), and sodium dodecyl sulfate (SDS)—and a tethered bilayer lipid membrane (tBLM) platform. The EIS measurements verified that all three compounds are mainly active above their respective critical micelle concentration (CMC) values, while also revealing that GML induces irreversible membrane damage whereas the membrane-disruptive effects of LA are largely reversible. In addition, SDS micelles caused membrane solubilization, while SDS monomers still caused membrane defect formation, shedding light on how antimicrobial lipids and surfactants can be active in, not only micellar form, but also as monomers in some cases. These findings expand our mechanistic knowledge of how antimicrobial lipids and surfactants disrupt lipid membranes and demonstrate the analytical merits of utilizing the EIS sensing approach to comparatively evaluate membrane-disruptive antimicrobial compounds.

Supported Lipid Bilayer Platform for Characterizing the Membrane-Disruptive Behaviors of Triton X-100 and Potential Detergent Replacements.

Triton X-100 (TX-100) is a widely used detergent to prevent viral contamination of manufactured biologicals and biopharmaceuticals, and acts by disrupting membrane-enveloped virus particles. However, environmental concerns about ecotoxic byproducts are leading to TX-100 phase out and there is an outstanding need to identify functionally equivalent detergents that can potentially replace TX-100. To date, a few detergent candidates have been identified based on viral inactivation studies, while direct mechanistic comparison of TX-100 and potential replacements from a biophysical interaction perspective is warranted. Herein, we employed a supported lipid bilayer (SLB) platform to comparatively evaluate the membrane-disruptive properties of TX-100 and a potential replacement, Simulsol SL 11W (SL-11W), and identified key mechanistic differences in terms of how the two detergents interact with phospholipid membranes. Quartz crystal microbalance-dissipation (QCM-D) measurements revealed that TX-100 was more potent and induced rapid, irreversible, and complete membrane solubilization, whereas SL-11W caused more gradual, reversible membrane budding and did not induce extensive membrane solubilization. The results further demonstrated that TX-100 and SL-11W both exhibit concentration-dependent interaction behaviors and were only active at or above their respective critical micelle concentration (CMC) values. Collectively, our findings demonstrate that TX-100 and SL-11W have distinct membrane-disruptive effects in terms of potency, mechanism of action, and interaction kinetics, and the SLB platform approach can support the development of biophysical assays to efficiently test potential TX-100 replacements.

Bioprospecting of indigenous biosurfactant-producing oleophilic bacteria for green remediation: an eco-sustainable approach for the management of petroleum contaminated soil.

In the present study, the efficiency of four different strains of Pseudomonas aeruginosa and their biosurfactants in the bioremediation process were investigated. The strains were found to be capable of metabolizing a wide range of hydrocarbons (HCs) with preference for high molecular weight aliphatic (ALP) over aromatic (ARO) compounds. After treating with individual bacteria and 11 different consortia, the residual crude oils were quantified and qualitatively analyzed. The bacterial strains degraded ALP, ARO, and nitrogen, sulphur, oxygen (NSO) containing fractions of the crude oil by 73-67.5, 31.8-12.3 and 14.7-7.3%, respectively. Additionally, the viscosity of the residual crude oil reduced from 48.7 to 34.6-39mPas. Further, consortium designated as 7 and 11 improved the degradation of ALP, ARO, and NSO HCs portions by 80.4-78.6, 42.7-42.4 and 21.6-19.2%, respectively. Moreover, addition of biosurfactant further increased the degradation performance of consortia by 81.6-80.7, 43.8-42.6 and 22.5-20.7%, respectively. Gas chromatographic analysis confirmed the ability of the individual strains and their consortium to degrade various fractions of crude oil. Experiments with biosurfactants revealed that polyaromatic hydrocarbons (PAHs) are more soluble in the presence of biosurfactants. Phenanthrene had the highest solubility among the tested PAHs, which further increased as biosurfactant doses raised above their respective critical micelle concentrations (CMC). Furthermore, biosurfactants were able to recover 73.5-63.4% of residual oil from the sludge within their respective CMCs. Hence, selected surfactant-producing bacteria and their consortium could be useful in developing a greener and eco-sustainable way for removing crude oil pollutants from soil.

Insights on the morphology of air-assisted breakup of urea-water-solution sprays for varying surface tension

The efficacy of NOx reduction in diesel engines is mainly dependent on how uniformly urea-water solutions (UWS) are dispersed onto the catalyst surface of the Selective Catalytic Reduction (SCR) systems. The urea-based SCR systems also suffer drawbacks due to the formation of urea deposits onto the walls of after-treatment devices due to poor atomization characteristics of UWS. In this work, the impact of lowering the surface tension of UWS on the morphology of UWS sprays was explored using high-speed shadowgraph imaging techniques. The surface tension of UWS was lowered by adding surfactants; two surfactants viz., Sodium Dodecyl Sulfate (SDS) and Dodecyl-Dimethyl-Amine-oxide (DDA) were considered in this investigation. The surface tension of UWS was reduced to a maximum from 73.7 to 30.2 mN/m and 39.8 mN/m with the addition of DDA and SDS respectively at 75% of its respective Critical Micelle Concentration (CMC) in UWS. Even at a very low-pressure difference of 500 mbar of co-flowing air, the surfactant-added UWS tends to break-up relatively closer to the nozzle tip due to flapping-induced bag breakup, which improved its drop-size distribution. Under a relatively higher pressure difference of 2000 mbar of co-flow atomizing air, the liquid breakup was mostly due to surface stripping in surfactant-added UWS sprays that generated a large number of fine droplets. The image analyses of sprays were performed at far downstream locations from the nozzle to quantify the variations of their droplet-sizes caused by varying the surface tension of UWS. The surfactants added UWS sprays revealed a considerably narrower drop-size distribution by up to 43% compared to UWS sprays under high-pressure conditions, and this was due to a combination of flapping-induced bag breakup, surface stripping and secondary atomization of big droplets caused by reducing the surface tension of UWS. Reducing the surface tension of UWS has the potential to improve NOx reduction in SCR systems due to the reduction in droplet sizes of UWS sprays and also to reduce the formation of urea deposits.

Abnormal behaviors in the calibration curves of liquid chromatography-tandem mass spectrometry occurring in the quantitative analysis of surfactants near critical micelle concentrations.

Surfactants, including quaternary ammonium compounds, are widely used in daily life as part of consumer chemical products and, more recently, in the shale oil industry. Because of their unique amphiphilic properties, surfactants form micelles at concentrations above a certain threshold known as the critical micelle concentration (CMC). A previous electrospray ionization mass spectrometry studies conducted by Siuzdak et al. and others presented indirect evidence regarding micelle formation. Herein, we have used liquid chromatography-tandem mass spectrometry to explore how such micelle formations affect the quantitative analysis of surfactants. Results reveal abnormal behaviors in the calibration plots of a few selected anionic and cationic surfactants, such as sodium decyl sulfate (SDeS), sodium dodecyl sulfate (SDS), myristyltrimethylammonium bromide (MTAB), and benzyldimethyloctadecylammonium chloride (BAC-18). At concentrations close to the respective CMCs of these surfactants, the calibration plot for MTAB flattened, whereas the slopes of the calibration plots for SDeS, SDS, and BAC-18 suddenly changed. These abnormal behaviors can be related to micelle formation. From a practical perspective, the above observations suggest that in the quantitative analysis of surfactants, high micelle concentrations close to the CMC should be avoided to obtain accurate surfactant measurements.

Novel sodium alkyl-1,3-disulfates, anionic biosurfactants produced from microbial polyesters

A sodium alkyl disulfate mixture (SADM) synthesised from microbially produced 3-hydroxy fatty acids methyl esters (HFAMEs), showed 13-fold surface tension decrease when compared with the reference surfactant sodium dodecyl sulfate (SDS). Polyhydroxyalkanoates, accumulated by bacteria intracellularly when supplied with a mixture of fatty acids derived from hydrolysed rapeseed oil, were isolated, depolymerised and methylated to produce HFAMEs in very high yield (90%). A sequential chemical reduction and sulfation of the HFAMEs produced the sodium alkyl disulfates in high yields (>65%). SADM performs also 1.3-times better than dodecyl (1,3) disulfate, in surface tension tests. SADM shows also the formation of a specific critical micelle concentration (CMC) at a concentration 21-fold lower than SDS. The wettability of the SADM mixture is similar to SDS but the foaming volume of SADM is 1.5-fold higher. The foam is also more stable with its volume decreasing 3 times slower over time compared to SDS at their respective CMC values. Established sulfation technologies in chemical manufacturing could use the 3-hydroxy fatty acids methyl esters moiety (3-HFAME) given its origin from rapeseed oil and the extra OH residue on 3-position in the molecule, which affords the opportunity to produce disulfate surfactants with a proven superior performance to monosulphated surfactants. Thus, not only addressing environmental issues by avoiding threats of deforestation and monocultivation associated with palm oil use but also achieve a higher performance with lower use of surfactants.

Water-in-CO2 Microemulsions Stabilized by Fluorinated Cation-Anion Surfactant Pairs.

High-water-content water-in-supercritical CO2 (W/CO2) microemulsions are considered to be green, universal solvents, having both polar and nonpolar domains. Unfortunately, these systems generally require environmentally unacceptable stabilizers like long and/or multifluorocarbon-tail surfactants. Here, a series of catanionic surfactants having more environmentally friendly fluorinated C4-C6 tails have been studied in terms of interfacial properties, aggregation behavior, and solubilizing power in water and/or CO2. Surface tensions and critical micelle concentrations of these catanionic surfactants are, respectively, lowered by ∼9 mN/m and 100 times than those of the constituent single fluorocarbon-tail surfactants. Disklike micelles in water were observed above the respective critical micelle concentrations, implying the catanionic surfactants have a high critical packing parameter, which should be suitable for the formation of reverse micelles. Based on visual observation of phase behavior and Fourier transform infrared spectroscopic and small-angle neutron scattering studies, one of the three catanionic surfactants tested was found to form transparent single-phase W/CO2 microemulsions with a water-to-surfactant molar ratio of up to ∼50. This is the first successful demonstration of the formation of W/CO2 microemulsions by synergistic ion-pairing of anionic and cationic single-tail surfactants. This indicates that catanionic surfactants offer a promising approach to generate high-water-content W/CO2 microemulsions.

Aggregation Behavior of Medium Chain Fatty Acids Studied by Coarse-Grained Molecular Dynamics Simulation

Medium chain fatty acids (MCFA) are digestion products of lipid-rich food and lipid-based formulations, and they are used as transient permeability enhancers in formulation of poorly permeable compounds. These molecules may promote drug absorption by several different processes, including solubilization, increased membrane fluidity, and increased paracellular transport through opening of the tight junctions. Therefore, understanding the aggregation behavior of MCFAs is important. A number of studies have measured the critical micelle concentration (CMC) of MCFAs experimentally. However, CMC is highly dependent on system conditions like pH, temperature, and the ionic strength of the buffer used in different experimental techniques. In this study, we investigated the aggregation behavior of four different MCFAs using the coarse-grained molecular dynamics (CG-MD) simulations with the purpose to explore if CG-MD can be used to study MCFA interactions occurring in water. The ratio of deprotonated and non-charged MCFA molecules were manipulated to assess aggregation behavior under different pH conditions and within the box sizes of 22 × 22 × 44 nm3 and 44 nm3 for 1 μs. CMCs were calculated by performing CG-MD simulations with an increasing number of MCFAs. The resulting aggregate size distribution and number of free MCFA molecules were used to determine the CMC. The CMCs from simulations for C8, C10, and C12 were 1.8–3.5-fold lower than the respective CMCs determined experimentally by the Wilhelmy method. However, the variation of MCFA aggregate sizes and morphologies at different pH conditions is consistent with previous experimental observation. Overall, this study suggests that CG-MD is suitable for studying colloidal systems including various MCFAs.

On the investigation of acid and surfactant modification of natural clay for photocatalytic water remediation

In this study, a series of mineral and organic acids are introduced to natural clay modification. Several analytical techniques are employed to identify the physical and chemical changes in clay. The effect of surfactants on these properties is also investigated. The samples are prepared using simple acid treatment without filtration. The alteration in surface morphology is proportional to the acid strength as evident from SEM and XRD analyses. Therefore, the treatment with mineral acid and organic acid/HNO3 results in the formation of new layers by surface modification as depicted in SEM images, and a higher degree of suppression in characteristic XRD reflections of clay is noticed. However, the treatment with organic acids modifies the existing interlayer spacing of clay, and therefore, the XRD characteristic reflections of clay are less affected. These observations are also supported by FT-IR analysis. The surface area of modified clay is dependent on the acid strength, composition and size of counter-anion of acid. An increase in surface area and porosity is noticed after surfactant modification of HNO3-treated clay, where the change is more prominent at the concentration higher than their respective critical micelle concentration. Thermal stability is dependent on the chemical composition and surface area of clay materials. A relatively higher absorbance is observed for modified clay materials compared with untreated clay during DRS analysis. The catalytic efficiency of modified clay materials in Eriochrome Black T degradation has been demonstrated.

Enhanced oil recovery by nonionic surfactants considering micellization, surface, and foaming properties

Surfactants for enhanced oil recovery are important to study due to their special characteristics like foam generation, lowering interfacial tension between oleic and aqueous phases, and wettability alteration of reservoir rock surfaces. Foam is a good mobility control agent in enhanced oil recovery for improving the mobility ratio. In the present work, the foaming behavior of three nonionic ethoxylated surfactants, namely Tergitol 15-S-7, Tergitol 15-S-9, and Tergitol 15-S-12, was studied experimentally. Among the surfactants, Tergitol 15-S-12 shows the highest foamability. The effect of NaCl concentration and synthetic seawater on foaming behavior of the surfactants was investigated by the test-tube shaking method. The critical micelle concentrations of aqueous solutions of the different nonionic surfactants were measured at 300 K. It was found that the critical micelle concentrations of all surfactants also increased with increasing ethylene oxide number. Dynamic light scattering experiments were performed to investigate the micelle sizes of the surfactants at their respective critical micelle concentrations. Core flooding experiments were carried out in sand packs using the surfactant solutions. It was found that 22% additional oil was recovered in the case of all the surfactants over secondary water flooding. Tergitol 15-S-12 exhibited the maximum additional oil recovery which is more than 26% after water injection.

Spectrum of Membrane Morphological Responses to Antibacterial Fatty Acids and Related Surfactants.

Medium-chain saturated fatty acids and related compounds (e.g., monoglycerides) represent one class of membrane-active surfactants with antimicrobial properties. Most related studies have been in vitro evaluations of bacterial growth inhibition, and there is limited knowledge about how the compounds in this class destabilize lipid bilayers, which are the purported target within the bacterial cell membrane. Herein, the interaction between three representative compounds in this class and a supported lipid bilayer platform was investigated using quartz crystal microbalance-dissipation and fluorescence microscopy in order to examine membrane destabilization. The three tested compounds were lauric acid, sodium dodecyl sulfate, and glycerol monolaurate. For each compound, we discovered striking differences in the resulting morphological changes of supported lipid bilayers. The experimental trends indicate that the compounds have membrane-disruptive behavior against supported lipid bilayers principally above the respective critical micelle concentration values. The growth inhibition properties of the compounds against standard and methicillin-resistant Staphylococcus aureus bacterial strains were also tested. Taken together, the findings in this work improve our knowledge about how saturated fatty acids and related compounds destabilize lipid bilayers, offering insight into the corresponding molecular mechanisms that lead to membrane morphological responses.

Physicochemical Properties of Amphiphilic Drug and Anionic Surfactant Mixtures: Experimental and Theoretical Approach

Herein, we have reported the mixed micelle formation of amphiphilic phenothiazine drug promethazine hydrochloride (PMT) and anionic surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOT) mixtures at different compositions and temperatures (288.15, 293.15, 298.15, 303.15, and 308.15 K). A conductometric method is used to evaluate the critical micelle concentration (CMC) of binary mixtures. An attractive interaction between PMT and AOT mixed systems was indicated by the experimental and ideal critical micelle concentration (CMC and CMCid) values. The micellar mole fraction of anionic surfactant (, , , and ) was evaluated by different proposed models, and they prove the greater contribution of AOT in mixed micelle and increase with the increase in AOT concentration. Activity coefficients (f 1 and f 2) calculated by all recommended models were found to be always less than unity, signifying nonideality in the mixed systems. Different thermodynamic parameters have also been evaluated using the respective CMC values as a function of temperature. values were always found to be negative for all the systems; however, for pure drug as well as PMT–AOT mixed systems is negative at lower temperatures and positive at higher temperatures. The values are positive at all temperatures but their magnitude is higher at T = 303.15 K and above.

Towards smart polymeric drug carriers: self-assembling γ-substituted polycaprolactones with highly tunable thermoresponsive behavior.

Synthesis and ring opening polymerization of a new γ-substituted ε-caprolactone monomer, γ-(2-methoxyethoxy)-ε-caprolactone is reported. Amphiphilic diblock copolymers comprised of poly[γ-(2-methoxyethoxy)-ε-caprolactone] and thermosensitive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} as the hydrophobic and hydrophilic blocks, respectively, were prepared. The copolymers exhibited fully biodegradable backbones and highly tunable thermoresponsive behavior in the range of 31-43 °C. Additionally, the copolymers were shown to self-assemble in aqueous media above their respective critical micelle concentrations, on the order of 10-2 g L-1. Due to their thermosensitive, self-assembling, and biodegradable properties, these copolymers demonstrate potential for the use in polymeric micellar drug delivery systems.

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

Amyloid fibril formation is associated with a number of debilitating systemic and neurodegenerative diseases. One of the most prominent is Alzheimer disease in which aggregation and deposition of the Aβ peptide occur. Aβ is widely considered to mediate the extensive neuronal loss observed in this disease through the formation of soluble oligomeric species, with the final fibrillar end product of the aggregation process being relatively inert. Factors that influence the aggregation of these amyloid-forming proteins are therefore very important. We have screened a library of 96 amphipathic molecules for effects on Aβ(1-42) aggregation and self-association. We find, using thioflavin T fluorescence and electron microscopy assays, that 30 of the molecules inhibit the aggregation process, whereas 36 activate fibril formation. Several activators and inhibitors were subjected to further analysis using analytical ultracentrifugation and circular dichroism. Activators typically display a 1:10 peptide:detergent stoichiometry for maximal activation, whereas the inhibitors are effective at a 1:1 stoichiometry. Analytical ultracentrifugation and circular dichroism experiments show that activators promote a mixture of unfolded and β-sheet structures and rapidly form large aggregates, whereas inhibitors induce α-helical structures that form stable dimeric/trimeric oligomers. The results suggest that Aβ(1-42) contains at least one small molecule binding site, which modulates the secondary structure and aggregation processes. Further studies of the binding of these compounds to Aβ may provide insight for developing therapeutic strategies aimed at stabilizing Aβ in a favorable conformation.

Effect of pH, surface charge and counter-ions on the adsorption of sodium dodecyl sulfate to the sapphire/solution interface

The role of ionic interactions between sodium dodecyl sulfate, SDS, and sapphire surfaces have been studied using specular neutron reflection to determine the structure and composition of adsorbed surfactant layers. Increasing the pH of the solution from 3 to 9 reduces the adsorption by reversing the charge of the alumina. This occurs at lower pH for the R-plane (11¯02) than the C-plane (0001), corresponding to the different points of zero charge. The largest surface excess is about 6.5μmolm−2, the thickness of the adsorbed layer is about 24Å and it contains roughly 20% water. The hydrocarbon tails of the surfactant molecules clearly interpenetrate rather than form an ordered bilayer. The structure is similar in either pure water or in 0.1M NaCl when the surfactant is at the respective critical micelle concentration. Different structures were seen with lithium and cesium dodecyl sulfate. The CsDS forms dense layers with little or no hydration and a surface excess of about 10.5μmolm−2. The metal cation strongly influences the hydration of the adsorbed surfactant. An overall picture of ‘flattened micelles’ for the structure of the adsorbed layer is observed.