Influence of nonionic branched-chain alkyl glycosides on a model nano-emulsion for drug delivery systems.

The effect of incorporating new nonionic glycolipid surfactants on the properties of a model water/nonionic surfactant/oil nano-emulsion system was investigated using branched-chain alkyl glycosides: 2-hexyldecyl-ß(/α)-D-glucoside (2-HDG) and 2-hexyldecyl-ß(/α)-D-maltoside (2-HDM), whose structures are closely related to glycero-glycolipids. Both 2-HDG and 2-HDM have an identical hydrophobic chain (C16), but the former consists a monosaccharide glucose head group, in contrast to the latter which has a disaccharide maltose unit. Consequently, their hydrophilic-lipophilic balance (HLB) is different. The results obtained have shown that these branched-chain alkyl glycosides affect differently the stability of the nano-emulsions. Compared to the model nano-emulsion, the presence of 2-HDG reduces the oil droplet size, whereas 2-HDM modify the properties of the model nano-emulsion system in terms of its droplet size and storage time stability at high temperature. These nano-emulsions have been proven capable of encapsulating ketoprofen, showing a fast release of almost 100% in 24h. Thus, both synthetically prepared branched-chain alkyl glycosides with mono- and disaccharide sugar head groups are suitable as nano-emulsion stabilizing agents and as drug delivery systems in the future.

Electrostatic binding and hydrophobic collapse of peptide-nucleic acid aggregates quantified using force spectroscopy.

Knowledge of the mechanisms of interaction between self-aggregating peptides and nucleic acids or other polyanions is key to the understanding of many aggregation processes underlying several human diseases (e.g., Alzheimer's and Parkinson's diseases). Determining the affinity and kinetic steps of such interactions is challenging due to the competition between hydrophobic self-aggregating forces and electrostatic binding forces. Kahalalide F (KF) is an anticancer hydrophobic peptide that contains a single positive charge that confers strong aggregative properties with polyanions. This makes KF an ideal model to elucidate the mechanisms by which self-aggregation competes with binding to a strongly charged polyelectrolyte such as DNA. We use optical tweezers to apply mechanical forces to single DNA molecules and show that KF and DNA interact in a two-step kinetic process promoted by the electrostatic binding of DNA to the aggregate surface followed by the stabilization of the complex due to hydrophobic interactions. From the measured pulling curves we determine the spectrum of binding affinities, kinetic barriers, and lengths of DNA segments sequestered within the KF-DNA complex. We find there is a capture distance beyond which the complex collapses into compact aggregates stabilized by strong hydrophobic forces and discuss how the bending rigidity of the nucleic acid affects this process. We hypothesize that within an in vivo context, the enhanced electrostatic interaction of KF due to its aggregation might mediate the binding to other polyanions. The proposed methodology should be useful to quantitatively characterize other compounds or proteins in which the formation of aggregates is relevant.

Solvent-free model for self-assembling amphiphilic cyclodextrins. An off-lattice Monte Carlo approach in two dimensions.

By performing off-lattice Monte Carlo simulations in a two-dimensional space, we investigate the aggregation behavior of model Bouquet-shaped amphiphilic cyclodextrins. These molecules are able to self-assemble into a variety of supramolecular structures, such as micelles, vesicles, and long double-layered filaments. At high packing fractions, inverted micellar phases and lamellar liquid crystals have also been observed. Despite the number of approximations and restrictions imposed in our model, where the solution degrees of freedom are kept implicit and only the main physicochemical details are considered, we are able to reproduce the self-assembling behavior of amphiphilic cyclodextrins in its essential and most characteristic picture. The calculations of the cluster size distribution, density profiles, and radial distribution functions permit the characterization of the aggregates formed in the self-assembly process.

Physicochemical characterization of natural-like branched-chain glycosides toward formation of hexosomes and vesicles.

Synthetic branched-chain glycolipids have become of great interest in biomimicking research, since they provide a suitable alternative for natural glycolipids, which are difficult to extract from natural resources. Therefore, branched-chain glycolipids obtained by direct syntheses are of utmost interest. In this work, two new branched-chain glycolipids are presented, namely, 2-hexyldecyl ß(α)-D-glucoside (2-HDG) and 2-hexyldecyl ß(α)-D-maltoside (2-HDM) based on glucose and maltose, respectively. The self-assembly properties of these glycolipids have been studied, observing the phase behavior under thermotropic and lyotropic conditions. Due to their amphiphilic characteristics, 2-HDG and 2-HDM possess rich phase behavior in dry form and in aqueous dispersions. In the thermotropic study, 2-HDG formed a columnar hexagonal liquid crystalline phase, whereas in a binary aqueous system, 2-HDG formed an inverted hexagonal liquid crystalline phase in equilibrium with excess aqueous solution. Furthermore, aqueous dispersions of the hexagonal liquid crystal could be obtained, dispersions known as hexosomes. On the other hand, 2-HDM formed a lamellar liquid crystalline phase (smectic A) in thermotropic conditions, whereas multilamellar vesicles have been observed in equilibrium with aqueous media. Surprisingly, 2-HDM mixed with sodium dodecyl sulfate or aerosol OT induced the formation of more stable unilamellar vesicles. Thus, the branched-chain glycolipids 2-HDG and 2-HDM not only provided alternative nonionic surfactants with rich phase behavior and versatile nanostructures, but also could be used as new drug carrier systems in the future.

Impact of solvent physical parameters on the aggregation process of catanionic amphiphiles.

One of the most important solvent physical parameters for aggregation is the cohesive energy density (CED), for it gives an idea of the structured state of the solvent. Nevertheless, our studies on the behavior of catanionic amphiphiles in nonaqueous solvents demonstrated that in order to obtain objects the dielectric constant of the solvent was also a critical parameter, as a too high value of the dielectric constant caused the dissociation of the catanionic ion pair, leading to the separation of the two oppositely charged surfactants composing the catanionic amphiphiles, and then more likely to form small objects such as micelles rather than vesicles. In the case of our glucose-derived catanionic surfactants, vesicles could be obtained in pure water, in glycerol/water mixtures, and in water/formamide mixtures up to a certain ratio of formamide. Above a formamide volume fraction of 0.7, only micelles were formed.

Organogels from a vitamin C-based surfactant.

A new double chained surfactant, 2-octyl-dodecanoyl-6-O-ascorbic acid (8ASC10), with a L-ascorbic acid unit as the polar headgroup was synthesized for the first time. The behavior of the compound in the dry solid state has been characterized through DSC, XRD, and SAXS measurements. The surfactant forms stable viscous organogels in the presence of suitable organic solvents and also water-induced organogels upon addition of water to the organogel. These mixtures show shear-thinning properties and are birefringent. The behavior and properties of the organogels have been studied through rheology, DSC, and SAXS experiments. The organogels possess the same antioxidant properties of the original L-ascorbic acid ring and can be used to solubilize and protect valuable organic molecules.