A new kind of catanionic assembly was developed that associates a sugar-based surfactant with a non-steroidal anti-inflammatory drug (NSAID). Three different assemblies using indomethacin, ibuprofen and ketoprofen as NSAIDs were easily obtained in water by an acid-base reaction. These assemblies formed new amphiphilic entities because of electrostatic and hydrophobic effects in water and led to the spontaneous formation of vesicles. These catanionic vesicles were then tested as potential NSAID delivery systems for dermatological application. The anti-inflammatory activity was evaluated in vivo, and this study clearly showed an improved therapeutic effect for NSAIDs that were formulated as catanionic vesicles. These vesicles ensured a slower diffusion of the NSAID through the skin. This release probably increased the time of retention of the NSAID in the targeted strata of the skin. Thus, the present study suggests that this catanionic bioactive formulation could be a promising dermal delivery system for NSAIDs in the course of skin inflammation treatment.

Bolaamphiphilic molecules containing a hydrophobic skeleton and two hydrophilic head groups at both ends [1] receive particular interest since the early 1980s, as synthetic bolaamphiphiles [2] are able to form monolayered membranes. [3,4] Moreover, ultrasonication of aqueous dispersions of bolaamphiphile monolayers gives rise to spherical particles made of monolayer lipid membranes. [5][6][7] These aggregates are attractive candidates for transporting active substances inside their hydrophilic core. With this regard, sugar-derived bolaamphiphiles have been synthesized by different research groups [8][9][10][11][12] to enhance, for example, their affinity to target cells. Although bolaamphiphiles are able to form vesicles, the energy used to induce the nonspontaneous curvature is a limitation to further industrial applications. To avoid this constraint, the bolaamphiphiles can be associated with an oppositely charged surfactant [13][14][15] to prepare catanionic mixtures, which are known to spontaneously form thermodynamically stable vesicles. [16,17] The aim of this work is the controlled design of new triblock catanionic amphiphiles that spontaneously form stable vesicles. A sugar-based bolaamphiphile, bearing a central amine function associated with carboxylic fatty diacids, was prepared and the chain length of the diacid was varied in order to correlate the aggregation behavior of these mixtures with the most favorable arrangement evaluated by molecular modelling.The synthesis of a bolaamphiphile derived from a sugar has been performed using an amidation reaction in methanol between bis(6-aminohexyl)amine and d-(+)-1,5-gluconolactone (Scheme 1). The mechanism is a nucleophilic addition reaction which takes place only at the primary amine group. Even if the secondary nitrogen atom is more nucleophilic than the primary one, no further reaction of the bolaform amphiphile was observed, prevented probably by steric hindrance. Also, the use of methanol as solvent favored, compared with the acid form, the lactone form and therefore increased the yield of the reaction (Scheme 1).Catanionic associations of oppositely charged surfactants usually undergo spontaneously curvature of the bilayer. This feature of catanionic surfactants could be extended to catanionic bolaamphiphiles forming monolayer vesicles. The completion of the acid-base reaction between two equivalents of the aminosugar 1 and one equivalent of the corresponding alkanedioic acid (Scheme 2) was enabled by the hydrophobic effect of the alkyl chains in water. [18] Proton transfer between the carboxylic acid and the amine produces a catanionic pair, characterized by Fourier transform infrared (FT-IR) spectroscopy. [19] Indeed, FT-IR characterization of association 4 showed complete disappearance of the carboxylic acid absorption band at 1 694 cm À1 and appearance of the carboxylate stretching symmetric and asymmetric bands at 1 405 and 1 578 cm À1. In addition, typical NH 2 + stretching absorption bands at 2 492 and 2 123 cm À1 for association 2 also confirm...

An original catanionic assembly based on a sugar‐derived surfactant and a non‐steroidal anti‐inflammatory drug (NSAID) is described by I. Rico‐Lattes et al. in their Full Paper on page 3039 ff. These catanionic vesicles provided a bioactive formulation for the dermal administration of NSAIDs. This original formulation showed very interesting benefits. It improved the anti‐inflammatory activity of the NSAID in vivo and it ensured a slower diffusion of the NSAID through the skin.