The soluble state of amphiphile and crosslinked derivatives of carboxymethylpullulan was investigated by physicochemical analyses. This soluble state also called infinite sol was obtained from hydrogels after a short-time temperature treatment. The analyses show a large distribution in size for the species in solution (from some nanometers to some micrometers). Furthermore, they also reveal the presence of hydrophobic associations (intra and/or intermolecular) in addition to the chemical links. The nature of these hydrophobic interactions will depend on the polymer concentration and on the solvent used.KEY WORDS: Polysaccharide / Crosslinking / Hydrogels / Amphiphile / Self-organization / Hydrogels are suitable materials for drug delivery applications in biomedical and pharmaceutical fields. Indeed, active compounds can be easily entrapped and released, specially by responsive-stimuli devices which undergo phase transition or swelling-deswelling behaviour in response to environmental changes (temperature, pH, ionic strength, . . .). 1-3 Furthermore, they resemble natural living tissues by their ability to absorb and retain huge quantity of fluids and by their consistency, giving them a good biocompatibility. 4 Since several years, numerous studies have been interested in hydrogels based on polysaccharides and their derivatives because of their advantages over synthetic polymers. In fact, they are abundant, largely water soluble, biocompatible and descendent from renewable sources. 5 More recently, attention is focused on the development of amphiphilic networks able to transport amphiphilic and hydrophobic drugs. 6,7 Two majority ways are used to elaborate amphiphilic hydrogels based on polysaccharides. The most widespread way consists in grafting on the polymer backbone hydrophobic chains which self-aggregate in solution so creating cross-linking points but also hydrophobic domains. The most famous examples of this kind of systems are derivatives of pullulan bearing cholesteryl groups (CHP) which provide by self-aggregation particles able to complex hydrophobic molecules and proteins. [8][9][10][11][12][13] An other example consists of carboxymethylpullulan grafting by alkyl pendant groups. 14 The second technique consists in a chemical cross-linking with a hydrophobic agent. Few studies have been interested in this way although it gives in one step cross-links and amphiphilic character. So, Dulong et al. have elaborated amphiphilic carboxymethylpullulan networks using adipic dihydrazide 15 and N-hydroxysuccinimide, 16 whereas Coviello and Matricardi have choosen dibromohexan as cross-linking agent to obtain hydrogels from scleroglucan 17 and polygalacturonic acid. 18 We use the second method and dibromohexan to elaborate amphiphilic systems based on carboxymethylpullulan, an anionic derivative of pullulan (Figure 1). In a recent paper, 19 we showed that the cross-linking reaction was very fast, leading to creation of high crosslink density clusters as described by Hoffman. 20 On the other hand, we demonstrated ...