Phase Behavior of Vesicle-Forming Block Copolymers in Aqueous Solutions Jo¨rg Braun, Nico Bruns, Thomas Pfohl, Wolfgang Meier* Introduction Amphiphilic block copolymers are macromolecules con- sisting of a hydrophilic segment covalently attached to a hydrophobic segment. They are unique and versatile building blocks in supramolecular polymer chemistry, both for the generation of highly organized, self-assembled structures and for the structural control of material interfaces. [1] In the absence of solvents, the phase-behavior of block-copolymers can be described in terms of the strength of the interactions between the blocks (x), the total number of statistical segments (N), the volume fraction of one of the blocks ( f), and the differences in the conforma- tional properties of the polymer chains (e). [2] In dilute aqueous solutions, however, block copolymers self-assem- ble into nanoscopic structures. This self-assembly process cannot be described solely by the above-mentioned parameters. In aqueous solution, the hydrophobic effect also plays an important role in determining the thermo- dynamically preferred structure. [3] The effect in turn depends on the polymer concentration, the volume ratio of the two different segments, and the chemical structure of the hydrophilic and hydrophobic blocks. Self-assembled structures of block-copolymers in solution are micelles, rods, and vesicles, among others. [4] The latter morphology is of greatest interest because polymeric vesicles are more stable than lipid-based vesicles [5] and can also be used to encapsulate guest molecules, e.g. drugs. Thus, they can be used as drug delivery devices. [6] Further applications of polymer vesicles are as nanoreactors, as supramolecular biomaterials, in cosmetics, in food formulations, as lab-on- a-chip components, and as building blocks in microfluidic and bioprocessing applications. [7] Commercial formula- tions are often made by simply dissolving dry amphiphilic polymers in water. A simplistic view is that amphiphiles spontaneous self-assemble into vesicles, but the molecular processes involved in vesicle formation are much more complex. Water diffuses into the bulk polymer, swells hydrophilic domains, and eventually swollen lamella sheets start to unbind, that finally bend and close to form vesicles. Thus, the polymer traverses the whole Full Paper J. Braun, N. Bruns, T. Pfohl, W. Meier Department of Chemistry, University of Basel, Klingelberstrasse 80, CH-4056 Basel, Switzerland E-mail: wolfgang.meier@unibas.ch The binary phase diagram of amphiphilic poly(ethylene oxide)-block-poly(g -methyl-e-capro- lactone) block copolymers in water is examined for four polymers having the same hydrophilic block length but different hydrophobic block lengths across the whole concentration range. The bulk polymers show no ordered morphology. With increasing water concen- tration the polymers undergo transitions from lamellar phases to packed vesicles and sub- sequently all polymers self-assemble into vesicles in dilute aqueous solutions. Addition- ally, the largest polymer forms an inverse hexagonal phase, and the smallest polymer self-aggregates into rod-like micelles and showed a hexagonal phase. Macromol. Chem. Phys. 2011, 212, 1245–1254 ß 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com DOI: 10.1002/macp.201100012 1245