Isothermal Titration Calorimetry Directly Measures the Selective Swelling of Block Copolymer Vesicles in the Presence of Organic Acid

[Image: see text] Block copolymer (BCP) vesicles loaded with drug molecules may have a nonidentical swelling behavior due to the strong interactions between BCP vesicles and loaded molecules. A thermodynamic study of the swelling for such a system is of great importance in clarifying their pH-gated drug delivery behavior. In this study, the selective swelling of polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) vesicles in the presence of different acids was compared using dynamic light scattering, zeta-potential, and isothermal titration calorimetry (ITC) measurements. Transmission electron microscopy observation verified that these PS-b-P2VP vesicles were mainly multilamellar. Importantly, using the ITC measurement, we first compared the thermodynamic parameters, including ΔH, ΔG, and ΔS, association binding sites (N), and binding association constants (K(a)) in the selective swelling of the PS-b-P2VP vesicles in low pH (pH ∼3.5), with or without a hydrogen bonding interaction. We observed that the existence of a hydrogen bonding interaction between tartaric acid/malic acid and PS-b-P2VP generates a limitation to the selective swelling of PS-b-P2VP vesicles, in which conditions will depend on the molecular structures of the organic acids and PS-b-P2VP. This work first provides a quantitative insight on the swelling of BCP vesicles in the presence of hydrogen bonding and highlights the power of ITC measurements for investigating the structural transformation of polymer nanostructures.