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

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 Δ H , Δ G , and Δ S , 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.