In this work, we present a new method to nanodisperse the pH-sensitive antibiotics oxolinic acid and flumequine by the use of a pH-sensitive synthetic polyketone derivative with amphiphilic characteristics. The pH-sensitive polymer bears imidazolium residues on pendant groups as weak acids, and its solvophobic properties can be tuned by changing the pH. While the antibiotics are soluble in water at pHs higher than 7.0 for flumequine and 8.4 for oxolinic acid, and the polymer is soluble in water at pHs lower than 5.5, nanoprecipitates presenting hydrodynamic radius of 35–100 nm and positive zeta potential containing both the polymer and any of the antibiotics are formed at pH 6.8 by mixing stock solutions whose pH has been adjusted to 5.4 for the polymer and higher than 10 for the antibiotics. The out-of-equilibrium process occurring upon mixing both solutions produces pH changing, molecular arrangement, and a controlled collapse of the system in the form of nano- and submicron particles. The driving forces for the arrangements are found among hydrophobic forces, long-range electrostatic interactions, and short range aromatic–aromatic interactions. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42363.