Drug-induced transitions from micelles to vesicles in ionic surfactant solutions

Surfactant solutions play key roles in scientific research and technological applications. Here we investigated solutions that combined an ionic surfactant, Cetylpyridinium Chloride (CPyCl), with a non-steroidal, anti-inflammatory drug, Sodium Diclofenac (Diclo). The study covered a wide range of compositions and utilized both rheology and cryogenic-Electron Microscopy (cryo-EM). The solutions were prepared at three different concentrations of CPyCl: 5.0 mM, 16.7 mM and 33.0 mM, and we maintained the ratio of surfactant to salt, R=CPyCl/Diclo, within the range of 0.24<1.2. Linear viscoelasticity was measured at 25°C. The use of dilute solutions allowed for detailed cryo-EM imaging. By tracking the evolution of the zero-frequency viscosity as a function of Diclo concentration, we identified distinct regions of different rheological responses. The correlation between frequency sweep data and cryo-EM images enabled us to link these regions to specific morphological transitions ranging from spherical micelles to long and entangled wormlike micelles, to branched networks and, eventually, to perforated vesicles. For some systems, we were able to measure the complete spectrum of relaxation times, including the shortest characteristic Rouse time at high frequencies, previously only achieved by Diffusive Wave Spectroscopy. The use of existing models to evaluate the relevant important microstructural parameters such as entanglement, contour, and persistence lengths allowed us to establish a clear correlation between the microstructural parameters derived through rheology and the insights from the cryo-EM analysis.