Unraveling the solubilization and cytotoxicity study of poorly water-soluble anti-inflammatory drug in aqueous Gemini surfactants solution with physicochemical characterization and simulation study

Abstract This work investigates the use of quaternary ammonium based Gemini surfactants (GS) to examine the solubilization and stabilization of a poorly water soluble anti-inflammatory drug Diclofenac (Df). Here we demonstrate the effect of pH on the suspension profile of Df release where it exhibits maximum solubility and absorbance at pH = 10. Interaction process of such cationic GS with Df have been systematically characterized using tensiometry and UV–vis spectroscopy techniques from pre-micellar to post-micellar regions. The spectral results revealed that all the individual GS bind on Df electrostatically resulting in GS + Df complexation. For all the three GS examined, the critical micelle concentration (CMC) was found to decrease in presence of Df following the order: 12- 2 -12 > 12- 2 -16 > 16- 2 -16 which inferred that 12- 2 -12 can effectively suppress Df degradation at very low concentration. In comparison to 12- 2 -12, 12- 2 -16 and 16- 2 -16 exhibited weaker interaction with Df which limits the stability/solubility of Df in their respective micelles. The aggregation behavior of Df with various GS was investigated by dynamic light scattering (DLS) method. The structural orientation of GS and Df was elucidated by molecular simulation study using Gauss View 5.0.9. The influence of the 12- 2 -12 in presence of Df on the cervical cell morphology has been undertaken to understand the cytotoxic effect using MTT assay.