Unveiling the Aggregation Behavior of Doxorubicin Hydrochloride in Aqueous Solution of 1-Octyl-3-methylimidazolium Chloride and the Effect of Bile Salt on These Aggregates: A Microscopic Study

Abstract

In this article, we have unveiled the aggregation behavior of a potent chemotherapeutic drug, doxorubicin hydrochloride (Dox) in a well-known imidazolium based surface active ionic liquid (SAIL), 1-octyl-3-methylimidazolium chloride (C₈mimCl). The aggregates formed by Dox in C₈mimCl have been characterized using dynamic light scattering (DLS), fluorescence lifetime imaging microscopy (FLIM), high-resolution transmission electron microscopy (HR-TEM), analytical transmission electron microscopy (analytical TEM), field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), and Fourier-transform infrared spectroscopy (FTIR) measurements. It is found that Dox forms large spherical aggregates in the presence of C₈mimCl SAIL. We have also explored the driving force behind this aggregation behavior of Dox in C₈mimCl. Furthermore, it is observed that in the presence of a common bile salt, sodium cholate (NaCh), Dox/C₈mimCl spherical aggregates disrupt to form rodlike fibrillar aggregates. Therefore, formation of spherical aggregates and also its disruption into rodlike fibrillar aggregates have been performed, and this is expected to open a new scope for the design of a new generation smart drug delivery system where the drug itself aggregates to form the delivery system.