Ionic liquids (ILs) have increasingly been studied as key materials to upgrade the performance of many pharmaceutical formulations. In controlled delivery systems, ILs have improved multiple physicochemical properties, showing the relevance of continuing to study their incorporation into these formulations. Transfersomes are biocompatible nanovesicular systems, quite useful in controlled delivery. They have promising characteristics, such as elasticity and deformability, making them suitable for cutaneous delivery. Nonetheless, their overall properties and performance may still be improved. Herein, new TransfersomILs systems to load rutin were developed and the physicochemical properties of the formulations were assessed. These systems were prepared based on an optimized formulation obtained from a Box-Behnken factorial design (BBD). The impact of imidazole-based ILs, cholinium-based ILs, and their combinations on the cell viability of HaCaT cells and on the solubility of rutin was initially assessed. The newly developed TransfersomILs containing rutin presented a smaller size and, in general, a higher association efficiency, loading capacity, and total amount of drug release compared to the formulation without IL. The ILs also promoted the colloidal stability of the vesicles, upgrading storage stability. Thus, ILs were a bridge to develop new TransfersomILs systems with an overall improved performance.
Keywords: Box–Behnken factorial design; TransfersomILs; cutaneous delivery; ionic liquids; nanosystems; rutin.