Characterization of VitE-TPGS Micelles Linked to Poorly Soluble Pharmaceutical Compounds Exploiting Pair Distribution Function’s Moments

<b>Background:</b> Micelles have attracted significant interest in nanomedicine as drug delivery systems. This study investigates the morphology of micelles formed by the D-α-tocopherol polyethylene glycol 1000 succinate (VitE-TPGS) surfactant in the presence and absence of, respectively, a poorly soluble pharmaceutical compound (PSC), i.e., Eltrombopag (0.08 wt%) and CaCl₂ (0.03 wt%). The aim was to assess the micelles' ability to solubilize the PSC and potentially shield it from Ca²⁺ ions, simulating in vivo conditions. <b>Methods:</b> For this purpose, we have developed a novel theoretical approach for analyzing Pair Distribution Function (PDF) data derived from Small-Angle X-ray Scattering (SAXS) measurements, based on the use of PDF's moments. <b>Results:</b> Our spheroid-based model was able to characterize successfully the micellar morphology and their interactions with PSC and CaCl₂, providing detailed insights into their size, shape, and electron density contrasts. The presence of PSC significantly affected the shape and integral of the PDF curves, indicating incorporation into the micelles. This also resulted in a decrease in the micelle size, regardless of the presence of CaCl₂. When this salt was added, it reduced the amount of PSC within the micelles. This is likely due to a decrease in the overall PSC availability in solution, induced by Ca²⁺ ions. <b>Conclusions:</b> This advanced yet straightforward analytical model represents a powerful tool for characterizing and optimizing micelle-based drug delivery systems.