De Caro Liberato, Stoll Thibaud, Grandeury Arnaud, Gozzo Fabia, Giannini Cinzia
Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Via Amendola 122/O, 70125 Bari, Italy.
Excelsus Structural Solutions (Swiss) AG, Park Innovaare, Parkstrasse 1, 5234 Villigen, Switzerland.
Pharmaceutics. 2025 Mar 27;17(4):431. doi: 10.3390/pharmaceutics17040431.
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 CaCl (0.03 wt%). The aim was to assess the micelles' ability to solubilize the PSC and potentially shield it from Ca ions, simulating in vivo conditions. 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. Our spheroid-based model was able to characterize successfully the micellar morphology and their interactions with PSC and CaCl, 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 CaCl. 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 Ca ions. This advanced yet straightforward analytical model represents a powerful tool for characterizing and optimizing micelle-based drug delivery systems.
胶束作为药物递送系统在纳米医学领域引起了广泛关注。本研究分别在存在和不存在难溶性药物化合物（PSC）的情况下，研究了由琥珀酸聚乙二醇1000维生素E（VitE - TPGS）表面活性剂形成的胶束的形态，其中难溶性药物化合物分别为艾曲泊帕（0.08 wt%）和氯化钙（0.03 wt%）。目的是评估胶束溶解PSC并可能使其免受钙离子影响的能力，以模拟体内条件。为此，我们基于对PDF矩的使用，开发了一种新颖的理论方法来分析从小角X射线散射（SAXS）测量中获得的对分布函数（PDF）数据。我们基于球体的模型能够成功地表征胶束形态及其与PSC和氯化钙的相互作用，从而深入了解它们的大小、形状和电子密度对比。PSC的存在显著影响了PDF曲线的形状和积分，表明其被纳入胶束中。这也导致了胶束尺寸的减小，无论氯化钙是否存在。当加入这种盐时，它减少了胶束内PSC的量。这可能是由于钙离子导致溶液中PSC的总体可用性降低。这种先进而直接的分析模型是表征和优化基于胶束的药物递送系统的有力工具。
