Department of Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
Department of Kampo Pharmacy, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
Molecules. 2024 Oct 19;29(20):4945. doi: 10.3390/molecules29204945.
The solubilization behavior of medroxyprogesterone (MP) within gemini surfactant micelles (14-6-14,2Br) was investigated and compared with that of progesterone to uncover distinct solubilization mechanisms. We employed H-NMR and 2D ROESY spectroscopy to elucidate the spatial positioning of MP within the micelle, revealing that MP integrates more deeply into the micellar core. This behavior is linked to the unique structural features of MP, particularly its 17β-acetyl group, which promotes enhanced interactions with the hydrophobic regions of the micelle, while the 6α-methyl group interacts with the hydrophilic regions of the micelle. The 2D ROESY correlations specifically highlighted interactions between the hydrophobic chains of the surfactant and two protons of MP, H22 and H19. Complementary machine learning and electron density analyses supported these spectroscopic findings, underscoring the pivotal role of the molecular characteristics of MP in its solubilization behavior. These insights into the solubilization dynamics of MP not only advance our understanding of hydrophobic compound incorporation in gemini surfactant micelles but also indicate the potential of 14-6-14,2Br micelles for diverse drug delivery applications.
我们研究了孕二烯酮（MP）在双子表面活性剂胶束（14-6-14,2Br）中的增溶行为，并将其与孕酮进行了比较，以揭示不同的增溶机制。我们采用 H-NMR 和 2D ROESY 光谱学来阐明 MP 在胶束中的空间定位，结果表明 MP 更深入地整合到胶束的核心中。这种行为与 MP 的独特结构特征有关，特别是其 17β-乙酰基，促进了与胶束疏水区的增强相互作用，而 6α-甲基则与胶束的亲水区相互作用。2D ROESY 相关特别突出了表面活性剂疏水链与 MP 的两个质子，H22 和 H19 之间的相互作用。补充的机器学习和电子密度分析支持了这些光谱学发现，强调了 MP 的分子特征在其增溶行为中的关键作用。这些对 MP 增溶动力学的深入了解不仅增进了我们对双子表面活性剂胶束中疏水性化合物掺入的理解，还表明了 14-6-14,2Br 胶束在各种药物输送应用中的潜力。
