Xia Dengning, Yu Hongzhen, Tao Jinsong, Zeng Jianrong, Zhu Quanlei, Zhu Chunliu, Gan Yong
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China; Department of Pharmacy, Medical College of Nanchang University, Nanchang 330066, China.
Colloids Surf B Biointerfaces. 2016 May 1;141:301-310. doi: 10.1016/j.colsurfb.2016.01.047. Epub 2016 Jan 29.
Our previous study demonstrated that the retention of drug in the hydrophobic core of Soluplus micelle greatly impeded drug absorption from gastrointestinal tract. Using supersaturated polymeric micelles can improve drug release, however, insufficient maintaining of supersaturation of drug is still unfavorable for drug absorption. Here, we report adding small amount of small molecule, sodium dodecyl sulfate (SDS), to Soluplus solution can form a Soluplus-SDS complex. This complex not only showed a higher solubilization capability for the model drug cyclosporine A (CsA), but also maintained a longer period of and higher supersaturation than was achieved with Soluplus alone. The Soluplus-SDS interactions were characterized by analyzing surface tension, small-angle X-ray scattering (SAXS), fluorescence spectra, and nuclear magnetic resonance spectroscopy. The results demonstrated that the formation of Soluplus-SDS complex via SDS adsorption on hydrophobic segments of Soluplus, which have more hydrophobic domain than that of Soluplus micelle, contributed significantly to the solubilization and stabilization of supersaturated CsA. Using this amphiphilic copolymer-small molecule surfactant system, the cellular uptake and rat in vivo absorption of CsA were more effectively achieved than pure Soluplus. The area under the plasma concentration-time curve (AUC) and the maximal plasma concentration (Cmax) achieved by CsA-loaded Soluplus-SDS complex were 1.58- and 1.8-times higher than the corresponding values for CsA-loaded pure Soluplus, respectively. This study highlighted the benefits of Soluplus-SDS complex for optimizing the solubilization and oral absorption of a drug with low aqueous solubility.
我们之前的研究表明，药物保留在Soluplus胶束的疏水核心中会极大地阻碍药物从胃肠道的吸收。使用过饱和聚合物胶束可以改善药物释放，然而，药物过饱和度的维持不足仍然不利于药物吸收。在此，我们报道向Soluplus溶液中添加少量小分子十二烷基硫酸钠（SDS）可形成Soluplus-SDS复合物。该复合物不仅对模型药物环孢素A（CsA）表现出更高的增溶能力，而且与单独使用Soluplus相比，能维持更长时间的更高过饱和度。通过分析表面张力、小角X射线散射（SAXS）、荧光光谱和核磁共振光谱对Soluplus-SDS相互作用进行了表征。结果表明，Soluplus-SDS复合物的形成是通过SDS吸附在Soluplus的疏水链段上，其疏水结构域比Soluplus胶束更多，这对过饱和CsA的增溶和稳定有显著贡献。使用这种两亲共聚物-小分子表面活性剂体系，CsA的细胞摄取和大鼠体内吸收比纯Soluplus更有效。负载CsA的Soluplus-SDS复合物实现的血浆浓度-时间曲线下面积（AUC）和最大血浆浓度（Cmax）分别比负载CsA的纯Soluplus的相应值高1.58倍和1.8倍。这项研究突出了Soluplus-SDS复合物在优化低水溶性药物的增溶和口服吸收方面的优势。
