Nanotechnology Research Center, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Golestan Ave, Ahvaz 67123, Iran.
Molecules. 2018 Jul 31;23(8):1904. doi: 10.3390/molecules23081904.
The low oral bioavailability of ciprofloxacin is associated with two distinct challenges: its low aqueous solubility and efflux by p-glycoproteins (P-gp) in the intestinal membrane. Several studies were conducted in order to improve its solubility and permeability through the gastrointestinal membrane. In this study, in a full factorial design study, eight polymeric micelles were prepared and their characteristics, including particle size, loading and release rate were evaluated. Polymeric micelles demonstrated particle sizes below 190 nm and 27⁻88% loading efficiency. Drug release was affected by drug solubility, polymeric micelle erosion and swelling in simulated gastrointestinal fluids. An optimized polymeric micelle was prepared based on appropriate characteristics such as high drug loading and low particle size; and was used for a permeation study on Caco-2 cells. Optimized polymeric micelles with and without ginsenoside and ginsenoside alone enhanced drug permeability through Caco-2 cells significantly in the absorptive direction. The effect of ginsenoside was dose dependent and the maximum effect was seen in 0.23 mg/mL concentration. Results showed that P-gp may not be responsible for ciprofloxacin secretion into the gut. The main mechanism of ciprofloxacin transport through Caco-2 cells in both directions is active diffusion and P-gp has inhibitory effects on ciprofloxacin permeability in the absorptive direction that was blocked by ginsenoside and micelles without ginsenoside.
其在水中的溶解度低，以及在肠膜中被 P-糖蛋白（P-gp）外排。为了提高其在胃肠道膜中的溶解度和通透性，已经进行了多项研究。在这项研究中，采用完全因子设计研究方法制备了 8 种聚合物胶束，并对其特性（包括粒径、载药量和释放率）进行了评估。聚合物胶束的粒径均低于 190nm，载药量为 27-88%。药物释放受到药物溶解度、聚合物胶束在模拟胃肠道液体中的侵蚀和溶胀的影响。基于适当的特性（如高载药量和低粒径），制备了一种优化的聚合物胶束，并用于 Caco-2 细胞的渗透研究。载有和未载人参皂苷以及单独人参皂苷的优化聚合物胶束显著增强了药物在吸收方向上通过 Caco-2 细胞的渗透性。人参皂苷的作用具有剂量依赖性，在 0.23mg/mL 浓度下达到最大效果。结果表明，P-gp 可能不是将环丙沙星分泌到肠道中的原因。环丙沙星在两个方向上通过 Caco-2 细胞的主要传输机制是主动扩散，P-gp 对吸收方向中环丙沙星的通透性具有抑制作用，而人参皂苷和无人参皂苷的胶束则可以阻断这种抑制作用。
