Department of Drug Development and UNIDDS, School of Medicine, Inha University, 8F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712, South Korea.
Int J Pharm. 2013 Jan 30;441(1-2):757-64. doi: 10.1016/j.ijpharm.2012.10.018. Epub 2012 Oct 23.
Self-microemulsifying drug delivery system (SEDDS) cored-polymeric nanocapsules (NC) were fabricated using emulsion diffusion method for the controlled oral absorption of the poorly water soluble drug, cyclosporine. Poly-dl-lactide (PDLLA) was used as the shell-forming polymer. The NCs in different polymer/oil ratios (from 25/125 to 125/125) were prepared following a solvent-diffusion method. Especially, the SEDDS oil-core compositions, which can form microemulsions on dispersion, were selected based on a pseudo-phase diagram study and further optimized based on the solubility and permeability studies. The prepared NCs were with a mean diameter of 150-220 nm and 9.4-4.5% w/w drug loading. In vivo study in rats showed that the optimized NC(50/125) and NC(100/125) released the drug in controlled way as well as enhanced the bioavailability significantly with AUC(0-24h) values of 14880.3±1470.6 and 12657.8±754.5 ng h/ml, respectively, compared to that of SEDDS-core solution (9878.9±409.6 ng h/ml). Moreover it was observed that the NCs maintained blood concentration of cyclosporine (>500 ng/ml) for 14-20 h but in the case of control formulation it was only 7.33 h. Our results suggest that the prepared NCs could be a potential carrier for the oral controlled release formulation of cyclosporine.
自微乳药物传递系统（SEDDS）核-聚合物纳米胶囊（NC）采用乳液扩散法制备，用于控制环孢素的口服吸收。聚-dl-丙交酯（PDLLA）用作壳形成聚合物。采用溶剂扩散法制备不同聚合物/油比（从 25/125 到 125/125）的 NC。特别是，SEDDS 油芯组合物可以在分散时形成微乳液，根据伪相图研究进行选择，并根据溶解度和渗透性研究进一步优化。所制备的 NC 的平均直径为 150-220nm，载药量为 9.4-4.5%w/w。在大鼠体内研究表明，优化的 NC（50/125）和 NC（100/125）以控制方式释放药物，并显著提高生物利用度，AUC（0-24h）值分别为 14880.3±1470.6 和 12657.8±754.5ng h/ml，与 SEDDS 核溶液（9878.9±409.6ng h/ml）相比。此外，观察到 NC 使环孢素的血液浓度（>500ng/ml）维持 14-20h，而在对照制剂中仅为 7.33h。我们的结果表明，所制备的 NC 可作为环孢素口服控释制剂的潜在载体。
