Abstract：
Candesartan cilexetil (CAN) is administered for treating hypertension and heart failure. CAN suffers poor oral bioavailability, owing to limited aqueous solubility, and first-pass metabolism. Solusomes (novel Soluplus® enriched nano-vesicular carriers) combine the merits of Soluplus®, and the traditional liposomes. They were explored to increase CAN solubility, allow a high drug release rate, and improve the oral drug bioavailability. Solusomes were developed via thin film hydration technique utilizing lipid (phosphatidylcholine; PC) and polymeric solubilizer (Soluplus®; Solu). S6 system comprising PC (0.1% w/v), CAN and Soluplus® (at 1:5 ratio; w/w), following a 5 min sonication period, was the optimum one with respect to drug entrapment efficiency (83.5 ± 2.6%), drug loading (11.9 ± 0.3%), particle size and shape (377.2 ± 12.1 nm, spherical), zeta-potential (-19.6 ± 2.1 mV), saturated drug solubility (32.09 ± 0.71 µg/mL), drug released % after 1 h (68 ± 0.9%), and stability. Significantly higher Cmax (969.12 ± 46.3 ng/mL), shorter median Tmax (1h), and improved relative bioavailability (≈ 6.8 folds) in rabbits could evidence the potential of S6 system in enhancing oral CAN bioavailability. S6 solusomes act as dual platform to improve the oral drug bioavailability and maintain effective drug concentration for a prolonged period.
摘要：
坎地沙坦西酯（CAN）用于治疗高血压和心力衰竭。CAN口服生物利用度差，由于有限的水溶性，和首过代谢。Solusomes（新型Soluplus®富集纳米囊泡载体）结合了Soluplus®的优点，和传统的脂质体。他们被探索增加CAN溶解度，允许高药物释放率，提高口服药物的生物利用度。通过薄膜水合技术利用脂质(磷脂酰胆碱;PC)和聚合物增溶剂(Soluplus®;Solu)开发了Solusomes。S6系统包括PC（0.1%w/v），CAN和Soluplus®(比例为1:5；w/w)，超声处理5分钟后，在药物包封率方面是最佳的(83.5±2.6%)，载药量（11.9±0.3%），颗粒尺寸和形状(377.2±12.1nm，球形)，zeta电位（-19.6±2.1mV），饱和药物溶解度（32.09±0.71µg/mL），1小时后药物释放%（68±0.9%），和稳定性。Cmax显著升高(969.12±46.3ng/mL),较短的中位数Tmax（1h），兔体内相对生物利用度的提高（≈6.8倍）可以证明S6系统在提高口服CAN生物利用度方面的潜力。S6solusomes作为双平台，以提高口服药物的生物利用度，并维持有效的药物浓度长时期。
