Ali Md Ashraf, Kataoka Noriko, Ranneh Abdul-Hackam, Iwao Yasunori, Noguchi Shuji, Oka Toshihiko, Itai Shigeru
Department of Pharmaceutical Engineering & Drug Delivery Science, Graduate School of Integrated Pharmaceutical & Nutritional Sciences, University of Shizuoka.
Chem Pharm Bull (Tokyo). 2017;65(1):42-48. doi: 10.1248/cpb.c16-00513.
Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI- and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, -13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, -12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NI-loaded and blank cubosomes existed in the cubic space group Im3̄m. The lattice parameters of the SPI- and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI- and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.
采用高压均质技术制备了含有螺内酯（SPI）或硝苯地平（NI）的单油酸甘油酯立方液晶纳米粒，并对其溶解度和口服生物利用度进行了表征。测定了负载SPI和NI的立方液晶纳米粒的平均粒径、多分散指数（PDI）、ζ电位、溶解度和包封率（EE）值，分别为90.4nm、0.187、-13.4mV、163μg/mL和90.2%，以及91.3nm、0.168、-12.8mV、189μg/mL和93.0%，这些值与空白立方液晶纳米粒几乎相同。小角X射线散射分析证实，负载SPI、负载NI和空白立方液晶纳米粒均存在于立方空间群Im3̄m中。负载SPI和NI的立方液晶纳米粒的晶格参数分别为147.6和151.6Å，与空白立方液晶纳米粒（151.0Å）几乎相同。负载SPI和NI的立方液晶纳米粒的体外释放曲线表明，在12-48小时内，它们在各种介质中的药物释放量不到5%，这表明大部分药物仍包裹在其脂质双层的立方相中。此外，体内药代动力学结果表明，与相同材料的纯分散体相比，这些立方液晶纳米粒可显著提高药物的全身口服生物利用度。值得注意的是，稳定性结果表明，这些立方液晶纳米粒的平均粒径和PDI值至少在4周内保持稳定。综上所述，这些结果表明单油酸甘油酯立方液晶纳米粒是提高难溶性药物溶解度和口服生物利用度的有前景的药物载体。
