School of Pharmacy, West Virginia University, P.O. Box 9500, Morgantown, WV, 26506, USA.
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, 2500 California Plaza, Omaha, NE, 68178, USA.
AAPS PharmSciTech. 2017 Oct;18(7):2814-2823. doi: 10.1208/s12249-017-0772-7. Epub 2017 Apr 10.
Curcumin and resveratrol are naturally occurring polyphenolic compounds having anti-cancer potential. However, their poor aqueous solubility and bioavailability limit their clinical use. Entrapment of hydrophobic drugs into hydrophilic nanoparticles such as calcium alginate presents a means to deliver these drugs to their target site. Curcumin and resveratrol-loaded calcium alginate nanoparticles were prepared by emulsification and cross-linking process. The nanoparticles were characterized for particle size, zeta potential, moisture content, physical state of the drugs, physical stability, and entrapment efficiency. An UPLC method was developed and validated for the simultaneous analysis of curcumin and resveratrol. Alginate nanoformulation was tested for in vitro efficacy on DU145 prostate cancer cells. The particle size of the nanosuspension and freeze-dried nanoparticles was found to be 12.53 ± 1.06 and 60.23 ± 15 nm, respectively. Both DSC and powder XRD studies indicated that curcumin as well as resveratrol were present in a non-crystalline state, in the nanoparticles. The entrapment efficiency for curcumin and resveratrol was found to be 49.3 ± 4.3 and 70.99 ± 6.1%, respectively. Resveratrol showed a higher percentage of release than curcumin (87.6 ± 7.9 versus 16.3 ± 3.1%) in 24 h. Curcumin was found to be taken up by the cells from solution as well as the nanoparticles. Resveratrol had a poor cellular uptake. The drug-loaded nanoparticles exhibit cytotoxic effects on DU145 cells. At high concentration, drug solution exhibited greater toxicity than nanoparticles. The alginate nanoformulation was found to be safe for intravenous administration.
姜黄素和白藜芦醇是具有抗癌潜力的天然多酚化合物。然而,它们较差的水溶性和生物利用度限制了它们的临床应用。将疏水性药物包封到亲水性纳米粒子中,如海藻酸钠,可以将这些药物递送到靶部位。通过乳化和交联过程制备了负载姜黄素和白藜芦醇的海藻酸钠纳米粒子。对纳米粒子的粒径、Zeta 电位、水分含量、药物的物理状态、物理稳定性和包封效率进行了表征。建立并验证了 UPLC 法同时分析姜黄素和白藜芦醇。对海藻酸钠纳米制剂在 DU145 前列腺癌细胞中的体外疗效进行了测试。纳米混悬液和冷冻干燥纳米粒子的粒径分别为 12.53±1.06nm 和 60.23±15nm。DSC 和粉末 XRD 研究均表明,姜黄素和白藜芦醇均以无定形状态存在于纳米粒子中。姜黄素和白藜芦醇的包封效率分别为 49.3±4.3%和 70.99±6.1%。24 小时时,白藜芦醇的释放百分比(87.6±7.9%)高于姜黄素(16.3±3.1%)。姜黄素既可以从溶液中也可以从纳米粒子中被细胞摄取。白藜芦醇的细胞摄取能力较差。载药纳米粒子对 DU145 细胞具有细胞毒性作用。在高浓度下,药物溶液的毒性大于纳米粒子。海藻酸钠纳米制剂静脉注射是安全的。