Vaccine Research Institute of San Diego (VRISD), San Diego Science Center, San Diego, California, USA.
Biomed Res Int. 2018 Nov 11;2018:9035452. doi: 10.1155/2018/9035452. eCollection 2018.
Plumbagin, a medicinal plant-derived 5-hydroxy-2-methyl-1,4-naphthoquinone, is an emerging drug with a variety of pharmacological effects, including potent anticancer activity. We have previously shown that plumbagin improves the efficacy of androgen deprivation therapy (ADT) in prostate cancer and it is now being evaluated in phase I clinical trial. However, the development of formulation of plumbagin as a compound with sparing solubility in water is challenging.
We have formulated plumbagin-loaded nanoemulsion using pneumatically controlled high pressure homogenization of oleic acid dispersions with polyoxyethylene (20) sorbitan monooleate as surfactant. Nanoemulsion formulations were characterized for particle size distribution by dynamic light scattering (DLS). The kinetics of drug release was determined by equilibrium dialysis. Anticancer activity toward prostate cancer cells PTEN-P2 was assessed by MTS (Owen's reagent) assay.
Particle size distribution of nanoemulsions is tunable and depends on the surfactant concentration. Nanoemulsion formulations of plumbagin with 1-3.5% (w/w) of surfactant showed robust stability of size distribution over time. Plumbagin-loaded nanoemulsion with average hydrodynamic diameter of 135 nm showed exponential release of plumbagin with a half-life of 6.1 h in simulated gastric fluid, 7.0 h in simulated intestinal fluid, and displayed enhanced antiproliferative effect toward prostate cancer cells PTEN-P2 compared to free plumbagin.
High drug-loading capacity, retention of nanoparticle size, kinetics of release under simulated physiological conditions, and increased antiproliferative activity indicate that oleic-acid based nanoemulsion formulation is a suitable delivery system of plumbagin.
百折不挠，一种药用植物衍生的 5-羟基-2-甲基-1,4-萘醌，是一种新兴的药物，具有多种药理作用，包括强大的抗癌活性。我们之前已经表明，百折不挠可以提高前列腺癌去势治疗（ADT）的疗效，目前正在进行 I 期临床试验。然而，将百折不挠制成水溶性差的化合物制剂具有挑战性。
我们使用气动控制高压匀化油酸分散体，用聚氧乙烯（20）山梨醇单油酸酯作为表面活性剂，制备了负载百折不挠的纳米乳液。通过动态光散射（DLS）对纳米乳液制剂的粒径分布进行了表征。通过平衡透析法测定药物释放动力学。通过 MTS（欧文试剂）测定法评估对前列腺癌细胞 PTEN-P2 的抗癌活性。
纳米乳液的粒径分布是可调的，取决于表面活性剂的浓度。含有 1-3.5%（w/w）表面活性剂的百折不挠纳米乳液制剂在长时间内具有稳定的粒径分布。平均水动力直径为 135nm 的百折不挠负载纳米乳液呈指数释放百折不挠，在模拟胃液中的半衰期为 6.1h，在模拟肠液中的半衰期为 7.0h，与游离百折不挠相比，对前列腺癌细胞 PTEN-P2 的增殖抑制作用增强。
高载药量、纳米颗粒尺寸保持、模拟生理条件下的释放动力学以及增强的增殖抑制活性表明，油酸基纳米乳液制剂是百折不挠的一种合适的递送系统。
