Russell Berrie Nanotechnology Institute, Technion, Israel Institute of Technology, Haifa, Israel.
Eur J Pharm Biopharm. 2012 Feb;80(2):298-305. doi: 10.1016/j.ejpb.2011.10.022. Epub 2011 Nov 9.
We studied a potential drug delivery system comprising the hydrophobic anticancer drug paclitaxel entrapped within β-casein (β-CN) nanoparticles and its cytotoxicity to human gastric carcinoma cells. Paclitaxel was entrapped by stirring its dimethyl sulfoxide (DMSO) solution into PBS containing β-CN. Cryo-TEM analysis revealed drug nanocrystals, the growth of which was blocked by β-CN. Entrapment efficiency was nearly 100%, and the nanovehicles formed were colloidally stable. Following encapsulation and simulated digestion with pepsin (2 hours at pH=2, 37 °C), paclitaxel retained its cytotoxic activity to human N-87 gastric cancer cells; the IC(50) value (32.5 ± 6.2 nM) was similar to that of non-encapsulated paclitaxel (25.4 ± 2.6 nM). Without prior simulated gastric digestion, β-CN-paclitaxel nanoparticles were non-cytotoxic, suggesting the lack of untoward toxicity to bucal and esophageal epithelia. We conclude that β-CN shows promise to be useful for target-activated oral delivery of hydrophobic chemotherapeutics in the treatment of gastric carcinoma, one of the leading causes of cancer mortality worldwide.
我们研究了一种潜在的药物传递系统，该系统由包埋在β-酪蛋白（β-CN）纳米粒子中的疏水性抗癌药物紫杉醇和其对人胃癌细胞的细胞毒性组成。将紫杉醇的二甲基亚砜（DMSO）溶液搅拌到含有β-CN 的 PBS 中，从而将紫杉醇包埋在其中。冷冻透射电子显微镜（Cryo-TEM）分析显示药物纳米晶体，其生长被β-CN 阻断。包封效率接近 100％，形成的纳米载体具有胶体稳定性。包封后用胃蛋白酶（pH=2，37°C 下 2 小时）进行模拟消化，紫杉醇保留了对人 N-87 胃癌细胞的细胞毒性；IC（50）值（32.5±6.2 nM）与未包封的紫杉醇（25.4±2.6 nM）相似。未经预先模拟的胃消化，β-CN-紫杉醇纳米颗粒无细胞毒性，表明对口腔和食管上皮没有不良毒性。我们得出结论，β-CN 有望成为治疗胃癌（全球癌症死亡率的主要原因之一）的靶向激活口服传递疏水性化疗药物的有用载体。
