Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, South Dakota 57007, United States.
Mol Pharm. 2012 Sep 4;9(9):2778-86. doi: 10.1021/mp2006455. Epub 2012 Jul 26.
Novel biodegradable micelles were synthesized by conjugating methoxy poly(ethylene glycol) (mPEG) to zein, a biodegradable hydrophobic plant protein. The mPEG-zein micelles were in the size range of 95-125 nm with a low CMC (5.5 × 10(-2) g/L). The micelles were nonimmunogenic and were stable upon dilution with buffer as well as 10% serum. Curcumin, an anticancer agent with multiple delivery challenges, was encapsulated in mPEG-zein micelles. The micelles significantly enhanced the aqueous solubility (by 1000-2000-fold) and stability (by 6-fold) of curcumin. PEG-zein micelles sustained the release of curcumin up to 24 h in vitro. Curcumin-loaded mPEG-zein micelles showed significantly higher cell uptake than free curcumin in drug-resistant NCI/ADR-RES cancer cells in vitro. Micellar curcumin formulation was more potent than free curcumin in NCI/ADR-RES cancer cells, as evidenced from the 3-fold reduction in IC(50) value of curcumin. Overall, this study for the first time reports a natural protein core based polymeric micelle and demonstrates its application for the delivery of hydrophobic anticancer drugs such as curcumin.
新型可生物降解胶束通过将甲氧基聚乙二醇（mPEG）与玉米醇溶蛋白（一种可生物降解的疏水性植物蛋白）偶联合成。mPEG-玉米醇溶蛋白胶束的粒径范围为 95-125nm，CMC 较低（5.5×10(-2)g/L）。胶束无免疫原性，在缓冲液和 10%血清稀释时稳定。姜黄素是一种具有多种给药挑战的抗癌药物，被包裹在 mPEG-玉米醇溶蛋白胶束中。胶束显著提高了姜黄素的水溶解度（提高了 1000-2000 倍）和稳定性（提高了 6 倍）。PEG-玉米醇溶蛋白胶束在体外可将姜黄素的释放延长至 24 小时。与游离姜黄素相比，载姜黄素的 mPEG-玉米醇溶蛋白胶束在耐药性 NCI/ADR-RES 癌细胞中的细胞摄取率显著提高。胶束姜黄素制剂在 NCI/ADR-RES 癌细胞中的效力比游离姜黄素更高，这从姜黄素 IC50 值降低了 3 倍得到证实。总之，该研究首次报道了一种基于天然蛋白核的聚合物胶束，并展示了其在疏水性抗癌药物（如姜黄素）递送上的应用。
