Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
Int J Nanomedicine. 2012;7:651-61. doi: 10.2147/IJN.S26538. Epub 2012 Feb 8.
Realizing the therapeutic benefits of quercetin is mostly hampered by its low water solubility and poor absorption. In light of the advantages of nanovehicles in the delivery of flavanoids, we aimed to deliver quercetin perorally with nanomicelles made from the diblock copolymer, polyethylene glycol (PEG)-derivatized phosphatidylethanolamine (PE).
Quercetin-loaded nanomicelles were prepared by using the film casting method, and were evaluated in terms of drug incorporation efficiency, micelle size, interaction with Caco-2 cells, and anticancer activity in the A549 lung cancer cell line and murine xenograft model.
The incorporation efficiency into the nanomicelles was ≥88.9% when the content of quercetin was up to 4% w/w, with sizes of 15.4-18.5 nm and polydispersity indices of <0.250. Solubilization of quercetin by the nanomicelles increased its aqueous concentration by 110-fold. The quercetin nanomicelles were stable when tested in simulated gastric (pH 1.2) and intestinal (pH 7.4) fluids, and were non-toxic to the Caco-2 cells as reflected by reversible reduction in transepithelial electrical resistance and ≤25% lactose dehydrogenase release. The anticancer activity of quercetin could be significantly improved over the free drug through the nanomicellar formulation when tested using the A549 cancer cell line and murine xenograft model. The nanomicellar quercetin formulation was well tolerated by the tumor-bearing animals, with no significant weight loss observed at the end of the 10-week study period.
A stable PEG-PE nanomicellar formulation of quercetin was developed with enhanced peroral anticancer activity and no apparent toxicity to the intestinal epithelium.
黄酮类化合物的递送中纳米载体的优势在于，我们旨在通过二嵌段共聚物聚乙二醇（PEG）衍生的磷脂酰乙醇胺（PE）制成的纳米胶束经口递delivery 给予 quercetin。
采用薄膜分散法制备载药纳米胶束，并从载药效率、胶束粒径、与 Caco-2 细胞的相互作用以及在 A549 肺癌细胞系和小鼠异种移植模型中的抗癌活性等方面对其进行评价。
当 quercetin 的含量高达 4%（w/w）时，纳米胶束的包封效率≥88.9%，粒径为 15.4-18.5nm，多分散指数<0.250。纳米胶束对 quercetin 的增溶作用使其在水溶液中的浓度增加了 110 倍。当在模拟胃液（pH 1.2）和肠液（pH 7.4）中进行测试时，quercetin 纳米胶束稳定，对 Caco-2 细胞无毒性，表现为跨上皮电阻可逆降低和≤25%的乳糖脱氢酶释放。与游离药物相比，通过纳米胶束制剂，quercetin 的抗癌活性在 A549 癌细胞系和小鼠异种移植模型中可以得到显著提高。在 10 周的研究结束时，荷瘤动物对纳米胶束 quercetin 制剂的耐受性良好，未观察到明显的体重减轻。
开发了一种稳定的 PEG-PE 纳米胶束制剂，具有增强的口服抗癌活性，对肠上皮无明显毒性。
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