A folate receptor-targeted emulsion formulation for paclitaxel.
A folate receptor-targeted emulsion formulation for paclitaxel.
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发表时间：
2003-11
影响因子：
2
通讯作者：
P. J. Stevens;Robert J. Lee
中科院分区：
文献类型：
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作者：
P. J. Stevens;Robert J. Lee
目的本研究旨在配制和体外评估叶酸受体（FR）靶向乳剂，作为亲脂性药物紫杉醇的载体，在 FR 过表达的肿瘤细胞中。材料和方法 FR 靶向紫杉醇乳剂 (< 100 nm)，由 Tween-80:三油酸甘油酯:胆固醇:油酸:蛋磷脂酰胆碱 (EPC) (10:30:19.5:30:10) 组成，含 0.5 摩尔 % 的叶酸-聚乙二醇-胆固醇或采用乙醇注射法制备聚乙二醇二硬脂酰磷脂酰乙醇胺(PEG-DSPE)。通过在 4 摄氏度和 25 摄氏度下颗粒尺寸的变化以及不同时间点的药物保留来监测乳液的稳定性。 FR 靶向制剂的 IC50 在 FR+ KB 细胞中体外测定。结果 通过乙醇注射制备了稳定的靶向乳剂，包封了大于 70% 的紫杉醇，平均直径 < 100 nm。 FR 靶向乳液的体外细胞毒性测定在 KB 细胞中的 IC50 为 0.13 microM。靶向乳液和非靶向乳液之间的 IC50 值存在显着差异。结论 含有亲脂性药物紫杉醇的 FR 靶向乳剂能够在培养的 KB 细胞中特异性结合受体，值得在体内进行进一步研究。本文是首篇关于FR靶向乳剂型药物载体的报道。此外，还提出了纳米颗粒制剂（例如这些乳液）的体内抗肿瘤活性的新机制，该机制基于其抗血管生成作用。
PURPOSE This study was aimed at the formulation and an in vitro evaluation of folate receptor (FR)-targeted emulsions as carriers for the lipophilic drug paclitaxel, in FR-overexpressing tumor cells. MATERIALS AND METHODS FR-targeted paclitaxel emulsions (< 100 nm) composed of Tween-80:triolein:cholesterol:oleic acid:egg-phosphatidylcholine (EPC) (10:30:19.5:30:10), with 0.5 mole % of folate-polyethyleneglycol-cholesterol or polyethyleneglycol-distearoylphosphatidylethanolamine (PEG-DSPE), were prepared by ethanol injection method. Stability of the emulsions was monitored by changes in particle size while at 4 degrees C and 25 degrees C, and drug retention at various time-points. IC50 of the FR-targeted formulations was determined in vitro in the FR+ KB cells. RESULTS Stable targeted emulsions were prepared by ethanol injection encapsulating greater than 70 percent of paclitaxel, having a mean diameter < 100 nm. In vitro cytotoxicity assay on the FR-targeted emulsions gave IC50 of 0.13 microM in KB cells. There was a significant difference in the IC50 values between the targeted emulsions and those that were non-targeted. CONCLUSION FR-targeted emulsions incorporating the lipophilic drug paclitaxel were capable of specific receptor binding in cultured KB cells and warrant further investigation in vivo. This article is the first report on an FR-targeted emulsion-type drug carrier. Furthermore, a novel mechanism for in vivo antitumor activity of nanoparticular formulations, such as these emulsions, that is based on their antiangiogenic effect is proposed.