Department of Pharmaceutical Engineering, College of Pharmacy, Shandong University, Jinan, China.
Int J Nanomedicine. 2012;7:151-62. doi: 10.2147/IJN.S27639. Epub 2012 Jan 9.
The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS) with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells.
Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol) used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research.
The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor(®) EL, 32.5% Transcutol(®) HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100). The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular uptake studies analyzed with fluorescence microscopy and flow cytometry indicated that the FSMEDDS formulation could efficiently bind with the folate receptors on the surface of positive folate receptors cell lines. In addition, FSMEDDS showed greater cytotoxicity than SMEDDS in the above two cells.
FSMEDDS-filled colon-targeted capsules are a potential carrier for colon delivery of curcumin.
本研究旨在制备、表征并评价叶酸修饰的自微乳给药系统（FSMEDDS），以提高姜黄素的溶解度并将其递送至结肠，促进叶酸受体介导的 FSMEDDS 内吞进入结肠癌细胞。
构建三元相图以获得最有效的自乳化区域，并通过单纯形格子实验设计优化载姜黄素的 SMEDDS 配方。然后，将三种疏水性叶酸衍生物（叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺、叶酸-聚乙二醇-胆固醇琥珀酸酯和叶酸-聚乙二醇-胆固醇）用作表面活性剂添加到载姜黄素的 SMEDDS 制剂中。使用大鼠原位结肠灌流法优化 FSMEDDS 的配方。然后将载姜黄素的 FSMEDDS 填充到结肠靶向胶囊中，并研究其体外释放情况。本研究还进行了细胞毒性研究和细胞摄取研究。
通过建立的大鼠原位结肠灌流法优化的 FSMEDDS 的最佳配方由 57.5%的 Cremophor®EL、32.5%的 Transcutol®HP、10%的 Capryol™90 和少量的叶酸-聚乙二醇-胆固醇琥珀酸酯（叶酸材料与 Cremophor EL 的重量比为 1:100）组成。体外释放结果表明，所得到的姜黄素制剂可以有效地到达结肠并立即释放药物。荧光显微镜和流式细胞术分析的细胞摄取研究表明，FSMEDDS 制剂可以有效地与阳性叶酸受体细胞系表面的叶酸受体结合。此外，FSMEDDS 在上述两种细胞中的细胞毒性大于 SMEDDS。
载姜黄素的 FSMEDDS 填充结肠靶向胶囊是一种用于结肠递药的潜在载体。
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