Dabholkar Rupa D, Sawant Rishikesh M, Mongayt Dimitriy A, Devarajan Padma V, Torchilin Vladimir P
Department of Pharmaceutical Sciences, University Institute of Chemical Technology, Mumbai, Maharashtra, India.
Int J Pharm. 2006 Jun 6;315(1-2):148-57. doi: 10.1016/j.ijpharm.2006.02.018. Epub 2006 Mar 6.
Mixed micelles prepared of poly(ethylene glycol)2000-phosphatidyl ethanolamine conjugate (PEG(2000)-PE) and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in 1:1 molar ratio have been investigated. Micelle formation was confirmed by NMR spectroscopy. CMC of the micelles was found to be 1.5 x 10(-5)M. Poorly soluble anti-cancer drug paclitaxel (PCL) was efficiently solubilized in 15 nm non-toxic PEG-PE/TPGS micelles. PCL entrapment was quite stable with only about 20% of the incorporated drug released from micelles after 48 h at 37 degrees C. In addition, PCL-containing PEG(2000)-PE/TPGS micelles were stable in vitro under various conditions modeling the physiological ones, in particular, at low pH values and in the presence of bile acids, which is especially important for their possible oral administration. Fluorescently labeled micelles demonstrated time-dependent internalization by human colon adenocarcinoma cell line, Caco-2. The internalization of PEG(2000)-PE/TPGS micelles loaded with P-glycoprotein (P-gp) substrate, rhodamine-123 (RH-123), opposite to the internalization of the free RH-123, was not influenced by the inhibition of the P-gp pump with verapamil hydrochloride, which assumes a P-gp-independent micelle internalization.
对由聚乙二醇2000 - 磷脂酰乙醇胺共轭物（PEG(2000)-PE）和d-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）按1:1摩尔比制备的混合胶束进行了研究。通过核磁共振光谱证实了胶束的形成。发现该胶束的临界胶束浓度为1.5×10⁻⁵M。难溶性抗癌药物紫杉醇（PCL）能有效地溶解在15纳米的无毒PEG-PE/TPGS胶束中。PCL的包封相当稳定，在37℃下48小时后，只有约20%的包封药物从胶束中释放出来。此外，含PCL的PEG(2000)-PE/TPGS胶束在模拟生理条件的各种体外条件下是稳定的，特别是在低pH值和胆汁酸存在的情况下，这对于它们可能的口服给药尤为重要。荧光标记的胶束显示出对人结肠腺癌细胞系Caco-2的时间依赖性内化作用。与游离罗丹明-123（RH-123）的内化作用相反，装载有P-糖蛋白（P-gp）底物RH-123的PEG(2000)-PE/TPGS胶束的内化作用不受盐酸维拉帕米对P-gp泵的抑制影响，这表明胶束的内化作用不依赖于P-gp。
