Li C, Yu D, Inoue T, Yang D J, Milas L, Hunter N R, Kim E E, Wallace S
Division of Diagnostic Imaging, University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
Anticancer Drugs. 1996 Aug;7(6):642-8. doi: 10.1097/00001813-199608000-00004.
Water-soluble paclitaxel may cause less side effects and be less costly to administer in comparison to a taxol formulation using a cremophor EL/alcohol vehicle. In this study, polyethylene glycol (PEG; MW 5000) was conjugated to the 2' position of paclitaxel through a spacer succinyl group. PEG-paclitaxel as a non-ionic paclitaxel prodrug was highly water soluble (> 20 mg equiv. paclitaxel/ml). The release of paclitaxel from phosphate-buffered solution was pH dependent. The half-life of PEG-paclitaxel was 7.6, 54 and 311 min at pH 9.0, 7.4 and 6.0, respectively. PEG-paclitaxel inhibited the growth of B16 melanoma cells to an extent similar to that of paclitaxel. In MCA-4 mammary tumor-bearing mice, a single dose of PEG-paclitaxel (40 mg equiv. paclitaxel/kg body weight) significantly delayed tumor growth. The average number of days for the tumor to reach 12 from 8 mm in diameter increased from 6.5 days for control animals to 8.5 days for PEG-paclitaxel-treated animals and 9.4 days for paclitaxel-treated animals. These studies demonstrated that PEG may be used as an effective solubilizing carrier for paclitaxel.
与使用聚氧乙烯蓖麻油/乙醇载体的紫杉醇制剂相比，水溶性紫杉醇可能产生较少的副作用，且给药成本较低。在本研究中，聚乙二醇（PEG；分子量5000）通过间隔琥珀酰基与紫杉醇的2'位共轭。PEG-紫杉醇作为一种非离子型紫杉醇前药具有高度水溶性（>20 mg紫杉醇当量/ml）。紫杉醇从磷酸盐缓冲溶液中的释放依赖于pH值。PEG-紫杉醇在pH 9.0、7.4和6.0时的半衰期分别为7.6、54和311分钟。PEG-紫杉醇对B16黑色素瘤细胞生长的抑制程度与紫杉醇相似。在携带MCA-4乳腺肿瘤的小鼠中，单剂量的PEG-紫杉醇（40 mg紫杉醇当量/千克体重）显著延迟了肿瘤生长。肿瘤直径从8毫米长到12毫米的平均天数，对照动物为6.5天，PEG-紫杉醇处理的动物为8.5天，紫杉醇处理的动物为9.4天。这些研究表明，PEG可作为紫杉醇的有效增溶载体。
