Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing, 100191, China.
AAPS PharmSciTech. 2010 Jun;11(2):752-9. doi: 10.1208/s12249-010-9430-z. Epub 2010 May 5.
The purpose of this present study was to evaluate the antiangiogenic activity of sterically stabilized liposomes containing paclitaxel (SSL-PTX). The SSL-PTX was prepared by the thin-film method. The release of paclitaxel from SSL-PTX was analyzed using a dialysis method. The effect of SSL-PTX on endothelial cell proliferation and migration was investigated in vitro. The antitumor and antiangiogenic activity of SSL-PTX was evaluated in MDA-MB-231 tumor xenograft growth in BALB/c nude mice. The release of paclitaxel from SSL-PTX was 22% within 24 h. Our in vitro results indicated that SSL-PTX could effectively inhibit the endothelial cell proliferation and migration at a concentration-dependent manner. We also observed that metronomic SSL-PTX induced marked tumor growth inhibition in MDA-MB-231 xenograft model via the antiangiogenic mechanism, unlike that in paclitaxel injection (Taxol) formulated in Cremophor EL (CrEL). Overall, our results suggested that metronomic chemotherapy with low-dose, CrEL-free SSL-PTX should be feasible and effective.
本研究旨在评估载紫杉醇的立体稳定脂质体(SSL-PTX)的抗血管生成活性。SSL-PTX 采用薄膜法制备,采用透析法分析紫杉醇的释放。体外研究 SSL-PTX 对内皮细胞增殖和迁移的影响。在 BALB/c 裸鼠 MDA-MB-231 肿瘤异种移植生长中评价 SSL-PTX 的抗肿瘤和抗血管生成活性。24 小时内,SSL-PTX 中紫杉醇的释放率为 22%。我们的体外结果表明,SSL-PTX 可浓度依赖性地有效抑制内皮细胞的增殖和迁移。我们还观察到,与紫杉醇注射液(Taxol)在 Cremophor EL(CrEL)中的制剂不同,低剂量、无 CrEL 的 SSL-PTX 经时化疗通过抗血管生成机制可显著抑制 MDA-MB-231 异种移植模型中的肿瘤生长。总的来说,我们的结果表明,低剂量、无 CrEL 的 SSL-PTX 的节拍化疗应该是可行且有效的。