State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
Int J Nanomedicine. 2012;7:4499-510. doi: 10.2147/IJN.S32817. Epub 2012 Aug 14.
Paclitaxel, a widely used antitumor agent, has limited clinical application due to its hydrophobicity and systemic toxicity. To achieve sustained and targeted delivery of paclitaxel to tumor sites, liposomes composed of egg phosphatidylcholine, cholesterol, and distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) (PEG(2000)) were prepared by a lipid film method. In addition, the liposomes also contained truncated fibroblast growth factor fragment-PEG-cholesterol as a ligand targeting the tumor marker fibroblast growth factor receptor. Physicochemical characteristics, such as particle size, zeta potential, entrapment efficiency, and release profiles were investigated. Pharmacokinetics and biodistribution were evaluated in C57BL/6 J mice bearing B16 melanoma after intravenous injection of paclitaxel formulated in Cremophor EL (free paclitaxel), conventional liposomes (CL-PTX), or in targeted PEGylated liposomes (TL-PTX).
Compared with CL-PTX and free paclitaxel, TL-PTX prolonged the half-life of paclitaxel by 2.01-fold and 3.40-fold, respectively, in plasma and improved the AUC(0→t) values of paclitaxel by 1.56-fold and 2.31-fold, respectively, in blood. Biodistribution studies showed high accumulation of TL-PTX in tumor tissue and organs containing the mononuclear phagocyte system (liver and spleen), but a considerable decrease in other organs (heart, lung, and kidney) compared with CL-PTX and free paclitaxel.
The truncated fibroblast growth factor fragment-conjugated PEGylated liposome has promising potential as a long-circulating and tumor-targeting carrier system.
紫杉醇是一种广泛应用的抗肿瘤药物，但由于其疏水性和全身毒性，其临床应用受到限制。为了实现紫杉醇对肿瘤部位的持续和靶向递送，采用脂质体薄膜法制备了由卵磷酯、胆固醇和二硬脂酰基磷脂酰乙醇胺-N-聚（乙二醇）（PEG（2000））组成的脂质体。此外，脂质体还含有作为肿瘤标志物成纤维细胞生长因子受体靶向配体的截短型成纤维细胞生长因子片段-PEG-胆固醇。考察了粒径、Zeta 电位、包封率和释放特性等理化特性。在静脉注射用聚氧乙烯蓖麻油（游离紫杉醇）、普通脂质体（CL-PTX）或靶向 PEG 化脂质体（TL-PTX）后，在携带 B16 黑色素瘤的 C57BL/6 J 小鼠中评估了药代动力学和生物分布。
与 CL-PTX 和游离紫杉醇相比，TL-PTX 分别使紫杉醇在血浆中的半衰期延长了 2.01 倍和 3.40 倍，使紫杉醇在血液中的 AUC（0→t）值分别提高了 1.56 倍和 2.31 倍。生物分布研究表明，与 CL-PTX 和游离紫杉醇相比，TL-PTX 在肿瘤组织和包含单核吞噬细胞系统的器官（肝和脾）中高度积聚，但在其他器官（心、肺和肾）中的积聚明显减少。
截短型成纤维细胞生长因子片段缀合的 PEG 化脂质体具有作为长循环和肿瘤靶向载体系统的潜在应用前景。
