Liposome Formulation of Paclitaxel with Enhanced Solubility and Stability
Liposome Formulation of Paclitaxel with Enhanced Solubility and Stability
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DOI：
10.1080/10717540601098799
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发表时间：
2007-01
期刊：
影响因子：
6
通讯作者：
Tao Yang;F. Cui;Min‐Koo Choi;Hongxia Lin;S. Chung;C. Shim;Dae-Duk Kim
中科院分区：
文献类型：
--
作者：
Tao Yang;F. Cui;Min‐Koo Choi;Hongxia Lin;S. Chung;C. Shim;Dae-Duk Kim
尽管紫杉醇（Taxol®）具有强的抗肿瘤活性，但由于其低水溶性和由Cremophor® EL和乙醇（其为当前商业产品中使用的媒介物）引起的超敏反应，其临床应用有限。在开发可替代Taxol®的药学上可接受的制剂的尝试中，已经构建了掺入紫杉醇的脂质体以改善溶解度和物理化学稳定性。系统考察了脂质体中胆固醇和脂质体成分对紫杉醇溶解度和包封率的影响。结果表明，脂质体水合介质中5%（v/v）的聚乙二醇400显著增加了溶解度（高达3.39 mg/mL）以及由10%（w/v）的S100 PC与胆固醇（胆固醇与脂质摩尔比= 10：90）组成的脂质体制剂中的EE和紫杉醇含量。当蔗糖（糖脂摩尔比= 2.3）作为冻干保护剂在脂质体的冷冻干燥过程中，脂质体的物理化学稳定性显着提高。此外，最终脂质体制剂对MDA-MB-231人乳腺癌细胞系的细胞毒性与Taxol®的细胞毒性没有显著差异。本研究中开发的脂质体制剂中紫杉醇的水溶性增强以及物理化学稳定性可能是Cremophor® EL和乙醇制剂的更安全有效的替代品。
Despite its strong antitumor activity, paclitaxel (Taxol®) has limited clinical applications due to its low aqueous solubility and hypersensitivity caused by Cremophor® EL and ethanol which is the vehicle used in the current commercial product. In an attempt to develop a pharmaceutically acceptable formulation that could replace Taxol®, a paclitaxel incorporated liposome has been constructed to improve solubility and physicochemical stability. The effect of various components of the liposome, including cholesterol and lipid, on the solubility and entrapment efficiency (EE) of paclitaxel was systematically investigated. The results showed that 5% (v/v) of polyethylene glycol 400 in the hydration medium of liposome significantly increased the solubility (up to 3.39 mg/mL) as well as the EE and the paclitaxel content in the liposome formulation composed of 10% (w/v) of S100PC with cholesterol (cholesterol-to-lipid molar ratio = 10:90). When sucrose (sugar-to-lipid molar ratio = 2.3) was added as a lyoprotectant during the freeze-drying of the liposome, physicochemical stability of liposome was significantly improved. Moreover, the cytotoxicity of the final liposome formulation against MDA-MB-231 human breast cancer cell line was not significantly different from that of Taxol®. The enhanced aqueous solubility as well as the physicochemical stability of paclitaxel in the liposome formulation developed in this study could be a safer and effective alternative to the Cremophor® EL and ethanol formulation.