Sharma A, Straubinger R M, Ojima I, Bernacki R J
Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
J Pharm Sci. 1995 Dec;84(12):1400-4. doi: 10.1002/jps.2600841204.
Taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere) are promising agents for use against ovarian cancer and other malignancies. Recently, SB-T-1011, a semisynthetic taxane, has been prepared from 14-hydroxy-10-deacetylbaccatin III. SB-T-1011 shows similar or greater in vitro cytostatic activity than paclitaxel, depending on the tumor cell line. The administration of taxanes is problematic due to their low solubility in most pharmaceutically acceptable solvents; formulations used clinically contain Cremophor/ethanol (diluent 12) or polysorbate 80/ethanol, excipients which may cause serious adverse effects. To eliminate these vehicles, we have prepared paclitaxel liposome formulations. The objective of the present work was to evaluate the antitumor activity of paclitaxel and two semisynthetic analogs in Cremophor-based and liposomal formulations. Antitumor activity was evaluated against A121a, a taxane-sensitive human ovarian tumor, growing as subcutaneous xenografts in athymic nude mice. Free and liposomal formulations of each taxane showed similar antitumor effect. The antitumor activity of paclitaxel and SB-T-1011 was similar, and docetaxel was more potent than either paclitaxel or SB-T-1011. Overall, taxane liposomes were better tolerated and more easily administered iv than taxane formulated in Cremophor/ethanol.
紫杉烷类药物如紫杉醇（泰素）和多西他赛（泰索帝）是用于治疗卵巢癌和其他恶性肿瘤的有前景的药物。最近，一种半合成紫杉烷SB-T-1011已由14-羟基-10-去乙酰巴卡亭III制备而成。根据肿瘤细胞系的不同，SB-T-1011在体外显示出与紫杉醇相似或更强的细胞生长抑制活性。由于紫杉烷类药物在大多数药学可接受溶剂中的溶解度较低，其给药存在问题；临床使用的制剂含有聚氧乙烯蓖麻油/乙醇（稀释剂12）或聚山梨酯80/乙醇，这些辅料可能会引起严重的不良反应。为了去除这些载体，我们制备了紫杉醇脂质体制剂。本研究的目的是评估紫杉醇和两种半合成类似物在基于聚氧乙烯蓖麻油的制剂和脂质体制剂中的抗肿瘤活性。针对A121a（一种对紫杉烷敏感的人卵巢肿瘤，在无胸腺裸鼠皮下作为异种移植物生长）评估了抗肿瘤活性。每种紫杉烷的游离制剂和脂质体制剂显示出相似的抗肿瘤效果。紫杉醇和SB-T-1011的抗肿瘤活性相似，多西他赛比紫杉醇或SB-T-1011更有效。总体而言，与用聚氧乙烯蓖麻油/乙醇配制的紫杉烷相比，紫杉烷脂质体耐受性更好，静脉给药更容易。
