Sharma D, Chelvi T P, Kaur J, Ralhan R
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Melanoma Res. 1998 Jun;8(3):240-4. doi: 10.1097/00008390-199806000-00006.
Taxol, an antitumour alkaloid which stabilizes microtubules, demonstrates marked activity against several tumours. However, due to its low aqueous solubility, Cremophor EL (polyoxyethylated castor oil) is used as the excipient in pharmaceutical drug preparations of taxol. This has toxic side effects, thereby limiting the clinical use of taxol in cancer therapy. The aim of this study was to design a novel taxol formulation using thermosensitive liposomes in order to eliminate the Cremophor EL vehicle and improve the antitumour activity of taxol by site-specific drug delivery. Temperature-sensitive liposomes encapsulating taxol were prepared using the natural lipids egg phosphatidylcholine and cholesterol in combination with ethanol. The liposomes have a phase transition temperature (Tm) of 43 degrees C. The in vivo efficacy of thermosensitive liposome encapsulated taxol was determined in B16F10 murine melanoma transplanted into C57BI/6 mice in combination with local hyperthermia. A significant reduction in tumour volume and an increase in survival time was observed in tumour-bearing mice treated with a combination of hyperthermia and thermosensitive liposome encapsulated taxol compared with animals treated with an equivalent dose of free taxol with or without hyperthermia. These results suggest that thermosensitive liposome encapsulated taxol in combination with hyperthermia may be useful in improving the therapeutic efficacy of taxol in the treatment of melanoma.
紫杉醇是一种能使微管稳定的抗肿瘤生物碱，对多种肿瘤显示出显著活性。然而，由于其水溶性低，聚氧乙烯蓖麻油（Cremophor EL）被用作紫杉醇药物制剂中的辅料。这具有毒副作用，从而限制了紫杉醇在癌症治疗中的临床应用。本研究的目的是设计一种使用热敏脂质体的新型紫杉醇制剂，以消除聚氧乙烯蓖麻油载体，并通过靶向给药提高紫杉醇的抗肿瘤活性。使用天然脂质蛋黄卵磷脂和胆固醇并结合乙醇制备了包裹紫杉醇的热敏脂质体。这些脂质体的相变温度（Tm）为43℃。在将B16F10小鼠黑色素瘤移植到C57BI/6小鼠体内的实验中，结合局部热疗测定了包裹紫杉醇的热敏脂质体的体内疗效。与接受等量游离紫杉醇加或不加局部热疗的动物相比，接受热疗和包裹紫杉醇的热敏脂质体联合治疗的荷瘤小鼠的肿瘤体积显著减小，存活时间延长。这些结果表明，包裹紫杉醇的热敏脂质体与热疗联合使用可能有助于提高紫杉醇治疗黑色素瘤的疗效。
