Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity
Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity
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DOI：
10.1038/nm0102-81
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发表时间：
2002-01-01
期刊：
影响因子：
82.9
通讯作者：
de Kruijff, B
中科院分区：
文献类型：
--
作者：
Burger, KNJ;Staffhorst, RWHM;de Kruijff, B
顺铂是治疗实体瘤最广泛使用的药物之一，但其临床应用受到毒性的限制。顺铂的低水溶性和低亲脂性阻碍了顺铂的低毒性脂质体制剂的开发，导致包封效率非常低。我们描述了一种新方法，可以将顺铂有效封装在脂质制剂中；它基于在带负电荷的磷脂存在下反复冷冻和解冻顺铂浓缩溶液。该方法的独特之处在于它生成纳米胶囊，其中顺铂的小聚集体被单个脂质双层覆盖。纳米胶囊具有前所未有的药物脂质比，其体外细胞毒性比游离药物高出1000倍。对纳米胶囊形成机制的分析表明，该方法可以推广到其他表现出低水溶性和亲脂性的药物。
Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinical utility is limited by toxicity. The development of less toxic, liposomal formulations of cisplatin has been hampered by the low water solubility and low lipophilicity of cisplatin, resulting in very low encapsulation efficiencies. We describe a novel method allowing the efficient encapsulation of cisplatin in a lipid formulation; it is based on repeated freezing and thawing of a concentrated solution of cisplatin in the presence of negatively charged phospholipids. The method is unique in that it generates nanocapsules, which area small aggregates of cisplatin covered by a single lipid bilayer. The nanocapsules have an unprecedented drug-to-lipid ratio and an in vitro cytotoxicity up to 1000-fold higher than the free drug. Analysis of the mechanism of nanocapsule formation suggests that the method may be generalized to other drugs showing low water solubility and lipophilicity.