Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity

• Published in: Nature medicine Vol. 8; no. 1; pp. 81 - 84
• Main Authors: Burger, Koert N.J, Staffhorst, Rutger W.H.M, de Vijlder, Hanke C, Velinova, Maria J, Bomans, Paul H, Frederik, Peter M, de Kruijff, Ben
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-01-2002
• Subjects: Aggregates; Antineoplastic Agents - therapeutic use; Carcinoma - drug therapy; Cisplatin - therapeutic use; Cytotoxicity; Dose-Response Relationship, Drug; Drug Compounding - methods; Female; Freezing; Humans; Liposomes; Nanotechnology - methods; Ovarian Neoplasms - drug therapy; Particle Size; Solubility; Thawing; Tumor Cells, Cultured
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm0102-81

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 are 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.