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Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity

Nature Medicine volume 8, pages 81–84 (2002)Cite this article

Abstract

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.

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Figure 1: Cytotoxicity towards human ovarian carcinoma cells.
Figure 2: Nanocapsules of cisplatin: isolation and characterization.
Figure 3: Cytotoxicity and sizing of nanocapsules of cisplatin.
Figure 4: Mechanism of nanocapsule formation and cell interaction.

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Acknowledgements

We thank N. Jelluma, V. Chupin and W. Mulder for experimental support, J. Reedijk and T. de Kroon for helpful discussions, and the Dutch Cancer Society (N.K.B.) for financial support (project UU2001-2493).

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Authors and Affiliations

  1. Department Biochemistry of Membranes, Center for Biomembranes and Lipid Enzymology, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands

    Koert N.J. Burger, Rutger W.H.M. Staffhorst, Hanke C. de Vijlder, Maria J. Velinova & Ben de Kruijff

  2. Department of Pathology, EM Unit, University of Limburg, Maastricht, The Netherlands

    Paul H. Bomans & Peter M. Frederik

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  1. Koert N.J. Burger
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  2. Rutger W.H.M. Staffhorst
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Correspondence to Koert N.J. Burger.

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Burger, K., Staffhorst, R., de Vijlder, H. et al. Nanocapsules: lipid-coated aggregates of cisplatin with high cytotoxicity. Nat Med 8, 81–84 (2002). https://doi.org/10.1038/nm0102-81

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