Liposomes were discovered in the 1960ies by A.D. Bangham and since then they became very versatile tools in biology, biochemistry and medicine. Liposomes are the smallest artificial vesicles of spherical shape that can be produced from natural nontoxic phospholipids and cholesterol. As shown in the following schematic drawings of liposomes, the vesicles can be used as drug carriers and loaded with a great variety of molecules, such as small drug molecules, proteins, nucleotides and even plasmids. Liposomes are extremely versatile and due to the variability of their composition as shown below in a figure which we adapted from Science-Medicine they can be used for a large number of applications.
As shown in the following figure, we use the liposomes as carriers for lipophilic drugs like the antitumor drug NOAC and antiviral derivatives of AZT and ddC which are firmly incorporated into the membrane bilayer of the liposomes.
For medical applications as drug carriers the liposomes can be injected intravenously and when they are modified with lipids which render their surface more hydrophilic, e.g. pegylated phospholipids, their circulation time in the bloodstream can be increased significantly. Such so called "stealth" liposomes are especially being used as carriers for hydrophilic (water soluble) anticancer drugs like doxorubicin, mitoxantrone and many others.
To further improve the specific binding properties of a drug-carrying liposome to a target cell, - such as a tumor cell -, specific molecules (antibodies, proteins, peptides etc.) are attached on their surface. The following electron micrograph shows the surface of a tumor cell to which a large number of tumorcell-specific liposomes are tightly bound:
Other publications from the Laboratory of Liposome Research:
Rentsch, K.M., Schwendener, R.A., Hänseler, E. Determination of mitoxantrone in mouse whole blood and different tissues by high-performance liquid chromatography. J. Chromatogr. B, 679: 185-192, 1996.
Schott, H., Ludwig, P.S., Gansauge, F., Gansauge, S., Schwendener, R.A. Synthesis and in vitro antitumor activity of 2'-deoxy-5-fluorouridylyl-(3'-5')-2'-deoxy-5-fluoro-N4-octadecylcytidine: A new amphiphilic dinucleoside phosphate. Liebigs Annalen der Chemie, 413-417, 1997.
Rentsch, K.M., Horber, D.H., Schwendener, R.A., Wunderli-Allenspach, H., Hänseler, E. Comparative pharmacokinetic and cytotoxic analysis of three different formulations of mitoxantrone in mice. Br. J. Cancer, 75: 986-992, 1997.
Frankenberger, M., Hofmann, B., Emmerich, B., Nerl, C., Schwendener, R.A., Ziegler-Heitbrock, H.W.L. Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukemia cells. Br. J. Haematol.98: 186-194, 1997.
Seiler, P., Aichele, P., Odermatt, B., Hengartner, H., Zinkernagel, R.M., Schwendener, R.A. Clearance of infection with lymphocytic choriomeningitis virus depends on splenic marginal zone macrophages. Eur. J. Immunol.,27: 2626-2633, 1997. (bisphosphonate-liposome macrophage depletion method).
Ludewig, B., Barchiesi, F., Pericin, M., Zinkernagel, R.M., Hengartner, H. Schwendener, R.A. In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediated protective antiviral and antitumor immunity. Vaccine 19: 23-32 (2000).
Roscic-Mrkic, B., Schwendener, R.A., Odermatt, B., Zuniga, A., Pavlovic, J., Billeter, M.A., Cattaneo, R. The role of macrophages in measles virus infection of genetically modified mice. J.Virol. 75: 3343-3351, 2001. (bisphosphonate-liposome macrophage depletion method).
Schwendener, R.A., Friedl, K., Depenbrock, H., Schott, H., Hanauske, A.-R. In vitro activity of liposomal N4-octadecyl-1-b-D-arabinofuranosyl-cytosine (NOAC), a new lipophilic derivative of 1-b-D-arabinofuranocylcytosine on biopsized clonogenic human tumour cells and haematopoietic precursor cells. Invest. New Drugs 19: 203-210, 2001.
Seiler, P., Schwendener, R., Bandermann, S., Brinkmann, V., Grode, L., Kaufmann, S. H.E., and Aichele, P. Limited mycobacterial infection of the liver as a consequence of its micro anatomical structure causing growth restriction of bacteria to professional phagocytes. Infect. Immun. 69: 7922-7926, 2001. (bisphosphonate-liposome macrophage depletion method).
Marty, C., Ballmer-Hofer, K., Neri, D., Klemenz, R., Schott, H., Schwendener, R.A. Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes. Br. J. Cancer 87: 106-112, 2002.
Madjidpour, C., Jewell, U.R., Kneller, S., Ziegler, U., Schwendener, R.A., Booy, Ch., Kläusli, L., Pasch, T., Schimmer, R.C. and Beck-Schimmer, B. Decreased alveolar oxygen induces lung inflammation. Am. J. Physiol. Lung Cell. Mol. Physiol. 284: L360-L367, 2003. (bisphosphonate-liposome macrophage depletion method).