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Critical Reviews™ in Therapeutic Drug Carrier Systems
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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v18.i2.10
32 pages

Liposomal Formulations of Cyclosporin A: A Biophysical Approach to Pharmacokinetics and Pharmacodynamics

A. Fahr
Department of Pharmaceutical Technology and Biopharmacy, University of Marburg, Ketzerbach 63, 35032 Marburg, Germany
J. Seelig
Department of Biophysical Chemistry, Biocenter of the University of Basel, Klin-gelbergstrabe 70, CH-4056 Basel, Switzerland

ABSTRACT

There are about 20 publications about liposomal formulations of Cyclosporin A (CyA) in the pharmaceutical and preclinical literature. Liposomal formulations were developed in order to reduce the nephrotoxicity of CyA and to increase pharmacological effects. However, conflicting results have been published as to the therapeutic properties of these formulations. This is also true for the change in pharmacokinetics and organ distribution of the liposomally encapsulated CyA as compared to conventionally formulated CyA. Using biophysical methods, it could be shown that CyA is not tightly entrapped in liposomal membranes, despite its high lipophilicity. CyA shows retardation only at high lipid concentrations in blood, following a massive injection of liposomes.This effect may diminish nephrotoxicity, as could be demonstrated by in vitro studies using a model tubule system. The results of these studies can be used to predict the formulation behavior in vivo and to optimize liposomal formulations. When applied in an early phase of the drug formulation process, these types of biophysical experiments can also help minimize animal experiments. However, these basic interaction studies cannot cover all physiological, pharmacological, and toxic effects in animals and humans.


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