Transfer of lipophilic drugs between liposomal membranes by using the ion-exchange micro-column technique and the fluorescence dequenching effect

The parenteral and oral administration of lipophilic drugs is often problematic because of their low water solubility. Liposomes are composed of relatively biocompatible and biodegradable materials consisting of an aqueous volume entrapped by one or more bilayers of natural and/or synthetic lipids. Therefore, drug-containing liposomal formulations are considered as one of the most promising nano-particle based technologies for drug delivery to solid tumours, sites of inflammation and skin permeation. An understanding of the mechanisms involved in the transport of drug from tissues to plasma, and its subsequent transfer to the liver for degradation, is of great importance. It is necessary to develop an in vitro model to mimic the in vivo transfer of the drug in order to explain the transport mechanisms involved. The present study aims to investigate the factors which influence the transfer of lipophilic drugs and to look for the mechanisms during the drug transfer process. Two in vitro models have been selected in the investigation. The first model is based on the ion-exchange micro-columns. The transfer kinetics of three compounds, paclitaxel, cholesterol and cholesteryl-oleoyl-ether has been investigated. The drugs are transferred from positively (or negatively) charged, unilamellar DOPC (1,2-Dioleoyl-sn-Glycero-3-phosphocholine) donor vesicles to 5 times excess of neutral POPC (1-Palmitoyl-2-oleoyl-snglycero-3-phosphocholine) acceptor vesicles. The vesicles were incubated in the absence of protein and were stable from fusion over the course of the experiment. At different periods of time, donor and acceptor vesicles are separated by passing throughout a column filled with CM Sepharose FF (or DEAE-Sepharose). The transfer of the drugs is then measured by HPLC or LSC.


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