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Visualization of bioavailable liposomal
doxorubicin using a non-perturbing confocal imaging technique
R. Krishna*, G. Ghiu and L.D. Mayer
Department of Advanced Therapeutics, BC Cancer Agency, Vancouver,
Canada and
Faculty of Pharmaceutical Sciences, University of British Columbia,
Vancouver, Canada
*Present address: Department of Metabolism and Pharmacokinetics,
Bristol-Myers Squibb Co., Princeton, NJ, USA
Offprint requests to: Dr.
L. Mayer, Department of Advanced Therapeutics, BC Cancer Agency,
Vancouver, BC, V5Z 4E6, Canada. Fax: (604) 877 6011.
Summary. Commonly employed tissue processing techniques
can significantly alter tissue drug distribution patterns for
liposomal encapsulated drugs by virtue of drug leakage via loss
of membrane integrity. We report here a method that has been developed
to determine the fluorescence of bioavailable doxorubicin (DOX)
in tissues after administration of liposomal DOX formulations.
A non-perturbing confocal fluorescence microscopy (CFM) technique
with image processing analysis was used with unprocessed fresh
tissues. This method takes advantage of the fact that considerable
quenching occurs when DOX is within liposomes, leading to the
selective visualization of the fluorescence due to DOX released
from liposomes. We demonstrate that fresh tissue confocal imaging
can be applied to provide detailed drug distribution information
with improved accuracy and is a superior method for analyzing
tissue distribution of liposome entrapped fluorescent agents.
Histol. Histopathol. 16, 693-699 (2001)
Key words: Tissue localization, Imaging, Liposomes
DOI: 10.14670/HH-16.693
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