Abstract
The activity of doxorubicin hydrochloride in preclinical tumor models is markedly improved by encapsulation in pegylated liposomes (DOXIL, CAELYX). To understand this response in better detail, spatial and temporal drug distribution in frozen tumor sections was observed with confocal laser scanning (CLS) microscopy. Tumor tissue absorption and distribution phases were markedly altered by pegylated liposome encapsulation. The resultant tumor tissue area under the curve was increased at least several fold over an equivalent dose of free drug. The majority of visible fluorescence was in the nuclear compartment; encapsulated drug apparently leaves liposomes in the interstitial spaces within minutes and appears in the nucleus. Pilot experiments suggest that drug and lipid uncouple at an extracellular location. The increased nuclear exposure to drug is likely responsible for the enhanced therapeutic effect of encapsulation in pegylated liposomes.
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