The effect of
liposome composition on
drug delivery to
tumors and therapeutic efficacy of
liposome-encapsulated
anthracyclines was investigated in two murine
tumor models: an ascitic
tumor (J6456
lymphoma) and a solid
carcinoma (M-109). Longevity in circulation correlated positively with high
drug levels in the extracellular (ascitic)
tumor fluid and with delayed peak
tumor levels. Using
polyethylene-glycol(PEG)-coated
liposomes,
liposome stability (
drug retention) was found to be an important determinant of therapeutic efficacy, as indicated by the superior survival conferred by high Tm
phosphatidylcholines (hydrogenated, dipalmitoyl) over low Tm (egg
phosphatidyl-choline). Replacing PEG with another negatively-charged surface headgroup (
phosphatidyl-glycerol,
phosphatidyl-inositol) resulted in relatively shorter longevity in circulation of the
liposome-associated
drug, but no detectable differences in anti-
tumor efficacy. When neither the surface charged headgroup nor the PEG coating are present, the resulting
drug formulation was significantly less effective than PEG and
phosphatidylinositol-based formulations in both
tumor models. In conclusion, longevity in circulation, as obtained with PEG coating, tends to improve the therapeutic efficacy of
liposome-encapsulated
anthracyclines. The current therapeutic models were however unable to detect differences between the therapeutic activity of PEG and other
liposome formulations with relatively small differences in circulation longevity.