Abstract
OBJECTIVE: This work evaluates the
potential of lipid-coated microbubbles (LCM) as a delivery vehicle for
lipid-soluble antineoplastic agents. We have shown, in rats, the
selective affinity of intravenously administered LCM for tumor cells.
They are internalized by the tumor cells both in vitro and in vivo. The
specificity of LCM for tumors and subsequent incorporation into the
cytoplasm could significantly reduce the systemic effects of an agent
incorporated into the bubbles, such as Taxol.
METHODS: The in vitro
methods were as follows. C6 cells were treated with Taxol-LCM (6 ug/ml),
Taxol-Cremophore (6 ug/ml), or LCM alone for 8 or 24 hours. Cell death
was determined by staining the cells with nuclear staining.
Abnormalities of microtubule structures were ascertained by confocal
microscopy. The in vivo methods were as follows. Two rat tumor models
(C6 and 9L) were used. Rats were treated with single bolus injections
or with repetitive (two or three) treatment courses, with respective
control animals. Each course consisted of one daily tail vein injection
for 5 consecutive days and then 2 days of rest.
RESULTS: When
compared with either a saline control group or a group receiving Taxol
in an oil vehicle, Taxol-LCM reduced tumor progression in Fisher-344
rats inoculated with 9L glioma. The most profound effect was observed
with rats treated with three treatment cycles (five daily
injections/cycle) separated by two rest periods (2 d/period).
CONCLUSION:
Both in vitro and in vivo data indicate that Taxol can be incorporated
into LCM, can be delivered to the tumor site, and can exert a measurable
antitumor biological effect.