High Density Lipoprotein Complexes as Delivery Vehicles for Breast Cancer Chemotherapy
Final addendum 1 May 2003-30 Apr 2004
UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER FORT WORTH TX
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A platform technology has been established, based on reconstituted high density lipoprotein rHDL nanoparticles, to facilitate the delivery of intravenously administered drugs including cancer chemotherapeutic agents. We have prepared rHDLTaxol complexes with a consistent composition and molecular weight that exhibited exceptional stability upon repeated gel chromatography and ultracentrifugation. Studies in mice led to the observation that about ten times as much HDL encapsulated Taxol remained in the circulation, 1 hr post injection, compared to free Taxol. We have examined a number of cancer cell lines for their ability to incorporate cholesterol esters and Taxol from rHDL complexes. The delivery of cholesteryl esters and paclitaxel was nearly as efficient to cancer cells as it was to a normal control ovarian granulosa cells. We also showed that the uptake efficiency of cholesteryl esters and pacliataxel by cancer cells were closely correlated r2O.89 pO.04. Finally, we have found that the uptake of paclitaxel from an rHDLpaclitaxel formulation by cancer cells is inhibited by HDL3 in a concentration dependent manner. These findings strongly suggest that the uptake of chemotherapeutic agents from the rHDLdrug complexes is facilitated by a receptor-mediated mechanism and thus should provide an improved formulation for targeted chemotherapy.
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