High Density Lipoprotein Complexes as Delivery Vehicles for Breast Cancer Chemotherapy
Abstract
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 rHDL/Taxol 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 (r2=O.89; p<O.04). Finally, we have found that the uptake of paclitaxel from an rHDL/paclitaxel 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 rHDL/drug complexes is facilitated by a receptor-mediated mechanism and thus should provide an improved formulation for targeted chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA426184
Entities
People
- Andras G. Lacko
Organizations
- University of North Texas Health Science Center