High Density Lipoprotein Complexes as Delivery Vehicles for Breast Cancer
Final rept. 1 May 2001-30 Apr 2003
UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER FORT WORTH TX
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Reconstituted high density lipoprotein rHDL particles have been developed to incorporate water insoluble drugs to serve as drug delivery agents. Specifically, we have prepared taxol TX containing rHDL particles that am stable on rechromatography and preparative ultracentrifugation as no losses of TX from the complexes were seen during these studies. The rHDLTX complexes were as toxic to breast cancer cells as the commercial cremophortaxol preparations. Taxol was avidly taken up by cancer cells from the rHDLTX complexes, apparently by an SRB1 type receptor mediated mechanism. The uptake of core components from the rHDL complexes by a receptor mediated mechanism is supported by the observed expression of the SRB1 type receptors demonstrated by immunoblotting and by competition studies. Cancer cells were shown to exhibit considerably higher SRB1 receptor expression than fibroblasts, suggesting that the rHDL drug delivery system may be specifically targeting malignant cells.
- Medicine and Medical Research