Validation of the reconstituted high-density lipoprotein (rHDL) drug delivery platform using dilauryl fluorescein (DLF).

Dilauryl fluorescein (DLF) is a lipid soluble molecule that becomes fluorescent when lauric acid is removed by hydrolysis The purpose of these studies was to evaluate DLF as a potential probe for the function of reconstituted high-density lipoproteins (rHDL) as hydrophobic drug transport vehicles. The DLF containing rHDL nanoparticles were characterized regarding their physical/chemical properties, including molecular diameter, molecular weight, chemical composition, and buoyant density. We investigated the uptake of DLF from rHDL in cells that overexpress the scavenger receptor (SR-B1), known to facilitate the selective cellular uptake of cholesteryl esters from HDL.

Receptor mediated uptake of paclitaxel from a synthetic high density lipoprotein nanocarrier.

The purpose of these studies was to determine the mechanism(s) whereby paclitaxel (PTX), is taken up by cancer cells, once encapsulated into synthetic/reconstituted high density lipoprotein (rHDL). The uptake of PTX was found to be facilitated by the scavenger receptor type B-1 (SR-B1) when drug-loaded rHDL particles were incubated with cells that express the SRB1 receptor. Studies with double-labeled, PTX containing rHDL nanoparticles showed that prostate cancer (PC-3) cells incorporated PTX primarily via a selective (SR-B1 type) uptake mechanism.

Evaluation of synthetic/reconstituted high-density lipoproteins as delivery vehicles for paclitaxel.

Reconstituted (synthetic) high-density lipoprotein particles carrying paclitaxel (rHDL/PTX) were prepared with substantially higher PTX content than reported earlier. The rHDL/PTX complexes seemed to be primarily spherical nanoparticles when examined via electron microscopy, with a constant composition, molecular weight and exceptional stability even after ultracentrifugation and storage for up to 6 months. The rHDL/PTX nanoparticles had superior cytotoxicity against several cancer cell lines (MCF7, DU145, OV1063 and OVCAR-3), the half maximal inhibitory concentration (IC50) having been found to be 5-20 times lower than that of the free drug.

Trojan horse meets magic bullet to spawn a novel, highly effective drug delivery model.

Because of their physicochemical properties and the selective receptor-mediated uptake of their core components, reconstituted high-density lipoproteins have unique advantages over conventional formulations to serve as targeted drug delivery agents.

High density lipoprotein complexes as delivery vehicles for anticancer drugs.

Materials And Methods: Recombinant high density lipoprotein (rHDL) particles were prepared with defined composition (phosphatidylcholine, apolipoprotein A-1, cholesterol and cholesteryl esters) and a molecular weight of approximately 187,000 kdaltons. Three molecules of taxol per rHDL particle were incorporated into these rHDL complexes.

Results: Cholesteryl ester and taxol (HDL core components,) were taken up efficiently by several cancer cell lines compared to transformed normal ovarian cells (HGL5) used as the control.