TY - JOUR
T1 - Validation of the reconstituted high-density lipoprotein (rHDL) drug delivery platform using dilauryl fluorescein (DLF)
AU - McConathy, Walter J.
AU - Paranjape, Sulabha
AU - Mooberry, Linda
AU - Buttreddy, Sabitha
AU - Nair, Maya
AU - Lacko, Andras G.
N1 - Funding Information:
This study was supported in part by the Department of Defense Congressionally Directed Breast Cancer Research Program (BC5286) and by the James R. Winterringer Cancer Research Fund (Cowtown Cruisers for the Cure). The ldl A7 and ldl A7 [mSR-BI] cell lines were kindly provided by Dr. Monty Krieger at the Massachusetts Institute of Technology.
PY - 2011/4
Y1 - 2011/4
N2 - 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. These studies show that DLF can be incorporated into rHDL and redistributed in the plasma compartment. In addition, these studies demonstrated an enhanced uptake and hydrolysis of DLF from rHDL by cells that overexpress the SR-B1 receptor, suggesting the involvement of a receptor mediated mechanism. The incorporation of DLF into the rHDL nanoparticles appear to protect against hydrolysis in the systemic circulation based on the lower rate of rHDL/DLF hydrolysis compared with the free DLF during incubation with human plasma. DLF may thus be used as a probe to track the movement and metabolism of HDL core constituents, including cancer chemotherapeutic agents.
AB - 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. These studies show that DLF can be incorporated into rHDL and redistributed in the plasma compartment. In addition, these studies demonstrated an enhanced uptake and hydrolysis of DLF from rHDL by cells that overexpress the SR-B1 receptor, suggesting the involvement of a receptor mediated mechanism. The incorporation of DLF into the rHDL nanoparticles appear to protect against hydrolysis in the systemic circulation based on the lower rate of rHDL/DLF hydrolysis compared with the free DLF during incubation with human plasma. DLF may thus be used as a probe to track the movement and metabolism of HDL core constituents, including cancer chemotherapeutic agents.
KW - Chemotherapy
KW - Controlled release
KW - Drug delivery
KW - Protective transport
KW - Receptor mediated uptake
KW - Reconstituted HDL
UR - http://www.scopus.com/inward/record.url?scp=84861311694&partnerID=8YFLogxK
U2 - 10.1007/s13346-010-0012-0
DO - 10.1007/s13346-010-0012-0
M3 - Article
AN - SCOPUS:84861311694
SN - 2190-393X
VL - 1
SP - 113
EP - 120
JO - Drug Delivery and Translational Research
JF - Drug Delivery and Translational Research
IS - 2
ER -