Delivery of Lipophilic Drugs Using Lipoproteins

Low density lipoproteins (LDLs) and high density lipoproteins (HDLs), are spherical classes of particles 7 to 25 nm in diameter with oily, nonaqueous cores. Extensive studies have been performed throughout the years with respect to the structure, metabolism, and molecular biology of lipoproteins. Recently lipoproteins, most notably LDL, have been examined experimentally as drug-delivery vehicles. Advantages of lipoproteins as drug carriers include: (1) their being natural components able to survive in plasma and tissue fluids for significant time periods, (2) the small particle size, which allows diffusion from vascular to extravascular compartments, (3) their interaction via receptor-mediated endocytosis enabling intracellular uptake of drug, and (4) the oily core, which provides a domain for lipophilic drugs and prodrugs. Disadvantages of lipoproteins as drug carriers include their complex and unstable nature, a general lack of targeting since receptors for some lipoproteins reside on numerous tissues, and potential drug cytotoxicity to normal tissues. In the present studies, the preparation, composition, and stability of lipoprotein-drug complexes are described. Interactions of these complexes with cells in vitro were performed to establish how the modified lipoprotein particles and drugs became cell associated and what biological effects occurred on the target cells.