LDL-induced association of anionic liposomes with cells and delivery of contents - II. Interaction of liposomes with cells in serum-containing medium

In the present study we have investigated cell binding and drug delivery po tency of various anionic liposomal formulations in a serum-supplemented gro wth medium, in order to understand the role of the LDL receptor in targeted drug delivery mediated by anionic liposomes. The cell lines used were CV1- P and CHO wild type, which both express the LDL receptor, and CHOldlA7, whi ch lacks the LDL receptor. Cellular association of encapsulated methotrexat e and fluorescein labeled phosphatidylethanolamine in the lipid bilayer was measured. Potency of two liposome-dependent drugs (N-phosphonacetyl-L-aspa rtic acid and fluoroorotic acid) was also measured by growth inhibition. As sociation of ePG liposomal aqueous contents with cells grown in serum-suppl emented growth medium was up to 30-fold higher with CV1-P or CHO wild type cells than with CHOldlA7. Increased association was not paralleled by a cor responding increase in potency of liposome-dependent drugs. The serum-depen dent association of fluid, anionic (ePG) liposomes with cells expressing th e LDL receptor is caused by an interaction of ePG liposomes with LDL. The f ailure of this association to increase drug delivery seems to be caused by the downregulation of LDL receptor expression when cells are continuously e xposed to LDL. (C) 2001 Elsevier Science B.V. All rights reserved.