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 potency of various anionic liposomal formulations in a serum-supplemented growth 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, which lacks the LDL receptor. Cellular association of encapsulated methotrexate and fluorescein labeled phosphatidylethanolamine in the lipid bilayer was measured. Potency of two liposome-dependent drugs (N-phosphonacetyl-L-aspartic acid and fluoroorotic acid) was also measured by growth inhibition. Association of ePG liposomal aqueous contents with cells grown in serum-supplemented 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 corresponding increase in potency of liposome-dependent drugs. The serum-dependent association of fluid, anionic (ePG) liposomes with cells expressing the LDL receptor is caused by an interaction of ePG liposomes with LDL. The failure of this association to increase drug delivery seems to be caused by the downregulation of LDL receptor expression when cells are continuously exposed to LDL.