LDL induced association of anionic liposomes with cells and delivery of contents as shown by the increase in potency of liposome dependent drugs

Purpose. To establish whether anionic liposomes interact with the low-densi ty lipoprotein (LDL) receptor, to determine the role of lipoproteins in thi s interaction, and whether the association causes functional delivery of en capsulated drugs. Methods, The cell lines used were CV1-P and CHO wild type, both of which ex press the LDL receptor, and CHOldlA7, which lacks the LDL receptor. Cellula r association of encapsulated methotrexate and fluorescein. labeled phospha tidylethanolamine in the lipid bilayer, was measured. Potency of three lipo some dependent drugs (N-phosphonacetyl-L-aspartic acid. fluoroorotic acid, and methotrexate-gamma -aspartate) was also measured by growth inhibition. Results, Association of liposomes containing at least 75 mol egg phosphatid ylglycerol (ePG)/100 mol phospholipid with cells grown in defined medium su pplemented with 1.0 mg/ml LDL was up to 30-fold higher with CV1-P or CHO wi ld type cells than with CHOldlA7, and 5-fold higher than association in def ined medium lacking LDL. The addition of LDL did not yield any elevation of cellular association of distearoylphosphatidylglycerol liposomes. Increase d association was paralleled by a corresponding increase in potency of all three liposome dependent drugs tested. Conclusions. ePG liposomes interact with the LDL receptor in an LDL-depende nt fashion, and the interaction results in the delivery of contents to cell s.