Purpose. To examine the internalization of liposomes containing variou
s phospholipids by human retinal pigment epithelial (RPE) cells in cul
ture. The internalization was compared to that exhibited by macrophage
s and fibroblast cells. Methods. The uptake into cells was monitored b
y using a nondegradable, radioactive cholesterol-hexadecyl ether deriv
ative and a pH-sensitive, water-soluble fluorescent dye. Variables tes
ted to determine their effect on uptake included time, phospholipid co
ncentration, the presence or absence of serum in medium and the presen
ce or absence of cholesterol in the liposome bilayer. The most avidly
ingested liposome was tested to determine its ability to deliver a lip
osome-dependent drug. Results. Liposome uptake was time and concentrat
ion dependent. Uptake for RPE was maximal in serum-free media, while t
he opposite was true for the other cells tested. Cell survival followi
ng exposure to fluoroorotic acid-containing liposomes correlated with
the radioactive cholesterol-hexadecyl ether and fluorescent dye uptake
data. Conclusions. No single liposome carrier or set of conditions te
sted appeared to be optimum for the delivery of a cytotoxic agent to t
hese three cell types. This bears consideration when designing strateg
ies for the prevention and treatment of intraocular proliferative dise
ases such as proliferative vitreoretinopathy (PVR).