Liposome uptake by human retinal pigment epithelial cells in culture.
OBJECTIVE
To examine the internalization of liposomes containing various phospholipids by human retinal pigment epithelial (RPE) cells in culture. The internalization was compared to that exhibited by macrophages and fibroblast cells.


METHODS
The uptake into cells was monitored by using a non-degradable, radioactive cholesterol-hexadecyl ether derivative and a pH-sensitive, water-soluble fluorescent dye. Variables tested to determine their effect on uptake included time, phospholipid concentration, the presence or absence of serum in medium and the presence or absence of cholesterol in the liposome bilayer. The most avidly ingested liposome was tested to determine its ability to deliver a liposome-dependent drug.


RESULTS
Liposome uptake was time and concentration dependent. Uptake for RPE was maximal in serum-free media, while the opposite was true for the other cells tested. Cell survival following 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 tested appeared to be optimum for the delivery of a cytotoxic agent to these three cell types. This bears consideration when designing strategies for the prevention and treatment of intraocular proliferative diseases such as proliferative vitreoretinopathy (PVR).
Niesman
M R
MR
Arkansas Center for Eye Research, Little Rock, USA. mniesman@acer.uams.edu
Peyman
G A
GA
Miceli
M V
MV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001190:Arylsulfonates / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D004396:Coloring Agents; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009963:Orotic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013778:Tetrazolium Salts; D013844:Thiazoles
D001190:Arylsulfonates; D004396:Coloring Agents; D005456:Fluorescent Dyes; D008081:Liposomes; D010743:Phospholipids; D013778:Tetrazolium Salts; D013844:Thiazoles; D009963:Orotic Acid; C001242:5-fluoroorotic acid; C022616:thiazolyl blue; C005047:pyranine