Synergistic effect of phospholipid-based liposomes and propylthiouracil on U-937 cell growth.
Scientific evidence indicates that exogenous phospholipids in the form of liposomes can affect cell growth. Effects of liposomes on cell growth depend on several factors including composition of liposomes, lipid concentration, and type of cells studied. Because phagocytic cells such as monocytes and macrophages are natural targets of liposomes, intracellular delivery of drugs to modulate cellular activity of these cells is of interest. We explored the effects of phospholipid-based liposomes composed of soy bean phosphatidylcholine (PC) as the main lipid component on U-937 cell growth. Effects of charge-imposing lipids and cholesterol were also studied. In addition, we investigated whether phospholipid-based liposomes would exert any interaction on cell growth with propylthiouracil, a drug with known antiproliferative activity. We found that PC in the form of extruded liposomes had intrinsic antiproliferative activity on U-937 cells at concentrations of 200 microM and up without any appreciable cytotoxicity. Phosphatidylserine and phosphatidylglycerol, but not dicetlylphosphate, at 10 mol% increased growth retardation activity of PC liposomes. Cholesterol at 30 mol% did not have any effect on cell growth, except for liposomes composed of PC and phosphatidylserine, where growth retardation was negated in the presence of cholesterol. Synergistic effect on cell growth was seen with certain liposome compositions when 5.5 microg/mL of propylthiouracil was coincubated. The results of this study suggest that the effects of exogenous lipids on cell growth should be taken into consideration when PC-based liposomes are to be used as drug delivery systems, especially when the targets are cells with phagocytic activity.
Puapermpoonsiri
Utsana
U
Department of Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Lipipun
Vimolmas
V
Vardhanabhuti
Nontima
N
D000818:Animals; D000963:Antimetabolites / Q000737:chemistry; D002417:Cattle; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D016503:Drug Delivery Systems; D004357:Drug Synergism; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011441:Propylthiouracil / Q000737:chemistry*
D000963:Antimetabolites; D008081:Liposomes; D010743:Phospholipids; D011441:Propylthiouracil; D002784:Cholesterol