Enzymatic degradation of polymer covered SOPC-liposomes in relation to drug delivery.
Polyethylenoxide (PEG) covered liposomes are used as lipid-based drug-delivery systems. In comparison to conventional liposomes the polymer-covered liposomes display a long circulation half-life in the blood stream. We investigate the influence of polyethyleneoxide-distearoylphosphatidylethanolamine (DSPE-PEG750) lipopolymer concentration on phospholipase A2 (PLA2) catalyzed hydrolysis of liposomes composed of stearoyloleoylphosphatidylcholine (SOPC). The characteristic PLA2 lag-time was determined by fluorescence and the degree of lipid hydrolysis was followed by HPLC analysis. Particle size and zeta-potential were measured as a function of DSPE-PEG750 lipopolymer concentration. A significant decrease in the lag-time, and hence an increase in enzyme activity, was observed with increasing concentrations of the anionic DSPE-PEG750 lipopolymer lipids. The observed decrease in lag-time might be related to changes in the surface potential and the PLA2 lipid membrane affinity.
Davidsen
J
J
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen O.
Vermehren
C
C
Frøkjaer
S
S
Mouritsen
O G
OG
Jørgensen
K
K
D016503:Drug Delivery Systems; D004586:Electrophoresis; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008081:Liposomes; D008564:Membrane Potentials; D010316:Particle Size; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010741:Phospholipases A / Q000737:chemistry* / Q000378:metabolism; D054467:Phospholipases A2; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties
D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; C027891:1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine; D010741:Phospholipases A; D054467:Phospholipases A2