Interaction of a lipid-membrane destabilizing enzyme with PEG-liposomes.
Polymer grafted PEG-liposomes have come into use as drug-delivery systems with improved therapeutic profiles. However, very little is known about the morphological instability of PEG-liposomes due to enzymatic degradation. To gain further insight into the effect of PEG lipopolymer-concentration on the catalytic activity of a liposome-degrading enzyme, phospholipase A2 (PLA2)-catalyzed phospholipid hydrolysis of PEG-liposomes has been investigated. The temperature dependence of the PLA2 lag-time, denoting the time required before a sudden increase in enzymatic activity takes place, has been determined for submicellar amounts of dipalmitoylphosphatidylethanolaminyl-poly-(ethylene glycol) (DPPE-PEG2000) incorporated into unilamellar dipalmitoylphosphatidylcholine (DPPC)-liposomes. The measurements demonstrate a significant reduction in the lag-time over broad temperature ranges. The results suggest that a close relationship exists between PLA2 catalyzed lipid hydrolysis and lipid-membrane composition, which moreover is of major importance for the overall morphological stability and the release of encapsulated material from the polymer-grafted PEG-liposomes.
Jørgensen
K
K
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark. jorgense@kemi.dtu.dk
Kiebler
T
T
Hylander
I
I
Vermehren
C
C
D016503:Drug Delivery Systems; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011092:Polyethylene Glycols / Q000378:metabolism*; D013696:Temperature
D008081:Liposomes; D010714:Phosphatidylethanolamines; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D011092:Polyethylene Glycols; D010741:Phospholipases A; D054467:Phospholipases A2