Nanosized bilayer disks: Attractive model membranes for drug partition studies

Abstract

Stable nanosized bilayer disks were prepared from either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, or lipid mixtures with a composition reflecting that of the porcine brush border membrane. Two different polyethylene glycol (PEG)-grafted lipids, the negatively charged 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-5000] (DSPE-PEG(5000)) and the neutral N-palmitoyl-sphingosine-1-[succinyl (methoxy (polyethylene glycol) 5000] (Ceramide-PEG(5000)), were used to stabilize the disks. The disks were employed as model membranes in drug partition studies based on a fast chromatography method. Results show that the lipid composition, as well as the choice of PEG-lipid, have an important influence on the partition behavior of charged drugs. Comparative studies using multilamellar liposomes indicate that bilayer disks have the potential to generate more accurate partition data than do liposomes. Further, initial investigations using bacteriorhodopsin suggest that membrane proteins can be reconstituted into the bilayer disks. This fact further strengthens the potential of the bilayer disk as an attractive model membrane.

Influence of preparation path on the formation of discs and threadlike micelles in DSPE-PEG2000/lipid systems

“…In previous studies we have shown that the composition of the discs can be varied and e.g. tailored to reflect that of a biological membrane [14,15]. Further, the size of the discs can be altered by changing the PEG-lipid content [13].…”

“…The discs have e.g. been utilized as a model membranes in drug/membrane partitioning studies [13][14][15]. Results of these studies suggest that the discs, due to their stable and open structure, in many cases are superior to liposomes as model membranes.…”

Immobilized lipodisks as model membranes in high-throughput HPLC-MS analysis

“…PEG-stabilized bilayer disks, henceforth referred to as lipodisks, have emerged as an interesting alterative to liposomes for the use as model membranes in interaction studies (16)(17)(18)(19)(20). The lipodisks are flat circular lipid aggregates consisting of a lipid bilayer surrounded by a highly curved rim (see schematic picture in Figure 1).…”

“…The size of the disks can be varied by alteration of the PEG-lipid content (17,22). Furthermore, the lipid composition can be adjusted to closely mimic that of biological cell membranes (16,18). Similar to the case with liposomes, membrane spanning, as well as peripheral, membrane proteins can be incorporated into the lipodisks (16,23).…”

“…Furthermore, the lipid composition can be adjusted to closely mimic that of biological cell membranes (16,18). Similar to the case with liposomes, membrane spanning, as well as peripheral, membrane proteins can be incorporated into the lipodisks (16,23). However, in contrast to the case with liposomes, the open structure of the disks ensures that both lipid bilayer leaflets are readily available for interaction with analytes present in the bulk aqueous phase.…”