The effect of DSPE-PEG2000, cholesterol and drug incorporated in bilayer on the formation of discoidal micelles

In cholesterol/DSPE-PEG 2000 /DPPC systems, nano-disks could evolve between liposomes and spherical micelles in a certain range of PEG-lipids. How cholesterol or drug influences this evolution and what about the properties of discoidal micelles as drug carrier are still not clear. Aiming at this, nanocarriers with different contents of cholesterol and DSPE-PEG 2000 were prepared by thin-film-hydration method. Firstly, the bilayer fluidity of nanocarriers was investigated and proved to decrease with the increase of cholesterol, and the cooperative degree between phospholipids was also related to cholesterol content in an order of 30 > 40 > 15 > 0 mol%. Then three different levels of cholesterol were chosen to study its effect on DSPE-PEG 2000 limit used to form discoidal micelles. For transition from liposomes to disks, the limit of DSPE-PEG 2000 employed is above 0.5 mol% at 0 mol% cholesterol, above 15 mol% at 30 mol% cholesterol and above 5 mol% at 40 mol% cholesterol observed from TEM images, indicating that nanocarriers with 30 mol% cholesterol formed discoidal micelles most difficultly due to the strongest interaction between phospholipids. However, membrane fluidity seems to have little responsibility for the different morphologies. And imatinib (IM) could promote the formation of discoidal micelles, resulting from the interaction between IM and polar headgroups of phospholipid demonstrated by DSC . The relative reduction of entrapment efficiency for three agents with different dissolving properties showed that lipophilic drugs were the most suitable drug that could be loaded into discoidal micelles. In addition, the discoidal micelle formulations tested could readily change to other morphologies after 80 days' storage. In conclusion, both the cholesterol content and IM could affect the formation of discoidal micelles by probably influencing the interaction between phospholipids, also the discoidal structure was not stable enough and only suitable for lipophilic drug loading. We hope this study could help to design the formula and choose the proper drugs that may retain the discoidal morphology.