CHARACTERIZATION OF NATIVE AND DRUG-LOADED HUMAN LOW-DENSITY LIPOPROTEINS

Low-density lipoproteins (LDLs), the physiological vehicles for lipids , are potentially useful drug delivery devices for (hydrophobic) drugs . The physicochemical characteristics of LDL loaded with the adriamyci n derivative AD 32 or the N-mustard derivative WE 4298 were compared t o that of native and reconstituted tot at different temperatures. X-ra y solution scattering indicates that loading with AD 32 has no detecta ble effect on the particle structure at room temperature, in contrast to WE 4291. According to F-19 NMR data, AD 32 molecules are located in two distinct chemical environments with restricted motional freedom o f the CF3 groups in samples stored as lyophilisates. H-1 NMR signals f rom AD 32 were not observed, while those from WE 4291 could be disting uished from those of LDL constituents. WE 4291 molecules are in an env ironment with a higher motional freedom than AD 32 molecules. H-1 NMR data suggest a higher fluidity of the core components for the WB-loade d LDLs compared to the other LDL preparations. While the motional free dom of the phospholipid head groups seems to be temperature independen t, there is an increase in the mobility of the lipid components in the core region of the LDL particles with temperature.