PHYSICOCHEMICAL CHARACTERIZATION OF PROTEIN-FREE LOW-DENSITY-LIPOPROTEIN MODELS AND INFLUENCE OF DRUG LOADING

Purpose. Drug free and drug loaded protein-free low density lipoprotei n (LDL) models consisting mainly of phospholipids, cholesterol, choles terol esters, and triglycerides in ratios found for physiological LDL have been prepared. Their physicochemical characteristics were compare d with those of physiological LDL. Methods. Different characterization methods were used: photon correlation spectroscopy, transmission elec tron microscopy, X-ray solution scattering, and H-1 nuclear magnetic r esonance spectroscopy (NMR). Results. Particle sizes are highly depend ent on the preparation method and in particular on the homogenization conditions. Electron microscopy indicates that the size distributions of model systems are much broader than those of physiological LDL. The X-ray solution scattering patterns of the model systems display a tem perature dependent maximum near 3.8 nn similar to that found in the pa tterns of physiological LDL. NMR indicates a comparable mobility of th e lipid molecules in model particles and in physiological LDL. The inf luence of drug loading is similar to that found earlier for physiologi cal LDL. In particular, the incorporation of the anticancer drug WE 42 91 seems to have a fluidizing effect on the lipids in the core region of the particles. Conclusions. The preparation method of LDL model sys tems is of crucial importance as only the solvent evaporation method y ielded systems in the size range of physiological LDL with acceptable high lipid concentrations. The fluidizing influence of temperature and drug incorporation (WE 4291) may be a disadvantage in drug targeting.