Crystallization behavior of supercooled smectic cholesteryl myristate nanoparticles containing phospholipids as stabilizers

Supercooled smectic nanoparticles based on physiological cholesterol esters are under investigation as a potential novel carrier system for lipophilic drugs. The present study investigates the very complex crystallization behavior of such nanoparticles stabilized with the aid of phospholipids. Phospholipid and phospholipid/bile salt stabilized cholesteryl myristate dispersions were prepared by high-pressure melt homogenization and characterized by particle size measurements, differential scanning calorimetry, X-ray diffraction and electron microscopy. To obtain fractions with very small smectic nanoparticles, selected dispersions were ultracentrifuged. A mixture of cholesteryl myristate and the phospholipid used for the stabilization of the dispersions was also investigated by light microscopy. The nanoparticles usually display a bimodal crystallization event which depends on the thermal treatment and cannot be attributed to crystalline polymorphism. The ratio of the particle fractions crystallizing in the two successive steps strongly depends on the particle size of the dispersions. The presence of larger particles leads to an increased fraction crystallizing at higher temperature and a higher recrystallization tendency upon storage. The observed peculiarities of the crystallization behavior seem to be mainly caused by the presence of particles with different shapes (cylindrical and spherical) as observed in electron microscopy. Alterations in the composition of the nanoparticles may also play a role.