Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles

Abstract

Despite the obvious similarities between colloidal lipid suspensions (solid lipid nanoparticles) and lipid o/w emulsions regarding the chemical composition and the preparation method, there are basic differences in the physicochemical behaviour of these systems. Phospholipid stabilized tripalmitate suspensions with a composition similar to commercial lipid emulsions for parenteral nutrition tend to form semi-solid ointment-like gels. Gel formation can be attributed to the recrystallization of melt-homogenized tripalmitate. As observed by transmission electron microscopy, recrystallization is associated with an increase in specific interfacial area due to the formation of anisometrical, platelet-like colloidal crystals with structured surfaces. Due to the limited mobility of phospholipid molecules in excess which form predominantly vesicles in the aqueous phase these emulsifiers are not able to immediately cover the newly created interfaces during platelet formation in an efficient way. Phospholipid molecules seem to be preferably associated with specific crystal interfaces during recrystallization causing variations in polarity and atomic/molecular order of different nanocrystal faces. Crystal interfaces with low concentrations of adsorbed emulsifier molecules represent preferred sites of particle aggregation over which gel formation can proceed. Gel formation can be prevented by the addition of co-emulsifying agents to the aqueous phase provided the concentration of co-surfactant is sufficiently high to constitute a reservoir of molecules immediately available for interfacial stabilization during recrystallization. Moreover, the co-emulsifier should preferably adsorb on crystal interfaces not or only incompletely covered by phospholipids.