Formation of highly structured cubic micellar lipid nanoparticles of soy phosphatidylcholine and glycerol dioleate and their degradation by triacylglycerol lipase

Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I2) structure show good drug loading ability of peptides and proteins as well as some small molecules. Due to their controllable small size and inner morphology, such nanoparticles are suitable for drug delivery using several different administration routes, including intravenous, intramuscular and subcutaneous injection. A very interesting system in this regard, is the two component soy phosphatidylcholine (SPC)/glycerol dioleate (GDO) system, which depending on the ratio of the lipid components form a range of reversed liquid crystalline phases. For a 50/50 (wt/wt) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I2) phase of the Fd3m structure. Here we demonstrate that this SPC/GDO phase, in the presence of small quantities (5-10 wt%) of Polysorbate 80 (P80), can be dispersed into nanoparticles, still with well-defined Fd3m structure. The resulting nanoparticle dispersion has a narrow size distribution and exhibit good long-term stability. In pharmaceutical applications, biodegradation pathways of the drug delivery vehicles and their components are important considerations. In the second part of the study we show how the structure of the particles evolves during exposure to a triacylglycerol lipase (TGL) under physiological-like temperature and pH. TGL catalyses the lipolytic degradation of acylglycerides, such as GDO, to monoglycerides, glycerol and free fatty acids. During the degradation, the interior phase of the particles is shown to undergo continuous phase transitions from the reversed I2 structure to structures of less negative curvature (2D hexagonal, bicontinuous cubic and sponge), ultimately resulting in the formation of multi-lamellar vesicles

Protein/Emulsifier Interactions

An important consequence of protein-lipid interaction is the effect on stability of the protein in solution as well as on its behavior at interfaces. Here we will discuss key aspects of protein aggregation and unfolding as well as the effects of protein structure (random coil proteins versus globular) that are relevant for our understanding protein-lipid interaction. The main types of emulsifiers are the (1) aqueous soluble, surfactant type and (2) lipids with low aqueous solubility. The monomer concentration as defined by cmc is an important parameter for the soluble lipids. For emulsifiers with low aqueous solubility the emulsifier self-assembly structure and its properties control the interaction with proteins. We will therefore summarize the main features of lipid self-assembly. It also allows us to define different plausible scenarios and principles and models for factors that control the interactions in real food (and Pharmaceutical) systems. For the food applications the fate of the lipid during digestion is important and therefore we will discuss some aspects of enzyme-catalyzed lipolysis in terms of the structural evolution. New products and concepts of using protein/emulsifier interactions will be exemplified by illustrating how food nanotechnology possibly can be used for the delivery of functionality