Modulating the Lipase-Mediated Bioactivity of Particle-Lipid Conjugates Through Changes in Nanostructure and Surface Chemistry

Journal article, 2017

The lipase-mediated hydrolysis of triglycerides can be controlled by confining lipid droplets within highly porous nanostructured particle matrices. Novel hybrid materials with varying bioactivities toward lipase have been developed by spray drying particle-stabilized emulsions to form highly organized three-dimensional architectures. In this study, the particle size, nanostructure, and surface chemistry of hybrid particles are tailored to systematically investigate the influence of material characteristics on lipase activity. This is achieved by varying (i) the spray drying process and (ii) the structure and composition of particulate colloids employed to stabilize the precursor emulsions. In all cases, the colloidal self-assembly of particles and droplets into nanostructured conjugates during the water removal process facilitated enhanced lipase activity compared to submicron triglyceride emulsions, with lipolysis kinetics increasing in the following order: polymer-lipid hybrid (PLH) < silica-lipid hybrid (SLH) ? clay-lipid hybrid (CLH). Lipase activity increased as a function of increasing interfacial surface area of the lipid substrate and increasing hydrophilicity of the solid matrix support. The novel insights into the role of hybrid particle nanostructure and surface chemistry on the mechanism of lipase action can be harnessed for the intelligent design of new and improved lipid-based drug delivery vehicles and functional foods. Practical Applications: Understanding and controlling the interaction between triglyceride molecules and pancreatic lipase is of fundamental importance for the rational design of new functional foods and drug formulations. Lipid digestion in the body facilitates the delivery of fat and encapsulated bioactive compounds from the gastrointestinal tract (GIT) to the blood and surrounding tissues. Hence, the bioavailability of poorly soluble compounds can be controlled by engineering lipid-based systems that regulate lipase activity. In this study, three novel solid-state systems have been designed that finely control the catalytic activity of lipase, and therefore, demonstrate high commercial potential within the pharmaceutical and biotechnology industries. The lipase-mediated hydrolysis of triglycerides is controlled by designing novel solid-state particle-lipid conjugates with unique nanostructures and surface chemistries. The hybrid materials are prepared by spray-drying particle-stabilized lipid droplets, which induced the forced agglomeration of particles and droplets into micron-sized particles with distinctive three-dimensional architectures. The ability to modulate lipase activity through material design presented novel insights into the mechanism of digestive enzyme action, which is of fundamental importance for the rational design of new functional foods and drug formulations.