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

Abstract

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.

Microporosity, Pore Size, and Diffusional Path Length Modulate Lipolysis Kinetics of Triglycerides Adsorbed onto SBA-15 Mesoporous Silica Particles

“…Previous studies have been dedicated to elucidating the impact of the silica surface area and surface chemistry on lipase-mediated digestion of the lipid confined within commercially available silica particles, comprised of poorly defined porous networks. 29,30 It was established that lipolysis kinetics are enhanced within hydrophilic porous silica particles because of the (i) increased surface area of the lipidin-water interface, (ii) adsorption of both lipid and lipase molecules in a favorable orientation for maximum catalytic activity, and (iii) effective removal of fatty acids (FAs) from the lipid-in-water interface, preventing competitive inhibition with the lipase molecules. 29,31 Despite the emergence of silica-lipid hybrid particles as carriers for controlling lipase-mediated digestion, the impact of fundamental and more specific silica structural properties on lipolysis kinetics is not yet clear.…”

“…A commonly used approach to control lipase-provoked digestion is to engineer solid-state carriers that encapsulate lipids within a particle matrix, thus altering the microstructure and bio-accessibility of the lipid-in-water interface. , Porous silica particles are one such particle carrier which have been extensively explored for their ability to host TGs in an environment that promotes changes to lipase activity. , Because of their readily tunable properties, such as porosity, particle size, and surface chemistry, it is possible to finely tune the interfacial activation mechanism of lipase to optimize lipolysis kinetics. Previous studies have been dedicated to elucidating the impact of the silica surface area and surface chemistry on lipase-mediated digestion of the lipid confined within commercially available silica particles, comprised of poorly defined porous networks. , It was established that lipolysis kinetics are enhanced within hydrophilic porous silica particles because of the (i) increased surface area of the lipid-in-water interface, (ii) adsorption of both lipid and lipase molecules in a favorable orientation for maximum catalytic activity, and (iii) effective removal of fatty acids (FAs) from the lipid-in-water interface, preventing competitive inhibition with the lipase molecules. , …”

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

“…It can be supposed that the lipase activity can be altered by formulation of lipids using PIs with varying physicochemical properties because PIs can influence on the lipid-water interface, hence, affecting interfacial activation mechanism of lipase [132][133][134]. For this reason, PIs can manipulate GI lipolysis via interactions between PIs and lipids, lipases, and lipid digested products.…”

Solidification to improve the biopharmaceutical performance of SEDDS: Opportunities and challenges

“…This occurs due to the presence a polypeptide loop that protects the mostly hydrophobic active site from the aqueous environment, until weak adsorption onto a liquid-in-liquid or solid-in-liquid interface triggers this lid domain to open, exposing the catalytic domains [143]. The interfacial activation mechanism establishes the potential to modulate lipase activity through colloidal and interfacial engineering of the lipid-in-water interface [144,145]. A proven approach to alter the bioaccessibility of lipid to digestive enzymes, is to formulate lipids with solid carriers with varying surface chemistry and nanostructure [146,147].…”

“…Adsorption of liquid-SEDDS excipients onto porous solid carriers can significantly manipulate the interfacial surface area of lipid, compared to conventional emulsion droplets. This has been shown extensively by confining digestible triglycerides within mesoporous silica particles [145][146][147][148][149][150][151], whereby the lipid-in-water interfacial area is relative to the lipid loading and relative porosity of the particles. A 4.5-fold improvement in lipolysis kinetics was observed when medium chain triglycerides were encapsulated within hydrophilic porous silica particles compared to a submicron emulsion, due to a 5.1fold increase in interfacial surface area [146].…”