Structure and function of gastro-intestinal lipases

Fat digestion in the gastro-intestinal tract is likely to have a profound influence on the bioavailability of drugs from oily drug delivery systems. Many of the excipients used in such formulations are natural triglycerides or semi-synthetic digestible esters of fatty acids. This article summarises the current knowledge of fat digestion in the gastro-intestinal tract. Topics discussed include emulsification in the stomach, structure and function of gastro-intestinal lipases and colipase, phase behaviour and physicochemical properties of lipids and lipolytic products, and the absorption of lipolytic products across the brush border of the enterocyte. The physical chemistry of lipolysis has been well documented and in recent years there have been significant advances in the understanding of lipolysis at the molecular level, with publication of crystal structures of the pancreatic lipase-colipase complex, both in the presence and absence of lipids. The crystal structures have explained the activation of lipases by triglyceride interfaces and the role of colipase in lipolysis. Tetraethylene glycol mono-octyl ether is able to interact with lipase in an analogous manner to the substrate, which may explain the inhibitory effects of surfactants on lipolysis, although one would also expect non-specific surface activity to play a role by inhibiting binding of lipase-colipase to emulsion droplets.