STRUCTURE AND FUNCTION OF GASTROINTESTINAL LIPASES

Fat digestion in the gastro-intestinal tract is likely to have a profo und 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 gast ro-intestinal tract. Topics discussed include emulsification in the st omach, structure and function of gastro-intestinal lipases and colipas e, phase behaviour and physicochemical properties of lipids and lipoly tic products, and the absorption of lipolytic products across the brus h border of the enterocyte. The physical chemistry of lipolysis has be en well documented and in recent years there have been significant adv ances in the understanding of lipolysis at the molecular level, with p ublication of crystal structures of the pancreatic lipase-colipase com plex, both in the presence and absence of lipids. The crystal structur es have explained the activation of lipases by triglyceride interfaces and the role of colipase in lipolysis. Tetraethylene glycol mono-octy l 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 activit y to play a role by inhibiting binding of lipase-colipase to emulsion droplets.