Understanding the lipid-digestion Processes in the GI Tract Before Designing lipid-based drug-delivery Systems

Abstract

Many of the compounds present in lipid-based drug-delivery systems are esters, such as acylglycerols, phospholipids, polyethyleneglycol mono- and di-esters and polysorbate, which can be hydrolyzed by the various lipolytic enzymes present in the GI tract. Lipolysis of these compounds, along with dietary fats, affects the solubility, dispersion and bioavailibity of poorly water-soluble drugs. Pharmaceutical scientists have been taking a new interest in fat digestion in this context, and several studies presenting in vitro gastrointestinal lipolysis models have been published. In most models, it is generally assumed that pancreatic lipase is the main enzyme involved in the gastrointestinal lipolysis of lipid formulations. It was established, however, that gastric lipase, pancreatic carboxyl ester hydrolaze and pancreatic lipase-related protein 2 are the major players involved in the lipolysis of lipid excipients containing acylglycerols and polyethyleneglycol esters. These findings have shown that the lipolysis of lipid excipients may actually start in the stomach and involve several lipolytic enzymes. These findings should therefore be taken into account when testing in vitro the dispersion and bioavailability of poorly water-soluble drugs formulated with lipids. In this review, we present the latest data available about the lipolytic enzymes involved in gastrointestinal lipolysis and suggest tracks for designing physiologically relevant in vitro digestion models.

Acknowledgements

The authors wish to thank J Blanc for revising and perfecting the English language in this manuscript.

Financial & competing interest disclosure

V Jannin is an employee of Gattefossé SAS (Saint-Priest, France). We are grateful to Gattefossé SAS for supporting our research in the framework of a joint research contract with CNRS. This work was performed with the financial support of the LISA Carnot Institute, Agence Nationale de la Recherche (ANR; Convention n° 07-CARN-009-01) and the LFCS consortium (Lipid Formulation Classification System; www.lfcsconsortium.org/). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.