title: How relevant are assembled equilibrium samples in understanding structure formation during lipid digestion?
abstract: Lipid-based formulations are gaining interest for use as drug delivery systems for poorly water-soluble drug compounds. During digestion, the lipolysis products self-assemble with endogenous surfactants in the gastrointestinal tract to form colloidal structures, enabling enhanced drug solubilisation. Although earlier studies in the literature focus on assembled equilibrium systems, little is known about structure formation under dynamic lipolysis conditions. The purpose of this study was to investigate the likely colloidal structure formation in the small intestine after the ingestion of lipids, under equilibrium and dynamic conditions. The structural aspects were studied using small angle X-ray scattering and dynamic light scattering, and were found to depend on lipid composition, lipid chain length, prandial state and emulsification. Incorporation of phospholipids and lipolysis products into bile salt micelles resulted in swelling of the structure. At insufficient bile salt concentrations, a co-existing lamellar phase was observed, due to a reduction in the solubilisation capacity for lipolysis products. Emulsification accelerated the rate of lipolysis and structure formation.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Phan
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Salentinig
authors.affiliation: SAXS/WAXS Beamline, Australian Synchrotron, 800 Blackburn Road, Clayton, VIC 3168, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hawley
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: ben.boyd@monash.edu.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism; D003102:Colloids; D004063:Digestion / Q000502:physiology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000378:metabolism; D005766:Gastrointestinal Contents / Q000737:chemistry; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism*; D008027:Light; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D008066:Lipolysis / Q000502:physiology*; D008954:Models, Biological; D050178:Monoglycerides / Q000737:chemistry / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D053838:Scattering, Small Angle; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D001647:Bile Acids and Salts; D003102:Colloids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D050178:Monoglycerides; D004364:Pharmaceutical Preparations; D010743:Phospholipids
keywords: High performance liquid chromatography; In vitro lipolysis; Lipid digestion; Lipid-based drug delivery; Small angle X-ray scattering