title: Impact of Lipid-Based Drug Delivery Systems on the Transport and Uptake of Insulin Across Caco-2 Cell Monolayers.
abstract: Self-(nano)-emulsifying drug delivery systems (SNEDDSs) used to deliver peptides and proteins across biological barriers, such as the small intestinal membrane, represents an increasingly interesting field in nanomedicine. Hence, the present study was designed to evaluate the impact of SNEDDS on the transport and uptake mechanisms of insulin across the intestinal membrane. For this purpose, 3 SNEDDS were prepared, and Caco-2 cell monolayers were used to study transport and uptake. The prepared SNEDDSs were all in the range of 35-50 nm and had a negative zeta potential (between -8 and -25 mV). The entrapment of insulin on dispersion in the experimental media ranged from 40% to 78% for all SNEDDSs. Fluorescent microscopy studies indicated that fluorescein isothiocyanate-labeled insulin when administered in solution, as well as when loaded into MCT1 or MCT2 SNEDDS, localized within the intercellular space of the Caco-2 cell monolayer, indicating transport by paracellular diffusion. In contrast, the fluorescein isothiocyanate-labeled insulin in LCT SNEDDS was taken up by the cells. In conclusion, the present study demonstrated that MCT1 and MCT2 SNEDDS, but not LCT SNEDDS increased the transepithelial permeability of insulin, via the paracellular route.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Hanne Mørck
authors.initials: HM
authors.lastname: Nielsen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark; Bioneer: FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address: Anette.Mullertz@sund.ku.dk.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005227:Fatty Acids / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D014280:Triglycerides / Q000737:chemistry
chemical_list: D004655:Emulsions; D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; C031573:insulin, fluorescein-isothiocyanated-; D016650:Fluorescein-5-isothiocyanate
keywords: Caco-2 cells; emulsion; lipids; oral drug delivery; paracellular transport; permeation enhancers; proteins; self-emulsifying; transcellular transport