Labrasol® is an efficacious intestinal permeation enhancer across rat intestine: Ex vivo and in vivo rat studies
| Autor: | Vincent Jannin, Fiona McCartney, Cédric Miolane, Nicolas Ritter, Frédéric Demarne, Delyan R. Hristov, Hakime Boulghobra, David J. Brayden, Yann Chavant, Stéphanie Chevrier |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Colon Pharmaceutical Science 02 engineering and technology Polyethylene glycol In Vitro Techniques Glycerides Tight Junctions Excipients 03 medical and health sciences chemistry.chemical_compound In vivo PEG ratio medicine Animals Intestinal Mucosa Rats Wistar 030304 developmental biology Labrasol® ALF chemistry.chemical_classification 0303 health sciences Chromatography Ussing chamber Fatty acid 021001 nanoscience & nanotechnology Rats Bioavailability Jejunum Intestinal Absorption chemistry Oral peptide delivery Paracellular transport Intestinal permeation enhancers Mannitol Epithelial tight junctions 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Controlled Release. 310:115-126 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2019.08.008 |
| Popis: | Labrasol® ALF (Labrasol®), is a non-ionic surfactant excipient primarily used as a solubilising agent. It was investigated here as an intestinal permeation enhancer in isolated rat colonic mucosae in Ussing chamber and in rat in situ intestinal instillations. Labrasol® comprises mono-, di- and triglycerides and mono- and di- fatty acid esters of polyethylene glycol (PEG)-8 and free PEG-8, with caprylic (C8)- and capric acid (C10) as the main fatty acids. Source components of Labrasol® as well as Labrasol® modified with either C8 or C10 as the sole fatty acid components were also tested to determine which element of Labrasol® was responsible for its permeability-enhancing properties. Labrasol® (4, 8 mg/ml) enhanced the transport of the paracellular markers, [14C] mannitol, FITC-dextran 4000, and FITC-insulin across colonic mucosae. The enhancement was non-damaging, transient, and molecular weight-dependent. The PEG ester fraction of Labrasol® also had enhancing properties. When insulin was administered with Labrasol® in instillations, it had a relative bioavailability of 7% in jejunum and 12% in colon. C8- and C10 versions of Labrasol® and the PEG ester fraction also induced similar bioavailability values in jejunal instillations: 6, 5 and 7% respectively. Inhibition of lipases in instillations did not reduce the efficacy of Labrasol®, suggesting that its mechanism as a PE is not simply due to liberated medium chain fatty acids. Labrasol® acts as an efficacious intestinal permeation enhancer and has potential for use in oral formulations of macromolecules and BCS Class III molecules. Gattefosse SAS |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect