New in vitro models to evaluate intestinal absorption of nanomedicines

• Κύριος συγγραφέας: Kaeokhamloed, Norraseth
• Άλλοι συγγραφείς: Κλεπετσάνης, Παύλος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Intestinal absorption model; Lipid nanocapsules; Vascular endothelium cell line HMEC-1; Εντερικό πρότυπο απορρόφησης; Λιπιδικές νανοκάψουλες; Κυτταρική σειρά αγγειακού ενδοθηλίου HMEC-1

The complex properties of nanoparticles that differ from conventional molecular drug necessitate the need for better in vitro cell culture model to study their absorption behavior. Standard models like Caco-2 seems to be inadequate because it consists of only one intestinal epithelium monolayer, ignoring the presences of vascular endothelium which is the part of complex multilayered barrier system. [1,2] The aim of this project is to develop new in vitro intestinal absorption model for nanomedicines which includes the vascular endothelium to better mimic actual structure of intestinal barriers, and then investigating the absorption of lipid nanocapsule (LNCs) which has the unique ability to absorb through the intestinal epithelial membrane.[3] Caco-2 cell lines were cultured on a collagen coated Transwell® insert (12 mm, polycarbonate, 0.4 μm pore size). After 18 days, vascular endothelium cell line HMEC-1 was cocultured for another 4 days on the lower side of the membrane filter to make a contact coculture system. The morphology was characterized by Transmission electron microscopy (TEM). Formation of cell junctions were monitored by transepithelial/endothelial resistance (TEER) and immunoassay of ZO-1 and β-catenin (cell junction proteins). The apparent permeability (Papp) of 6 drugs (metoprolol, propranolol, chlorpromazine, naproxen, atenolol and furosemide) according to the biopharmaceutics classification system (BCS) were investigated. Tricaprylin-based lipid nanocapsules (LNCs) were developed with different sizes (60 nm and 90 nm) and their Papp were also examined using Föster resonance energy transfer (FRET) technology.