title: Melatonin-loaded lecithin/chitosan nanoparticles: physicochemical characterisation and permeability through Caco-2 cell monolayers.
abstract: In this study, the potential of lecithin/chitosan nanoparticles (NPs) as a mucoadhesive colloidal nanosystem for transmucosal delivery of melatonin was investigated. The size, zeta potential and melatonin loading of the lecithin/chitosan NPs were investigated as a function of lecithin type (Lipoid S45, S75 and S100) and chitosan content in the preparation. The NPs were characterised by mean diameter and zeta potential ranging between 121.6 and 347.5 nm, and 7.5 and 32.7 mV, respectively, and increasing with lecithin-negative charge and chitosan content in the preparation. Melatonin loadings were up to 7.1%. All NPs were characterised by prolonged release profiles with an initial burst (approximately 25%), followed by a slow release phase. Approximately 60-70% of melatonin was released in 4h. The permeability of melatonin was investigated using Caco-2 cells as an in vitro model of the epithelial barrier. Melatonin permeability from an NP suspension prepared with Lipoid S45 lecithin and a lecithin-to-chitosan weight ratio (L/C) of 20:1 (sample C2) was significantly improved compared to the permeability of melatonin from the solution (P<0.001) and from all other NPs investigated (P<0.05). The results obtained by the cell viability studies (MTT and LDH leakage assays) showed that C2 NP suspension did not induce plasma membrane damage or decrease cell viability and could be safely applied to Caco-2 cells in the concentration range tested (<400 microg/ml).
authors: Department of Pharmaceutics, Faculty of Pharmacy & Biochemistry, University of Zagreb, A. Kovacica 1, 10000 Zagreb, Croatia. ahafner@pharma.hr
authors: Anita
authors: A
authors: Hafner
authors: Jasmina
authors: J
authors: Lovrić
authors: Dario
authors: D
authors: Voinovich
authors: Jelena
authors: J
authors: Filipović-Grcić
mesh_terms: D000465:Algorithms; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D003102:Colloids / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D017097:Electric Impedance; D055664:Electrochemical Techniques; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D054709:Lecithins / Q000737:chemistry* / Q000378:metabolism; D008550:Melatonin / Q000737:chemistry* / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D012995:Solubility; D013535:Suspensions / Q000737:chemistry / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003102:Colloids; D004337:Drug Carriers; D054709:Lecithins; D009077:Mucins; D013535:Suspensions; D048271:Chitosan; D008550:Melatonin