title: Evaluation of cationic nanosystems with melatonin using an eye-related bioavailability prediction model.
abstract: In this study, two types of nanosystems, namely lecithin/chitosan nanoparticles and Pluronic® F127/chitosan micelles, have been prepared and evaluated for their potential for the ocular delivery of melatonin, which is known to exert an ocular hypotensive effect. The melatonin content, particle size, zeta potential and in vitro drug release properties were studied as a function of the presence of chitosan in the nanosystem. Lecithin/chitosan nanoparticles were evaluated in terms of the mucoadhesive properties by a newly established method based on HCE-T cells, also used in in vitro biocompatibility and permeability studies. Lecithin/chitosan nanoparticles were significantly larger than the corresponding F127/chitosan micelles (mean diameter of 241.8 vs. 20.7nm, respectively) and characterised by a higher surface charge (22.7 vs. 4.3mV, respectively). The HCE-T cell viability assay did not show significant toxic effects of nanosystems investigated at the (relevant) chitosan concentration tested. The permeability study results confirmed the permeation enhancing effect of F127, which was hindered in the presence of chitosan. Lecithin/chitosan nanoparticles were characterised by prominent mucoadhesive properties and prolonged melatonin release, which was shown to control melatonin permeation across an in vitro corneal epithelial model. Such properties demonstrate the potential for nanoparticles to provide an extended pre-corneal residence time of melatonin, ensuring higher eye-related bioavailability and extended intraocular pressure reduction compared to melatonin in both aqueous and micelle solutions.
authors: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia. Electronic address: ahafner@pharma.hr.
authors: Anita
authors: A
authors: Hafner
authors: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.
authors: Jasmina
authors: J
authors: Lovrić
authors: R&D, PLIVA Croatia Ltd, TEVA Group Member, Zagreb, Croatia.
authors: Marieta Duvnjak
authors: MD
authors: Romić
authors: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.
authors: Marina
authors: M
authors: Juretić
authors: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.
authors: Ivan
authors: I
authors: Pepić
authors: R&D, PLIVA Croatia Ltd, TEVA Group Member, Zagreb, Croatia.
authors: Biserka
authors: B
authors: Cetina-Čižmek
authors: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.
authors: Jelena
authors: J
authors: Filipović-Grčić
mesh_terms: D000268:Adhesiveness; D060433:Administration, Ophthalmic; D001682:Biological Availability; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D006801:Humans; D054709:Lecithins / Q000737:chemistry; D008550:Melatonin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008823:Micelles; D008954:Models, Biological; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010539:Permeability; D020442:Poloxamer / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D054709:Lecithins; D008823:Micelles; D020442:Poloxamer; D048271:Chitosan; D008550:Melatonin
keywords: Cationic nanosystems; Chitosan; Lecithin; Melatonin; Ocular drug delivery; Pluronic® F127