title: Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems.
abstract: melatonin (MT) is a hormone produced by the pineal gland at night, involved in the regulation of circadian rhythms. For clinical purposes, exogenous MT administration should mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favourable due to short half-life of elimination. Aim of this study is to examine pharmacokinetics of MT incorporated in solid lipid nanoparticles (SLN), administered by oral and transdermal route. SLN peculiarity consists in the possibility of acting as a reservoir, permitting a constant and prolonged release of the drugs included. In 7 healthy subjects SLN incorporating MT 3 mg (MT-SLN-O) were orally administered at 8.30 a.m. MT 3 mg in standard formulation (MT-S) was then administered to the same subjects after one week at 8.30 a.m. as controls. In 10 healthy subjects SLN incorporating MT were administered transdermally (MT-SLN-TD) by the application of a patch at 8.30 a.m. for 24 hours. Compared to MT-S, Tmax after MT-SLN-O administration resulted delayed of about 20 minutes, while mean AUC and mean half life of elimination was significantly higher (respectively 169944.7 +/- 64954.4 pg/ml x hour vs. 85148.4 +/- 50642.6 pg/ml x hour, p = 0.018 and 93.1 +/- 37.1 min vs. 48.2 +/- 8.9 min, p = 0.009). MT absorption and elimination after MT-SLN-TD demonstrated to be slow (mean half life of absorption: 5.3 +/- 1.3 hours; mean half life of elimination: 24.6 +/- 12.0 hours), so MT plasma levels above 50 pg/ml were maintained for at least 24 hours. This study demonstrates a significant absorption of MT incorporated in SLN, with detectable plasma level achieved for several hours in particular after transdermal administration. As dosages and concentrations of drugs included in SLN can be varied, different plasma level profile could be obtained, so disclosing new possibilities for sustained delivery systems.
authors.affiliation: Divisione di Neurologia e Neuroriabilitazione, Osp. S. Giuseppe, IRCCS Istituto Auxologico Italiano, Piancavallo (VB), Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Priano
authors.forename: Daniele
authors.initials: D
authors.lastname: Esposti
authors.forename: Roberto
authors.initials: R
authors.lastname: Esposti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Castagna
authors.forename: Clotilde
authors.initials: C
authors.lastname: De Medici
authors.forename: Franco
authors.initials: F
authors.lastname: Fraschini
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Gasco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mauro
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008550:Melatonin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D008550:Melatonin