Solid Lipid Nanoparticles Incorporating Melatonin as New Model for Sustained Oral and Transdermal Delivery Systems

Abstract

Introduction: 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 × hour vs. 85148.4 ± 50642.6 pg/ml × 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.

Solid lipid nanoparticles for thermoresponsive targeting: evidence from spectrophotometry, electrochemical, and cytotoxicity studies

“…1,8 On the other hand, solid lipid nanoparticles (SLNs) have been reported to show long circulation life (24 hours) and passively target cancers by enhanced permeability and retention (EPR) effect. 9,10 In addition to this, SLN composition and their methods of preparation are considered safe as compared to other novel DDS such as liposomes. 11 Previously, SLNs have been used in combination with hydrogels to achieve thermoresponsive drug delivery.…”

Recent Advances in Lipid Nanoparticle Formulations with Solid Matrix for Oral Drug Delivery

“…Pharmacokinetics of melatonin after oral and transdermal administration of melatonin-loaded SLNs in human were performed (102). The aim of this study was to make SLN as a drug reservoir, permitting a constant and prolonged release of the incorporated drug.…”

Encapsulation of Polyunsaturated Fatty Acid Esters with Solid Lipid Particles

“…Pharmaceutical applications for solid lipid particles include oral, parenteral, and topical drug delivery. 7,[10][11][12][13][14][15][16][17][18] Advantages include improved bioavailability, controlled release, and stabilization. Limitations include drug loading capacity and reports of drug expulsion during storage.…”