Effects of Absorption Kinetics on the Catabolism of Melatonin Released from CAP-Coated Mesoporous Silica Drug Delivery Vehicles.

Melatonin (MLT) is a pineal hormone involved in the regulation of the sleep/wake cycle. The efficacy of exogenous MLT for the treatment of circadian and sleep disorders is variable due to a strong liver metabolism effect. In this work, MLT is encapsulated in mesoporous silica (AMS-6) with a loading capacity of 28.8 wt%, and the mesopores are blocked using a coating of cellulose acetate phthalate (CAP) at 1:1 and 1:2 AMS-6/MLT:CAP ratios. The release kinetics of MLT from the formulations is studied in simulated gastrointestinal fluids. The permeability of the MLT released from the formulations and its 6-hydroxylation are studied in an in vitro model of the intestinal tract (Caco-2 cells monolayer). The release of MLT from AMS-6/MLT:CAP 1:2 is significantly delayed in acidic environments up to 40 min, while remaining unaffected in neutral environments. The presence of CAP decreases the absorption of melatonin and increases its catabolism into 6-hydroxylation by the cytochrome P450 enzyme CYP1A2. The simple confinement of melatonin into AMS-6 pores slightly affects the permeability and significantly decreases melatonin 6-hydroxylation. Measurable amounts of silicon in the basolateral side of the Caco-2 cell monolayer might suggest the dissolution of AMS-6 during the experiment.

Pharmacokinetics of exogenous melatonin in relation to formulation, and effects on sleep: A systematic review.

There is conflicting evidence on the clinical efficacy of exogenous melatonin for the treatment of sleep disorders. This may be due to differences in the pharmacokinetic (PK) properties of melatonin formulations used in clinical trials. The aim of this systematic review was to understand the relationship between melatonin formulations and PK parameters and, where possible, the effects on sleep outcomes. To this purpose, we conducted a systematic review and nineteen papers were included. The studies included three melatonin transdermal formulation, thirteen oral formulations, one topical, two buccal, two intravenous and two nasogastric formulations. Seven studies investigated the effect of the melatonin formulation on sleep and six of them found a significant improvement in one or more sleep parameters. The potential for an improved controlled release formulation that delays maximum concentration (Cmax) was identified. The different formulations and doses affect melatonin PK, suggesting that treatment efficacy maybe affected. Based on the current evidence, we are unable to provide recommendations of specific melatonin formulations and PK parameters for specific sleep disorders. Future studies should systematically investigate how different PK parameters of melatonin formulations affect efficacy treatment of sleep as well as circadian disorders.

A lysozyme corona complex for the controlled pharmacokinetic release of probucol from mesoporous silica particles.

Mesoporous silica particles (MSPs) enhance the release kinetics of poorly soluble compound probucol (PB) under the influence of a pore-blocking protein corona, prepared with lysozyme protein adsorption. In vivo oral administration experiments show a prolongation in the time to reach maximum systemic concentration and half-life of PB released from the lysozyme-MSP complex in comparison to the MSP alone. Specific hard protein corona complexes can act as functional diffusion barriers for the controlled release of drugs from MSP based formulations.