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

• প্রধান লেখক: Irene Moroni (Author), Alfonso E. Garcia-Bennett (Author)
• বিন্যাস: গ্রন্থ
• প্রকাশিত: MDPI AG, 2021-09-01T00:00:00Z.
• বিষয়গুলি: article
• অনলাইন ব্যবহার করুন: Connect to this object online.
• Notes: 10.3390/pharmaceutics13091436; 1999-4923
• Keywords: melatonin; drug delivery; mesoporous silica; catabolism; bioavailability; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 9, p 1436 (2021)

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.