Preparation of melatonin novel-mucoadhesive nanoemulsion used in the treatment of depression

In this current research work has a main aim to develop a novel Melatonin (MLT: BCS class II drug)-loaded nanoemulsion for the improvement in solubility. A developed novel-NE was to evaluate and compare the efficacy of Melatonin-loaded mucoadhesive nanoemulsion (CS-MLT-NE) with Melatonin-loaded nanoemulsion (MLT-NE) and MLT-solution (MLT-S) pharmacodynamically and also determine the quantity of MLT in the brain after the nasal administration. MLT-NE was prepared with the help of an advanced ultrasonication method after the screening of excipients and the development of pseudoternary phase diagram study. We got the optimized nanoformulation via three-factor four-level central-composite design (CCD). We optimized %oil, %S-mix, and sonication time (second) based on selected independent variables. Independent and dependent variables were selected and optimized on the basis constraints oil (2.0%), 10%S-mix, and 120 s sonication time. The dependent variables found the experimental their values 49.37 +/- 4.09 nm (Y-1: Globule size), 0.257 +/- 0.0004 (Y-2: PDI), - 16.20 +/- 1.10 mV (Y-3: Zeta Potential), and 98.03 +/- 0.59% (Y-4: %Transmittance), respectively. The shape of optimized-MLT-NE was found spherical with the pH, viscosity, and drug content (7.40 +/- 0.08, 37.86 +/- 7.01 cp, and 98.27 +/- 0.17%), respectively. Zeta-Potential of CS-MLT-NE was altered from -ve to +ve after the addition of CS followed small increment of globule-size. CS-MLT-NE showed the great mucoadhesive nature as compared to MLT-NE, and MLT-S with a retention time of 0.641 min and m/z of 233.20/174.20 for MLT. A linear range was established from 0.50 to 1500.0 ng mL(-1) with %accuracy (92.41-98.61%) and inter- and intraday %precision (2.49-4.93%). C-max was enhanced (AUC)(0-24) which was greatly significant (p < 0.001) in the rat's brain when it compared with i.n. and intravenous-treated group. Moreover, FST (forced swimming, climbing, and immobility) and locomotor activity test of CS-MLT-NE (i.n.) showed highly improved behavioral analysis as compared to the MLT-NE and MLT-S after 24.0 h of study. CS-MLT-NE showed highly significant role (p < 0.001) for the improvement in brain bioavailability and treatment of depression. [GRAPHICS] .

Automated summary

The study aims to develop a novel Melatonin-loaded nanoemulsion for improved solubility, and evaluate its efficacy and brain bioavailability in comparison to other forms of Melatonin. The optimized nanoformulation showed significant improvement in the treatment of depression, indicating the potential of this nanoemulsion.