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 (Y₁: Globule size), 0.257 ± 0.0004 (Y₂: PDI), − 16.20 ± 1.10 mV (Y₃: Zeta Potential), and 98.03 ± 0.59% (Y₄: %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.

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Ahmad, N., Khalid, M.S., Al Ramadhan, A.M. et al. Preparation of melatonin novel-mucoadhesive nanoemulsion used in the treatment of depression. Polym. Bull. (2022).
https://doi.org/10.1007/s00289-022-04436-3