TY - JOUR
T1 - Preparation of melatonin novel-mucoadhesive nanoemulsion used in the treatment of depression
AU - Ahmad, Niyaz
AU - Khalid, Mohammed Saifuddin
AU - Al Ramadhan, Ayman Makki
AU - Alaradi, Mohammed Zaki
AU - Al Hammad, Mohammed Riyad
AU - Ansari, Khalid
AU - Alqurashi, Yousef D.
AU - Khan, Mohd Faiyaz
AU - Albassam, Ahmed A.
AU - Ansari, Mohammad Javed
AU - Akhtar, Sultan
AU - Dilshad, Mubah
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/7
Y1 - 2023/7
N2 - Abstract: 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, %Smix, 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%Smix, 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%). Cmax 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. Graphical abstract: [Figure not available: see fulltext.].
AB - Abstract: 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, %Smix, 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%Smix, 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%). Cmax 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. Graphical abstract: [Figure not available: see fulltext.].
KW - Brain bioavailability
KW - Depression study
KW - Melatonin
KW - Mucoadhesive nanoemulsion
KW - Three-factor four-level central-composite design (CCD)
KW - UHPLC-MS/MS-based bioanalytical method
KW - Ultrasonication technique
UR - http://www.scopus.com/inward/record.url?scp=85137215021&partnerID=8YFLogxK
U2 - 10.1007/s00289-022-04436-3
DO - 10.1007/s00289-022-04436-3
M3 - Article
AN - SCOPUS:85137215021
SN - 0170-0839
VL - 80
SP - 8093
EP - 8132
JO - Polymer Bulletin
JF - Polymer Bulletin
IS - 7
ER -