TY - JOUR
T1 - A Dual Nanoapproach for the Treatment of Depression and Sleep Via a Novel Optimized Eugenol-Mucoadhesive Nanoemulsion
AU - Khan, Mohd Faiyaz
AU - Ahmad, Niyaz
AU - Ansari, Khalid
AU - Ullah, Zabih
AU - Ibrahim, Hisham Osman
AU - Alyami, Hanan Mesfer
AU - Alqahtani, Ali Jaber
AU - Ahmad, Sarfaraz
N1 - Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society.
PY - 2025/4/29
Y1 - 2025/4/29
N2 - This study aimed to develop a chitosan (CHS)-coated eugenol (EUGE)-loaded nanoemulsion (CHS-EUGE-NE) to enhance brain bioavailability. A novel GC-MS/MS method was developed and validated for EUGE quantification in brain tissue and plasma alongside pharmacokinetic analysis. The nanoemulsion was optimized using a Box-Behnken design (BBD), with the final formulation containing 6.0% oil, 10% surfactant mix, and undergoing 6.5 min of ultrasonication at 30% intensity and 40 °C. The optimized CHS-EUGE-NE exhibited a globule size of 142.4 ± 11.31 nm, a polydispersity index of 0.1660 ± 0.0009, and a zeta potential of −16.20 ± 1.10 mV, which shifted to positive upon CHS coating, enhancing mucoadhesion. A linear range from 1.00 to 3000 ng/mL was established, with accuracy between 90.91% and 99.83%. Pharmacokinetic analysis demonstrated significantly increased Cmax and AUC in the rat brain, correlated with behavioral improvements in the forced swimming test. No signs of toxicity were observed. These findings suggest that CHS-EUGE-NE is a promising nanoformulation for enhancing the brain-targeted delivery of eugenol for the treatment of depression and sleep disorders.
AB - This study aimed to develop a chitosan (CHS)-coated eugenol (EUGE)-loaded nanoemulsion (CHS-EUGE-NE) to enhance brain bioavailability. A novel GC-MS/MS method was developed and validated for EUGE quantification in brain tissue and plasma alongside pharmacokinetic analysis. The nanoemulsion was optimized using a Box-Behnken design (BBD), with the final formulation containing 6.0% oil, 10% surfactant mix, and undergoing 6.5 min of ultrasonication at 30% intensity and 40 °C. The optimized CHS-EUGE-NE exhibited a globule size of 142.4 ± 11.31 nm, a polydispersity index of 0.1660 ± 0.0009, and a zeta potential of −16.20 ± 1.10 mV, which shifted to positive upon CHS coating, enhancing mucoadhesion. A linear range from 1.00 to 3000 ng/mL was established, with accuracy between 90.91% and 99.83%. Pharmacokinetic analysis demonstrated significantly increased Cmax and AUC in the rat brain, correlated with behavioral improvements in the forced swimming test. No signs of toxicity were observed. These findings suggest that CHS-EUGE-NE is a promising nanoformulation for enhancing the brain-targeted delivery of eugenol for the treatment of depression and sleep disorders.
UR - http://www.scopus.com/inward/record.url?scp=105003810866&partnerID=8YFLogxK
U2 - 10.1021/acsomega.5c00783
DO - 10.1021/acsomega.5c00783
M3 - Article
AN - SCOPUS:105003810866
SN - 2470-1343
VL - 10
SP - 16815
EP - 16840
JO - ACS Omega
JF - ACS Omega
IS - 16
ER -