Walaa A El-Dakroury, 1 Yousra A Nomier, 2 Abdelrahman R Said, 1 Magaji Garba Taura, 3 Ahmed Soliman Doghish, 4, 5 Asem Shalaby, 6 Omnia M Sarhan1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt; 2Pharmacology and Clinical Pharmacy Department, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman; 3Department of Anatomy, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia; 4Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, 11651, Egypt; 5Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo, Badr City, Cairo, 11829, Egypt; 6Pathology Department, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, OmanCorrespondence: Walaa A El-Dakroury, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt, Email walaa. ahmed2@buc. edu. eg; wdakroury@yahoo. com Yousra A Nomier, Pharmacology and Clinical Pharmacy Department, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman, Email y. nomeir@squ. edu. omIntroduction: Chitosan-pimelate (CS-Pim) mucoadhesive buccal films were developed to improve the therapeutic efficacy of duloxetine (DLX) using sage oil-based lipid carriers (DLX-SLCs). This buccal nanoplatform addresses DLXâs limited oral bioavailability and extensive first-pass metabolism by providing a non-invasive route with enhanced mucosal permeability and sustained release. Methods: DLX-SLCs were optimized and characterized for particle size, zeta potential, and entrapment efficiency. The carriers incorporated into CS-Pim buccal films, which were evaluated for physicochemical properties, morphology, hydrophilicity, and mucoadhesive strength. In vivo antidepressant efficacy was assessed in a lipopolysaccharide (LPS) -induced rat depression model using behavioral tests, biochemical markers, and histopathological analysis. Results: Optimized DLX-SLCs yielded an average size of 130. 9± 2. 4 nm, zeta potential of â 28. 4 ± 2. 3 mV, and entrapment efficiency of 79. 9 ± 3. 8%. The selected film exhibited desirable physicochemical attributes, including uniform thickness, pH (7. 08 ± 0. 03), drug content (99. 1 ± 0. 4%), tensile strength (10. 07 ± 0. 34 N/cm2), elongation at break (109. 9 ± 7. 3%), swelling index (124%), mucoadhesive strength (48. 9 ± 2. 38 g), and smooth surface via SEM. FTIR and DSC confirmed successful polymer modification, drug encapsulation, and amorphous dispersion of DLX within the matrix. Contact angle analysis confirmed improved hydrophilicity. DLX-SLCs buccal films exhibited superior curative efficacy compared to pure-DLX and the marketed-DLX in lipopolysaccharide (LPS) -induced rat depression model. Behavioral assessments demonstrated a 60% reduction in immobility time, an increase in open-arm entries, and sucrose preference by a 3. 29-fold and 2-fold, respectively, compared to the LPS group. Biochemical analyses revealed reduced TNF-α, IL-1β, and cortisol levels by 67. 6%, 64. 4%, and 53%, respectively. Alongside increased serotonin and GABA levels by 1. 64-fold and 3. 5-fold, respectively. Histopathological findings confirmed significant neuroprotective effects. Conclusion: DLX-SLCs incorporated into CS-Pim buccal films provide enhanced antidepressant efficacy and neuroprotective benefits, representing a bioadhesive and patient-compliant alternative to conventional DLX formulations for depression treatment. Keywords: antidepressant, buccal, chitosan, duloxetine, mucoadhesion, pimelic acid
El‐Dakroury et al. (Thu,) studied this question.