ArticleIranian journal of basic medical sciences2026
Enhancing clomipramine antidepressive effect using nanocomplexes via different routes of administration: A comparative study.
Article in Iranian journal of basic medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: Enhancing clomipramine anti-depressive effect using a nanoformulation and investigating its effect via different routes of administration (oral and intranasal) in a depression rat model. Polyelectrolytes nanocomplexes (NC) were prepared by an all-aqueous technique and were composed of different ratios of chitosan (CS) and gum arabic (GA). Materials and Methods: Ciprofloxacin (CPX) was administered orally to adult male Wistar albino rats at a dose of 50 mg/kg for 14 days to induce depression. Clomipramine HCl solution and the drug-loaded nano complexes (NC) were administrated for 14 days via the oral route (50 mg/kg) and intranasal route (500 µg/kg). Results: All the prepared drug-loaded nano-complexes (NC) were uniformly distributed (PDI ˂0.2), NC1 (composed of CS:GA 1:1) attained the smallest particle size (200.30 ± 26.07nm) and the most sustained release profile (Mean Release Time= 96.02± 8.36 min.) and has a spherical outline as detected by transmission electron microscope. Treatment with clomipramine-loaded NC via oral and intranasal routes elevated swimming time, serotonin (5-HT), excitatory amino acid transporter 2 (EAAT2) and Gamma-aminobutyric acid (GABA) brain contents, decreased brain content of malondialdehyde (MDA) and nitric oxide (NO), and ameliorated nuclear pyknosis and degeneration of neurons compared to CPX and clomipramine solution. Clomipramine-loaded NC via intranasal routes returned the brain content of 5-HT and EAAT 2 to its normal level and has effect superior than oral route. Conclusion: Clomipramine-loaded NC administered via intranasal route showed an enhanced effect and a higher antidepressant activity than the traditional oral route through alleviating CPX neurological toxicity.
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