1Research Scholar, Faculty of Pharmacy, Oriental University, Indore. Email: rajatrj776@gmail.com
2Associate Professor, Faculty of Pharmacy, Oriental University, Indore
3Professor & Principal, Faculty of Pharmacy, Oriental University, Indore
*Corresponding Author: Shikhar Rathore, Research Scholar, Faculty of Pharmacy, Oriental University, Indore. Email: rajatrj776@gmail.com
Background: Anxiety disorders are complex neuropsychiatric conditions associated with oxidative stress, neuroinflammation, neurotransmitter imbalance, and impaired neuroplasticity, and the therapeutic utility of clozapine is often limited by poor aqueous solubility and variable oral bioavailability. The present study evaluated the anxiolytic and neuroprotective potential of an optimized clozapine liqui-solid formulation in a caffeine-induced anxiety model in Wistar rats.
Methods: The study was conducted for 14 consecutive days using four groups: control, negative control treated with caffeine (30 mg/kg, i.p.), standard treated with diazepam, and a test group treated with clozapine liqui-solid formulation (10 mg/kg, p.o.). Anxiety-like behavior was assessed using the elevated plus maze, open field test, and light–dark box test, while biochemical and neurochemical investigations included estimation of malondialdehyde, glutathione, superoxide dismutase, catalase, corticosterone, inflammatory cytokines, monoamine neurotransmitters, GABA, brain-derived neurotrophic factor, tropomyosin receptor kinase B, and glial fibrillary acidic protein.
Results: The clozapine liqui-solid formulation significantly improved behavioral performance by increasing open-arm exploration, central-zone activity, and time spent in the light compartment compared with the caffeine-treated negative control group. Treatment also reduced lipid peroxidation, corticosterone, and pro-inflammatory cytokines, restored endogenous antioxidant defenses, normalized serotonin, dopamine, noradrenaline, and GABA levels, enhanced BDNF and TrkB expression, and reduced GFAP levels.
Conclusion: These findings demonstrate that the clozapine liqui-solid formulation exerts marked anxiolytic and neuroprotective effects through multi-mechanistic pathways involving behavioral modulation, antioxidant activity, anti-inflammatory action, neurotransmitter restoration, and neuroplasticity enhancement, suggesting that liqui-solid delivery may improve the therapeutic performance of clozapine in anxiety-related disorders.
Keywords: Anxiety; Clozapine; Liqui-solid formulation; Caffeine-induced anxiety; Wistar rats; Oxidative stress; Neuroinflammation; Neurotransmitters; BDNF; Neuroprotection.
How to cite this article: Rathore S, Patel J, Vengurlekar S, Jain SK. Anxiolytic and Neuroprotective Effects of a Clozapine Liqui-solid Formulation in a Caffeine-induced Anxiety Model in Wistar Rats. Int J Drug Deliv Technol. 2026;16(13s): 937-949. DOI: 10.25258/ijddt.16.13s.107.
Source of support: Nil.
Conflict of interest: None