IN VIVO ANALYSIS OF BETULINIC ACID-LOADED CHITOSAN NANOPARTICLES FOR ALZHEIMER’S DISEASE TREATMENT

Abstract

Alzheimer’s disease is a progressive neurodegenerative disorder associated with oxidative stress, neuronal damage, and cognitive decline. Betulinic acid possesses neuroprotective and antioxidant properties; however, its poor solubility limits therapeutic efficacy. This study focuses on developing chitosan-based nanoparticles to enhance its delivery. To synthesize and evaluate betulinic acid chitosan nanoparticles (BA-C-NPs) for neuroprotective efficacy and safety in an in vivo Alzheimer’s disease model. BA-C-NPs were prepared using ionic gelation with chitosan (0.15–0.5% w/v) and TPP (0.07 0.75% w/v). Particle size (100–300 nm) and morphology were characterized using FE-SEM and HR-TEM. Acute toxicity was assessed at 2000 mg/kg in rats. Alzheimer’s disease was induced using scopolamine (1 mg/kg, i.p.). Animals were divided into control, disease control, Donepezil-treated, and BA-C-NPs-treated groups. Biochemical parameters, hematological indices, and histopathology were evaluated. BA-C-NPs showed no toxicity at 2000 mg/kg. Disease control animals exhibited reduced body weight (~125 g), haemoglobin (~11 mg/dL), RBC (~4.9 ×10⁶/mL), and increased SGOT (~225 U/L) and SGPT (~115 U/L). BA-C-NPs treatment improved body weight (~178 g), haemoglobin (~14 mg/dL), RBC (~5.6 ×10⁶/mL), and reduced SGOT (~180 U/L) and SGPT (~50 U/L). Histopathology showed reduced neuronal degeneration and improved brain architecture.    BA-C-NPs    demonstrated    significant    neuroprotective, antioxidant, and hepatoprotective effects with good safety profile, indicating their potential as an effective therapeutic strategy for Alzheimer’s disease.