Development of Ergosterol Nanoliposome-based Delivery System Pertaining Toxicity Evaluation and Therapeutic Potential for Alzheimer’s Disease

Introduction: Alzheimer’s disease (AD), a debilitating neurodegenerative disorder, presents a growing global health challenge due to limited therapeutic options. Ergosterol, known for its neuroprotective and antioxidant properties, suffers from poor bioavailability. This study aimed to develop ergosterol-loaded nanoliposomes (ER-NL-2) and evaluate their safety, antioxidant potential, and therapeutic efficacy in animal models of AD. Methods: ER-NL-2 was formulated using the ultrasonic thin-film dispersion method and characterized via dynamic light scattering (DLS), zeta potential, and TEM. Acute oral toxicity was assessed in Wistar rats and Swiss mice (2000 mg/kg). Two AD models were employed: Streptozotocin (STZ)- induced in Swiss albino mice and AlCl₃-induced in Wistar albino rats. Behavioral studies included actophotometer and elevated plus maze tests. Antioxidant assays measured SOD, CAT, GSH, and LPO levels. Histopathological analysis of brain tissue was conducted. Results: ER-NL-2 exhibited a mean droplet size of ~180 nm, PDI <0.3, and zeta potential of -27.9 mV. TEM confirmed spherical morphology. Toxicity studies showed no abnormalities. In both AD models, ER-NL-2 improved locomotor activity and reduced transfer latency. Biochemical analyses revealed elevated SOD, CAT, GSH and reduced LPO levels. Histopathology showed preserved neuronal integrity and reduced neurofibrillary tangles in treated groups. Discussion: ER-NL-2 demonstrated neuroprotective efficacy through behavioral, biochemical, and histological endpoints, confirming its antioxidative mechanism and brain safety profile. It was comparable to standard therapy (donepezil). result: Mean droplet size was 200 nm, with a PDI around 0.3, indicating a homogeneous distribution. Zeta potential (-27.9mV) ensured particle stability, while TEM confirmed spherical nanoscale particles. No mortality or toxicity signs were observed in acute oral toxicity studies. Histopathological analysis of the kidney, liver, stomach, and brain revealed no abnormalities, demonstrating the formulation's safety. ER-NL-2 significantly improved locomotion and reduced transfer latency in STZ and AlCl₃-induced Alzheimer’s models compared to control groups, indicating enhanced cognitive and motor function. Treated groups showed increased SOD, CAT, and GSH levels while reducing LPO levels compared to controls, highlighting potent antioxidative activity. Histopathological studies showed preservation of neuronal structure and reduction in neurofibrillary tangles and inflammation in treated groups compared to controls. Conclusion: ER-NL-2 is a safe and promising nanocarrier for Alzheimer’s treatment with significant neuroprotective and antioxidant properties. Further studies are warranted to explore its pharmacokinetics and clinical applicability.