PEGylated Chitosan Biodegradable Nanoparticles Delivery of Salvia officinalis and Melissa officinalis for Enhanced Brain Targeting

Background: Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by the gradual decline of cognitive abilities, primarily caused by impairments in the cholinergic system. AD is diagnosed based on the presence of specific pathological features, including senile plaques, neurofibrillary tangles, and the loss of neurons and synapses. Despite ongoing efforts, the etiology of AD remains unclear, and there is a significant lack of effective treatments to meet the medical needs of affected individuals. The complex nature of AD, involving multiple factors, presents challenges in the development of potential therapies. Numerous obstacles hinder the achievement of optimal pharmacological concentration of promising molecules for AD treatment. These obstacles include the presence of the blood-brain barrier (BBB), which restricts the entry of therapeutic agents into the brain, as well as issues related to poor bioavailability and unfavorable pharmacokinetic profiles. Unfortunately, many therapeutically promising compounds have failed to overcome these hurdles and demonstrate efficacy in treating AD. Methods: The PEGylated chitosan nanoconjugate was developed and evaluated for delivery of anti-Alzheimer natural extract of Salvia officinalis and Melissa officinalis to the brain. The nanoconjugates (S-PCN and M-PCN) were developed by ionic gelation technique. Result: The nanoconjugates (S-PCN and M-PCN) were evaluated for various optical and in-vitro parameters. MTT assay on UCSD229i-SAD1-1 human astrocytoma cells indicated IC50 values of 0.42, 0.49, 0.67, and 0.75 μM for S-PCN, M-PCN formulations, and free Salvia officinalis and Melissa officinalis extracts, respectively. The In vitro assessments using cell lines have confirmed the improved uptake and distribution of nanoconjugates compared to free extracts. These findings were validated through confocal microscopy and apoptosis assays, revealing a substantial increase in the accumulation of nanoconjugates within the brain. The targeting potential OF M-PCN over S-PCN was found to be 2-fold significant. Conclusion: Based on the findings, it can be inferred that biodegradable PEGylated chitosan nanoconjugates hold promise as effective nano-targeting agents for delivering anti-Alzheimer drugs to the brain. The incorporation of PEGylated chitosan nanoparticles in this approach demonstrates enhanced delivery capabilities, ultimately leading to improved therapeutic outcomes.