Targeting Alzheimer’s disease pathology: influence of nano-based drug delivery systems loaded with a combination of herbal and synthetic drugs.

Alzheimer's Disease (AD) is a progressive neurological disordermarked by cognitive decline and memory loss. Current treatments,including acetylcholinesterase inhibitors (AChEIs) and NMDA receptorantagonists, provide only symptomatic relief due to poor Blood BrainBarrier (BBB) permeability and side effects. The integration ofsynthetic and natural drug combinations with nanotechnology offers apromising strategy to enhance drug delivery, efficacy, and overalltherapeutic outcomes. This review explores the integration of herbal and synthetic drugs innano-based delivery systems for AD treatment. It examines co-loadingefficiency, release kinetics, and synergistic therapeutic benefits ofdual-drug formulations. Additionally, it discusses target-specificligand functionalization for improved BBB penetration and neuronaltargeting, alongside a comparative analysis of dual- vs. single-drugformulations and their impact on diseaseprogression and efficacy. Current treatment options primarily offer symptomatic relief in theirearly stages, while failing to target the multiple neurobiologicalmechanisms responsible for AD progression. In light of this,combining the already established treatments with herbal drugs, wecan leverage their combined effects to enhance treatment efficacy andmitigate side effects. Furthermore, co-loading of synthetic drugs andphytoconstituents within a single nanoformulation can improvesite-specific drug delivery, offer sustained release, and lowersystemic side effects, resulting in better treatment outcomes.