Brain targeted drug delivery using liposomes and polymeric nanocarriers: Pharmaceutical and preclinical perspectives in Alzheimer's and Parkinson's disease

The treatment of Alzheimer's disease (AD) and Parkinson's disease (PD) has remained a major clinical challenge because these disorders are biologically complex, exhibit inter-patient variability, are often diagnosed late, involve irreversible neurodegeneration, and face limitations due to the blood-brain barrier (BBB). The presence of the BBB is one of the most critical obstacles in AD and PD therapy, hindering the potential to elevate their treatment to a new level. To do so, nanotechnology has introduced the design of nanomedicine-based delivery systems that optimize pharmacokinetics and enhance brain exposure across the BBB. Additionally, many promising agents, such as peptides, proteins, small interfering RNA (siRNA), antioxidants, anti-inflammatory compounds, neurotrophic factors, and small molecules with poor solubility, have failed due to instability, toxicity, or poor pharmacokinetics. Thus, delivery systems can protect them from enzymatic degradation, improve solubility and stability, and enable controlled release. Among the diverse array of nanocarriers studied, liposomes and polymeric nanoparticles have received significant attention. They can be surface functionalized with targeting ligands and designed to exploit receptor-mediated transcytosis, leading to selective and enhanced brain targeting while reducing systemic exposure. Their ability to incorporate both hydrophobic and hydrophilic compounds allows for flexible formulation design and supports targeted delivery strategies that reduce off-target toxicity. They offer biocompatibility, adjustable physicochemical characteristics, and significant potential for targeted brain delivery. Accordingly, this review focuses on liposomal and polymeric nanoparticle-based delivery systems, critically assessing their pharmaceutical design and preclinical performance to identify translational gaps and highlight emerging strategies for effective brain-targeted therapies in AD and PD.