Nanoparticle-Based Drug Delivery in Neurological Disorders

Neurological disorders such as Alzheimer’s and Parkinson’s disease, stroke and brain tumours remain leading causes of morbidity worldwide. The blood-brain barrier (BBB) imposes a formidable obstacle to systemic therapies, restricting passage of most small molecules and nearly all macromolecules. Nanoparticle-based delivery systems overcome these limitations by exploiting tailored physicochemical properties—size, surface charge, hydrophobicity and ligand decoration—to traverse or transiently modulate the BBB. Lipid-based vehicles (liposomes, nanoemulsions), polymeric constructs (PLGA, polyethylene glycol conjugates, dendrimers) and inorganic frameworks (metal-organic frameworks, silica or metallic nanoparticles) have each been engineered for enhanced permeability, prolonged circulation and targeted cellular uptake. Such platforms enable precise loading and controlled release of neuroprotective agents, anti-inflammatory drugs, growth factors or genetic material, often with real-time imaging capabilities. Recent advances include stimuli-responsive carriers that release cargo in response to pH, redox potential or enzymatic activity in diseased tissue. Together, these innovations promise to improve therapeutic indices, reduce systemic toxicity and open new horizons for precision medicine in central nervous system disorders.

Research from Nature Portfolio

Engineered chiral metal-organic frameworks incorporating ultra-small platinum nanozymes have demonstrated stereoselective blood-brain barrier transcytosis and potent anti-neuroinflammatory effects in Parkinsonian models. D-chiral frameworks achieved higher brain accumulation via multiple endocytic pathways, suppressing neuronal apoptosis and ferroptosis more effectively than their L-chiral counterparts, and thereby mitigating motor deficits and pathological hallmarks of disease.

Albumin-coated PLGA nanoparticles loaded with dopamine offer a non-invasive approach to replenishing nigrostriatal dopamine in a rodent model of Parkinson’s disease. These nanosystems readily crossed the blood-brain barrier, restored motor coordination and sensorimotor function to levels comparable with healthy controls, and afforded sustained neurotransmitter delivery with reduced systemic dosing.

Nanoparticle-Based Drug Delivery in Neurological Disorders publication trend

The graph below shows the total number of articles in nanoparticle-based drug delivery in neurological disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Blood-brain barrier (BBB): A selective endothelial barrier that restricts passage of substances from the bloodstream into the central nervous system.

Metal-organic framework (MOF): A porous crystalline network constructed from metal ions and organic linkers, used here as a scaffold for embedding catalytic nanozymes.

Nanozyme: A nanoparticle with enzyme-like catalytic activity, capable of scavenging reactive oxygen species or modulating biochemical pathways.

Liposome: A spherical vesicle composed of one or more phospholipid bilayers, used to encapsulate hydrophilic or hydrophobic drugs.

PLGA (poly(lactic-co-glycolic acid)): A biodegradable copolymer commonly used to fabricate nanoparticles for sustained drug release.

Theranostics: Integrated therapeutic and diagnostic functions within a single nanosystem, enabling both treatment and monitoring of disease.

Polymeric nanoparticle: A nanoscale particle formed from polymers that can be engineered for controlled drug release and targeted delivery to specific cells or tissues.

References

1. Chiral metal-organic frameworks incorporating nanozymes as neuroinflammation inhibitors for managing Parkinson’s disease. Nature Communications (2023).
2. Dopamine-loaded nanoparticle systems circumvent the blood–brain barrier restoring motor function in mouse model for Parkinson’s Disease. Scientific Reports (2021).
3. Hybrid nanostructures for neurodegenerative disease theranostics: the art in the combination of biomembrane and non-biomembrane nanostructures. Translational Neurodegeneration (2024).
4. Applications of Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders. Materials (2022).
5. An Insight to Brain Targeting Utilizing Polymeric Nanoparticles: Effective Treatment Modalities for Neurological Disorders and Brain Tumor. Frontiers in Bioengineering and Biotechnology (2022).