Targeted Drug Delivery Systems for Central Nervous System Therapies

Targeted drug delivery systems seek to surmount the protective barriers of the central nervous system (CNS) by transporting therapeutic agents directly to affected regions while minimising systemic exposure. The blood–brain barrier (BBB) presents a major obstacle, as its tight endothelial junctions and active efflux mechanisms prevent most molecules from entering the brain. Advances in nanotechnology have led to the development of liposomes, polymeric nanoparticles and hybrid nanocarriers functionalised with ligands such as peptides, antibodies or small molecules. These vehicles exploit receptor-mediated transcytosis, enhanced permeability at disease sites and cell-penetrating peptides to traverse the BBB and accumulate within neural tissue. Modulating surface charge, size and hydrophilicity—often through PEGylation—extends circulation half-life and reduces immunogenicity. Stimuli-responsive elements enable on-demand release in response to pH changes, enzyme activity or external fields. Pre-clinical models of glioblastoma, ischaemic stroke and neurodegenerative disorders demonstrate that targeted carriers can achieve higher local drug concentrations, improved efficacy and reduced off-target toxicity. Ongoing efforts focus on optimising ligand density, refining manufacturing processes for clinical scalability and integrating imaging agents for real-time monitoring, thereby paving the way for precision therapies in CNS disorders.

Research from Nature Portfolio

Receptor-targeted immunoliposomes directed at the transferrin receptor on brain endothelium have been shown to enhance association with endothelial cells and promote subsequent delivery of encapsulated cargo into the brain parenchyma, underscoring the potential of receptor-mediated strategies to increase CNS exposure. Separately, liposomes equipped with a transferrin-binding peptide (T7) and loaded with a neuroprotective agent demonstrated efficient BBB penetration in ischaemic stroke models, resulting in reduced infarct sizes and improved neurological outcomes. These studies highlight how peptide functionalisation can guide nanocarriers across the BBB and amplify therapeutic benefit in acute CNS injury.

Targeted Drug Delivery Systems for Central Nervous System Therapies publication trend

The graph below shows the total number of articles in targeted drug delivery systems for central nervous system therapies across all publications each year (not limited to Nature Index journals).

Technical terms

Blood–brain barrier (BBB): A specialised endothelial interface that regulates the exchange of molecules between the bloodstream and the CNS.

Liposome: A nanoscale, spherical vesicle composed of phospholipid bilayers used to encapsulate and deliver therapeutic compounds.

PEGylation: The process of attaching polyethylene glycol chains to nanoparticles to enhance stability, prolong circulation and reduce immunogenicity.

Transcytosis: A cellular transport mechanism in which molecules are shuttled across endothelial cells via vesicular trafficking.

Nanocarrier: A nanoparticle-based vehicle engineered to transport drugs or imaging agents to specific tissues or cells.

References

1. Recent advances in liposomes and peptide-based therapeutics for glioblastoma treatment. Journal of Controlled Release (2024).
2. Heparin interferes with the uptake of liposomes in glioma. International Journal of Pharmaceutics X (2023).
3. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma. Scientific Reports (2017).
4. Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system. Scientific Reports (2015).