Nanotechnology in Neuroprotection: Mechanistic Opportunities, Delivery Constraints and Translational Priorities

2026-10-22T13:22:17+00:00

Nanotechnology is increasingly used to alter the pharmacokinetics, cellular distribution and biological activity of putative neuroprotective agents, yet enhanced brain delivery should not be equated automatically with neuroprotection. This critical narrative review evaluates nanotechnology-enabled neuroprotection across the blood-brain barrier and neurovascular unit, with emphasis on whether platform design produces credible neuronal preservation rather than only improved uptake. Literature published from 2005 to 8 August 2026 was considered, together with earlier foundational work when necessary, using live searches of biomedical and multidisciplinary scholarly sources and citation-based verification. The synthesis focuses on lipid and polymeric nanocarriers, dendrimers, inorganic nanozymes, biomimetic systems and intranasal approaches, and compares evidence across Alzheimer disease, Parkinson disease, ischaemic stroke, traumatic brain injury and selected inflammatory or developmental central nervous system injuries. Preclinical evidence is most persuasive when carrier behaviour, target engagement and a defined injury mechanism converge, as illustrated by catalytic antioxidant nanomaterials, glia-targeted anti-inflammatory dendrimers and nanoparticle strategies directed at secondary injury cascades. In chronic neurodegeneration, by contrast, improvements in biodistribution or molecular target engagement frequently outpace evidence for durable disease modification. Disease-dependent blood-brain barrier dysfunction, protein-corona formation, cell-specific uptake, nanoparticle persistence, neurotoxicity, route-dependent exposure and manufacturing variability remain major sources of uncertainty. The translational problem is therefore not simply how to cross the blood-brain barrier, but how to achieve reproducible exposure in the relevant brain compartment at the relevant disease stage while preserving safety and demonstrating meaningful functional benefit. Progress will depend on human-relevant barrier models, quantitative biodistribution and target-engagement standards, chronic safety studies, scalable chemistry and manufacturing controls, and clinically aligned outcome selection. Nanotechnology is best viewed as an enabling framework for neuroprotection rather than an intrinsically neuroprotective class of therapy.

Journal of Pharmaceutical Research International

Nanotechnology in Neuroprotection: Mechanistic Opportunities, Delivery Constraints and Translational Priorities