https://doi.org/10.1093/braincomms/fcad356. BRAIN COMMUNICATIONS 2024

Following the recent interest in oxidative stress in neurodegenerative disease and the possibility of using antioxidant therapy to reduce this kind of brain damage, further enhancements to SOD-2 drug delivery may advance its therapeutic uses.

Oxidative stress in the neuronal environment due to mitochondrial dysfunction may be alleviated by enhancing the superoxide dismutase (SOD-2) activity.

Delivering drugs to reduce oxidative stress and reactive oxygen species in the brain may be effective systemically, but crossing the BBB to reduce oxidative stress in the brain has considerable challenges.

The integrity of the blood-brain barrier (BBB) and CSF prevents external systemic materials from entering the brain extracellular fluid. This monolayer of endothelial capillary cells is packed tightly to inhibit the passage of toxins, pathogens and drugs that could damage the brain. This proves a considerable challenge for the administration of therapies for neurodegenerative disorders. Only small and lipophilic molecules can cross the BBB using passive diffusion or active transport, transcellular and paracellular.

SOD-2 can be encapsulated by lipid microparticles, which can protect the drug and enhance delivery through the BBB. They can also have attached ligands that can target specific receptors on the BBB.

Some unique olfactory anatomical features, and microvilli, provide a large surface area for the absorption of substances. This provides direct access to the brain. The intranasal high-density microvascular system enhances drug absorption and distribution. However, some limitations to delivery include rapid mucociliary clearance and the mucus layer, as well as some nasal enzymes that can inhibit drug absorption. These barriers to efficient intranasal drug delivery could be improved by the use of dissolving microneedles made of hyaluronic acid and a base of tannic acid-crosslinked gelatin, which can release drugs while avoiding microbial communities and without affecting the nasal cilia. This delivery system substantially attenuated H2O2-induced neurocyte damage in animal studies.

The recent development of SOD-2 lipid nanoparticles and versatile nanoparticulate systems is considered an interesting target for intranasal delivery of proteins, peptides and hormones to the brain.

Novel microneedle-mediated nanomedicine intranasal drug delivery may improve the delivery of neurodegenerative disease treatment, such as SOD-2 mimetics, to reduce oxidative stress in the pathogenesis of Alzheimer’s Disease.

References

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