Brain delivery of antidotes by polymeric nanoparticles

Abstract

Accidental intoxications from environmental pollutants, as well as intentional selfand chemical warfare-related poisonings affect millions of people worldwide each year. While many toxic agents can readily enter the central nervous system (CNS), the blood-brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. Consequently, poisoning antidotes usually cannot reach their site of action in the CNS in therapeutically relevant concentrations, and thus only provide effective protection to the peripheral nervous system. This limitation can be overcome by encapsulating the antidotes in nanoparticles (NP), which can enhance their CNS accumulation without damaging the integrity of the BBB. Among nanocarriers, polymerbased drug delivery systems exhibit remarkable benefits, such as bioavailability, cell uptake and tissue retention. Furthermore, due to their capacity to mask unfavorable physicochemical properties of cargo drugs, polymeric NPs were able to improve BBB transport of various pharmaceuticals. However, while polymer NP-mediated treatment of various pathological brain conditions, such as glioma and Alzheimer's disease were exhaustively studied, the application of polymeric nanocarriers for braintargeted delivery of antidote molecules has not been adequately examined. To display its therapeutic potential, we review the state of the art of polymer NP-assisted CNS delivery of antidotes for various poisonings, including heavy metal and organophosphorus intoxications.

Advances in nanotechnology for the treatment of GBM

“…To achieve high sensitivity, high specificity, high resolution and deep tissue penetration, researchers are actively developing a variety of imaging techniques and contrast agents (Tang et al, 2019). The small particle sizes of nanomaterials, which include natural or synthetic particles with diameters between 1 and 1,000 nm (Manek and Petroianu, 2021), endow them with an important advantage. In addition, nanoparticles can have properties that differ from those of traditional drugs, such as photosensitivity and magnetism.…”

A fast-acting brain-targeted nano-delivery system with ultra-simple structure for brain emergency poisoning rescue

“…brain cancers 1,2 and neurodegenerative diseases [3][4][5] ), and acute conditions (e.g. cerebral infarction 6 and poisoning 7 ). Over past decades, increasingly more brain-targeted nano delivery systems (BTNDS) have been developed [8][9][10][11] to allow drugs to cross the BBB for the treatment of brain diseases.…”

Brain-targeted nanoreactors prevent the development of organophosphate-induced delayed neurological damage

“…These classical medical countermeasures mitigate acute toxicity effects but have limited effects on OP-induced irreversible brain damage due to their poor penetration across the BBB. Thus, there have been active attempts to improve brain-targeted nano delivery systems loaded with conventional drugs to prevent CNS damage by OPs [ 19 , 20 ]. To date, a variety of nanoparticles (NPs) with unique physicochemical properties have been tailored as brain‐targeted nano delivery systems, especially when functionalized with specific targeting ligands.…”