Abstract:
:Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-60 reduces synthetic burden by achieving high hydroxyl surface density at low generation, which plays a key role in brain penetration and glia targeting of dendrimers in CNS disorders. Systemically administered PEGOL-60 crosses impaired CNS barriers and specifically targets activated microglia/macrophages at the injured site in diverse animal models for cerebral palsy, glioblastoma, and age-related macular degeneration, demonstrating its potential to overcome impaired blood-brain, blood-tumor-brain, and blood-retinal barriers and target key cells in the CNS. PEGOL-60 also exhibits powerful intrinsic anti-oxidant and anti-inflammatory effects in inflamed microglia in vitro. Therefore, PEGOL-60 is an effective vehicle to specifically deliver therapies to sites of CNS injury for enhanced therapeutic outcomes in a range of neuroinflammatory diseases.
journal_name
Sci Advjournal_title
Science advancesauthors
Sharma A,Sharma R,Zhang Z,Liaw K,Kambhampati SP,Porterfield JE,Lin KC,DeRidder LB,Kannan S,Kannan RMdoi
10.1126/sciadv.aay8514subject
Has Abstractpub_date
2020-01-22 00:00:00pages
eaay8514issue
4issn
2375-2548pii
aay8514journal_volume
6pub_type
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