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Antibody-Targeted Liposomes for Enhanced Targeting of the Blood-Brain Barrier.

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The blood-brain barrier (BBB) hinders therapeutic delivery to the central nervous system (CNS), thereby impeding the development of therapies for brain injury and disease. Receptor-mediated transcytosis (RMT) systems are a… Click to show full abstract

The blood-brain barrier (BBB) hinders therapeutic delivery to the central nervous system (CNS), thereby impeding the development of therapies for brain injury and disease. Receptor-mediated transcytosis (RMT) systems are a promising way to shuttle a targeted therapeutic into the brain. Here, we developed and evaluated an RMT antibody-targeted liposomal system. A previously identified antibody, scFv46.1, that binds to the human and murine BBB and can pass through the murine BBB by transcytosis after intravenous injection was used to decorate the surface of liposomes. Using an in vitro BBB model, we demonstrated the cellular uptake of scFv46.1-modified liposomes (46.1-Lipo). Next, the biodistribution and brain uptake capacity of 46.1-targeted liposomes were assessed after intravenous administration. Our results showed that 46.1-Lipo can lead to increased brain accumulation through targeting of the brain vasculature. Initial rate pharmacokinetic experiments and biodistribution analyses indicated that 46.1-Lipo loaded with pralidoxime exhibited a 10-fold increase in brain accumulation compared with a mock-targeted liposomal group, and this increased accumulation was brain-specific. These studies indicate the potential of this 46.1-Lipo system as a synthetic vehicle for the targeted transport of therapeutic molecules into the CNS.

Keywords: targeted liposomes; blood brain; antibody; brain barrier; antibody targeted; brain

Journal Title: Pharmaceutical research
Year Published: 2022

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