Self-Assembled Fingolimod (FTY720)-Loaded Polymeric Micelles Protect Brain from Injury in Intracerebral Hemorrhage

Polymeric micelles, originating from the self-assembly of amphiphilic block copolymers, presenting a lipophilic core and hydrophilic shell, are widely used as nanoscale drug-delivery systems. In the present study, the functional nanosized FTY720-loaded polymeric micelles (NP@FTY720) were constructed via covalent attachment of the terminal carboxy group of poly(ethylene glycol) (PEG) with FTY720 through an amide bond linker. FTY720 was embedded into the PEG core, which ensures high stability of the nanoparticle and significantly reduces nonspecific protein adsorption. The micellar system was characterized by good stability in a neutral environment and effective drug release in the lysosomal environment within cells. This enables NP@FTY720 to promote microglial M1 to M2 polarization in H₂O₂-induced BV2 microglia without apparent toxicity in vitro. Importantly, NP@FTY720 through intravenous administration accumulated at hemorrhagic sites and responsively released therapeutic FTY720 to exert neuroprotective roles following ICH in mice, which was involved in microglial M2 polarization and inflammation reduction. Taken in concert, our results suggest that the self-assembled FTY720-loaded polymeric micelles may represent a promising nanoformulation for intracerebral hemorrhage (ICH) treatment.