A novel dual-action drug TJ94 facilitated by lipid nanocrystal formulations targeting neuroprotection and antithrombosis in ischemic stroke.

Platelet aggregation and neuronal injury are central factors underlying the pathogenesis of ischemic stroke (IS), thus dual-acting drugs possessing both antiplatelet and neuroprotective effects are highly needed. We synthesized a novel dual-action drug-TJ94 for neuroprotective and anti-platelet action in IS. To facilitate intravenous administration of TJ94, we developed a lipid nanocrystal formulation (TJ94@LNC) to increase the solubility, brain accumulation and therapeutic of TJ94 effects on IS. Our results clearly indicated that TJ94@LNC has great potential in brain accumulation due to the enrichment of transferrin (Tf) and apolipoprotein A1 (ApoA1) in the protein corona, which might improve the therapeutic effects of TJ94 on middle cerebral artery occlusion/reperfusion (MCAO/R) rats in both the acute and chronic phase of IS. Consistent with the design of TJ94, its therapeutic effects are attributed to its neuroprotective properties, which include inhibiting oxidative stress and apoptosis, as well as its antiplatelet activity. This lipid nanocrystal nanoplatform effectively addresses the brain delivery challenges of TJ94 to synergistically exert dual-functional therapeutic effects. It provides an effective solution for the intravenous injection of lipid-soluble drugs for the treatment of IS. This research presents TJ94@LNC as a promising therapeutic nanoplatform for IS.