Vinpocetine-mediated multidimensional active targeted delivery across the blood-brain barrier.

Overcoming the challenges associated with brain-targeted drug delivery involves addressing both the limited biodistribution of drugs and microcirculation issues that hinder their accumulation in brain lesions. In this study, we propose a comprehensive strategy leveraging vinpocetine, a compound known to enhance cerebral blood flow (CBF), to improve drug delivery to the brain. Initially, the pre-administration of vinpocetine in the form of a microemulsion significantly enhances nanomedicine uptake into the brain by selectively boosting CBF. This creates a more favorable environment for drug distribution while also mitigating chemotherapy-induced cerebrovascular accidents. Building upon this, the use of vinpocetine as a targeting ligand for liposomes or lipid nanoparticles, compared to typical brain-targeting ligands (GSH, Apamin, and Angiopep-2), not only significantly improves drug distribution in the brain but also selectively targets glioma regions and maintains excellent immunocompatibility. Expanding on these findings, the direct conjugation of vinpocetine with therapeutic compounds leads to superior brain accumulation and enhanced antitumor efficacy, thereby extending its therapeutic potential. These results highlight the broad applicability of vinpocetine-based strategies for achieving efficient and precise brain-targeted drug delivery, offering promising prospects for treating a range of central nervous system disorders.