Engineering Nanocarriers for Dopamine Stabilization and Targeted Brain Delivery: Mechanisms, Approaches and Translational Challenges.

摘要

Dopamine plays a central role in motor control, cognition, reward signaling, and neuroendocrine regulation, and its dysregulation is strongly associated with neurological disorders such as Parkinson's disease. However, conventional dopaminergic therapies remain limited by poor blood-brain barrier (BBB) penetration, rapid systemic metabolism, short half-life, peripheral toxicity, and dopamine oxidation-induced neurotoxicity. Nanomedicine-based drug delivery systems have emerged as promising strategies to overcome these limitations by enhancing dopamine stability, improving BBB transport, enabling controlled release, and facilitating targeted delivery to dopaminergic brain regions. This review comprehensively summarizes current advances in dopamine-targeted nanotherapeutics, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, dendrimers, inorganic nanoparticles, exosomes, and biomimetic vesicles. Particular emphasis is placed on the dual role of nanocarriers in both facilitating dopamine delivery and protecting dopamine from oxidative degradation and reactive oxygen species-associated toxicity. Among currently investigated platforms, polymeric nanoparticles, lipid-based nanocarriers, and exosome-inspired vesicles appear particularly promising due to their ability to improve dopamine stability, facilitate controlled release, enhance BBB penetration, and enable targeted brain delivery. The review additionally discusses receptor-mediated targeting strategies, intranasal delivery approaches, translational barriers, manufacturing scalability, long-term safety considerations, and regulatory challenges associated with clinical implementation. Finally, emerging future directions involving AI-assisted nanocarrier engineering, precision-targeted delivery systems, and stimuli-responsive nanomedicine are highlighted as promising approaches for the development of next-generation therapies for neurodegenerative disorders.