Harnessing Nanocarriers to Improve Psychiatric Treatment: Progress, Limitations, and Future Directions

Xiaoyan Ge,1 Lei Zhao,1 Xiaoyan Xing,1 Yanyun Hao,2,3 Zhiyue Zhang,4– 7 Guoping Sun1 1Department of Pharmacy, Qingdao Mental Health Center, Qingdao, People’s Republic of China; 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 4State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 6Shandong Key Laboratory of Targeted Drug Delivery and Advanced Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 7NMPA Center for Innovation and Research in Regulatory Science, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Zhiyue Zhang, Email Zhiyue.zhang@sdu.edu.cn Guoping Sun, Email Sung.p@163.comAbstract: To address clinical bottlenecks of traditional antipsychotic drugs, including delayed onset of action, significant peripheral side effects, and poor patient compliance, nanodelivery systems offer a feasible approach through their unique physicochemical properties to improve drug solubility, optimize in vivo transport, and enhance blood-brain barrier (BBB) penetration efficiency. This review focuses on the application potential and translational value of nanodelivery systems in psychiatric disorders. We systematically summarize recent advances in the construction strategies of mainstream nanocarriers, including lipid‑based, polymer‑based, inorganic nanomaterials, Metal-Organic Frameworks (MOFs), and Extracellular Vesicles (EVs), as well as commonly used nanoparticle preparation and characterization techniques. We briefly discuss key challenges facing nanoformulations, such as long‑term safety, large‑scale production, and batch‑to‑batch consistency, and highlight future directions driven by artificial intelligence and precision medicine. This review aims to provide insights for the rational design of nanodelivery systems for psychiatric disorders and to advance the development of precision psychiatry. Various nanoparticle structures, including spherical, cubic and other shapes, are shown converging towards a central nanoparticle. This central nanoparticle is depicted moving towards and crossing a barrier, representing the blood-brain barrier. After crossing, the nanoparticles are shown reaching the brain, indicated by a brain illustration. The process suggests targeting the brain for drug delivery, with arrows indicating the direction of movement from the nanoparticles to the brain. The diagram emphasizes the role of nanoparticles in crossing the blood-brain barrier to deliver drugs effectively to the brain.Diagram of drug delivery using nanoparticles crossing the blood-brain barrier to target the brain.Keywords: antipsychotics, psychiatric disorders, BBB, nanoformulations, drug delivery, lipid-based nanoparticles, polymer-based nanoparticles, inorganic nanomaterials, MOFs, EVs