Lipid–Polymer Hybrid Nanoparticles for Depression Therapy: A Novel Strategy for Enhanced Brain Drug Delivery

Abstract

the blood–brain barrier (BBB), poor drug bioavailability, and systemic side effects of conventional antidepressants. Nanotechnology-based drug delivery systems, particularly lipid–polymer hybrid nanoparticles (LPHNPs), have emerged as a promising approach to address these limitations. LPHNPs combine the advantages of both lipidic and polymeric nanocarriers—offering improved drug loading, stability, sustained release, and enhanced BBB penetration. This review highlights the current state of research on LPHNPs for antidepressant delivery, covering formulation strategies, physicochemical properties, targeting mechanisms, and in vitro/in vivo performance. The potential of LPHNPs to deliver selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), herbal bioactives, and neuroprotective agents directly to the brain is explored. Additionally, the challenges and regulatory perspectives for translating these hybrid systems into clinical therapies are discussed. Overall, LPHNPs represent a next-generation nanoplatform for targeted and effective treatment of depression.