Nanotechnology-Driven Delivery Systems for Antidepressants: Overcoming Blood–Brain Barrier Challenges

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Abstract
This chapter addresses the potential of nanotechnology to overcome one of the main barriers in the treatment of major depressive disorder (MDD), the blood–brain barrier (BBB), and the increased potential for drug delivery to the brain. Routine antidepressants have only been partially effective in treating depression because they do not easily cross the BBB, take too long to have an effect on patients, lack high bioavailability, and cause systemic side effects. In order to overcome these drawbacks, new nanotechnology-based drug delivery systems such as, liposomes, polymeric nanoparticles, dendrimers, nanoemulsions, and inorganic nanoparticles have been introduced. These nanocarriers increase the effectiveness of drug stability, controlled drug release, drug targeting, and brain bioavailability, while decreasing drug toxicity and off-target effects. This chapter also discusses the BBB structure, BBB drug delivery challenges, mechanisms of nanoparticle transport, and advanced targeting of the BBB through receptor-mediated delivery and PEGylation. Various recent advancements, including smart nanoparticles, artificial intelligence (AI)-enabled delivery systems, gene-based therapies, and personalized nanomedicine, are also discussed. Overall, nanotechnology offers a paradigm shift in how to overcome BBB barriers and enhance the safety, efficacy, and precision of antidepressant treatment in future clinical use.

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