Cyclodextrin-Based Drug Delivery Systems for Depression: Improving Antidepressant Bioavailability and Targeted Central Nervous System Delivery.

Cyclodextrin (CD)-based drug delivery systems have emerged as a promising strategy to overcome limitations commonly encountered in antidepressant therapy, including low bioavailability, poor solubility, and suboptimal penetration of the blood-brain barrier. This review synthesizes current evidence demonstrating that complexing various classes of antidepressants-such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants-with β-CD or its derivatives significantly enhances drug solubility and stability. In addition, encapsulation with CDs can diminish systemic toxicity and improve pharmacokinetics, thereby helping to optimize dosage regimens and reduce adverse effects. Analysis of published in vitro and in vivo studies indicates that CD formulations not only boost therapeutic efficacy but also enable sustained or targeted release, which is critical for drugs requiring precise plasma and tissue concentrations. When compared to other carriers (e.g., liposomes, polymeric nanoparticles, dendrimers), CD-based systems often stand out for their ease of formulation, biocompatibility, and cost-effectiveness, although limited drug-loading capacity can be a drawback. We recommend expanding in vivo trials to substantiate the clinical benefits of CD-antidepressant complexes, particularly for treatment-resistant cases or specific subpopulations (e.g., elderly and pediatric patients). Additional investigations should also explore hybrid systems-combining CDs with advanced nano- or macroparticles-to amplify their advantages and address any limitations. Ultimately, integrating CDs into antidepressant regimens holds substantial potential to refine therapy outcomes, reduce adverse events, and pave the way for more personalized, effective interventions for depression.