Nanoplatforms for Anxiety Therapy: A Review of Cellular, Animal, and Clinical Studies

Resumo

Abstract: Anxiety disorders are among the most prevalent psychiatric conditions, imposing substantial individual and societal burdens. Their pathogenesis involves a complex interplay of neurobiological alterations, including neurotransmitter imbalances, neuroinflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and oxidative stress. Despite the availability of anxiolytic medications, limitations such as delayed onset of action, suboptimal efficacy, and significant side effects underscore the need for novel therapeutic strategies. Nanoparticles, as advanced drug delivery systems capable of crossing the blood–brain barrier and selectively targeting neural networks, offer promising avenues for the treatment of anxiety disorders. This review aims to examine the therapeutic applications of nanoparticles in anxiety and to elucidate the underlying neurobiological mechanisms. A narrative-analytical review was conducted through a systematic search of PubMed, Scopus, and Web of Science databases from 2010 to 2025. Key terms were selected based on Medical Subject Headings (MeSH) and included “anxiety,” “nanoparticles,” “targeted drug delivery,” “neuroinflammation,” and “blood–brain barrier.” Eligible studies encompassed preclinical research, animal models, and relevant review articles. Data were extracted qualitatively and thematically analyzed. Evidence indicates that nanocarriers such as chitosan, poly (lactic-co-glycolic acid) (PLGA), zinc oxide nanoparticles, and brain-targeted formulations can enhance blood–brain barrier penetration, improve bioavailability, and attenuate oxidative stress, thereby reducing anxiety-like behaviors and improving cognitive function. Conversely, exposure to certain nanoparticles including silica, polystyrene, silver nanoparticles, and specific inorganic particles has been associated with mitochondrial dysfunction, neuroinflammation, gut–brain axis dysregulation, and hippocampal injury, potentially exacerbating anxiety- and depression-like behaviors. These findings underscore the critical influence of nanoparticle type, dose, size, and surface properties on their biological effects. Nanoparticles and nanocarrier-based drug delivery systems hold significant potential to advance targeted therapy for anxiety disorders through modulation of neuroendocrine pathways, reduction of neuroinflammation, and enhancement of cognitive performance. Nevertheless, concerns regarding potential neurotoxicity and long-term effects highlight the necessity for rigorous preclinical evaluation and standardized clinical trials to ensure safety and therapeutic efficacy.