Mg–Al LDH/Tryptophan Nanoparticle System Improves Depressive-like Behavior in Rats

The COVID-19 pandemic has intensified global mental health issues, notably anxiety and depression. l-Tryptophan (TRP), a serotonin precursor, has shown promise as a nutritional intervention; however, its clinical application is limited by its poor bioavailability and low blood–brain barrier permeability. In this study, we developed a novel nanohybrid by intercalating TRP into magnesium–aluminum-layered double hydroxides (TRP-LDH) via coprecipitation. The basal reflection shifts and an interlayer space of 1.11 nm confirm the successful intercalation of tryptophan into the LDH structure. FTIR analysis revealed characteristic TRP bands, notably the N–H bending vibration at 1612 cm–1, supporting its incorporation into the LDH matrix. In vitro release in phosphate buffer (pH 7.4) demonstrated sustained TRP release for 48 h. From a mechanistic perspective, the LDH matrix likely enhances TRP bioavailability and brain delivery by protecting the amino acid from degradation and facilitating its diffusion across the blood–brain barrier, thus improving serotonergic modulation. In vivo behavioral tests in male Wistar rats (n = 8/group) revealed that TRP-LDH (94 mg/kg) significantly increased the struggling time and frequency and immobile frequency and time compared to control and TRP per se subjects in the forced swimming test, a standard model for antidepressant screening drugs, which suggests an antidepressant effect. These findings suggest TRP-LDH as a promising nanohybrid for mood disorder management.