Rectal In Situ Thermosensitive Gel Loaded with Agomelatine-Silver Nanoparticles: Formulation and Characterization

Agomelatine (AG) is a novel antidepressant characterized by distinct mechanism of action and minimal side effects. However, extensive first-pass hepatic metabolism limits its clinical efficacy after oral administration, leading to low bioavailability (<5%). To get around these restrictions, the current study set out to create and assess a rectal thermosensitive in situ gel using biosynthesized AG-silver nanoparticles (AG-AgNPs). AG-AgNPs were successfully synthesized with gum acacia as a stabilizing agent, using silver nitrate as a precursor, and ascorbic acid as a reducing agent. The in situ gel formulation was optimized using a 3² factorial design, and then physicochemical, in vitro, and in vivo assessments were conducted. Nanoparticle formation was also evidenced by the appearance of a visible color change, UV-VIS, TEM, and XRD analysis techniques, which depicted spherical-shaped nanoparticles and a crystalline nature. The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine.