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

Area of Science:

• Nanotechnology
• Pharmaceutical Sciences
• Pharmacology

Background:

• Agomelatine (AG) exhibits a unique antidepressant mechanism but suffers from low oral bioavailability (<5%) due to extensive first-pass hepatic metabolism.
• This limitation restricts its clinical efficacy and necessitates alternative drug delivery strategies.

Purpose of the Study:

• To develop and evaluate a rectal thermosensitive in situ gel formulation for biosynthesized Agomelatine-silver nanoparticles (AG-AgNPs).
• The goal was to enhance Agomelatine's bioavailability by bypassing hepatic first-pass metabolism.

Main Methods:

• Agomelatine-silver nanoparticles (AG-AgNPs) were synthesized using gum acacia, silver nitrate, and ascorbic acid.
• A rectal thermosensitive in situ gel was optimized using a 3^2 factorial design.
• Physicochemical properties, in vitro drug release, and in vivo bioavailability were assessed.

Main Results:

• Successful synthesis of spherical AG-AgNPs confirmed by UV-VIS, TEM, and XRD.
• The optimized gel exhibited favorable characteristics: 91.64% drug content, 26.63°C gelation temperature, pH 7.2, 36.98s gel strength, and 80.24% sustained release over 6 hours.
• In vivo studies demonstrated a 277.5% increase in relative bioavailability compared to oral Agomelatine tablets.

Conclusions:

• The developed AG-AgNP-loaded thermosensitive in situ gel shows significant potential for rectal drug delivery.
• This approach effectively bypasses first-pass metabolism, substantially improving Agomelatine's systemic bioavailability and therapeutic potential.