Abstract

Background: Obesity, considered a complex condition, is the fastest-growing public health concern worldwide. Its treatment is limited due to the side effects of pharmacological options available, outweighing their benefits.

Aim: The present study aims to formulate a novel biodegradable formulation of exenatide for direct brain delivery through the nasal route.

Methods: To formulate exenatide loaded poly (lactide-co-glycolide) (PLGA) nanoparticles, a double emulsion (w/o/w) solvent evaporation method was employed. A full factorial (33) design of the experiment was used to optimize the formulation.

Results: The entrapment efficiency and particle size of the optimized formulation were found to be 68% and 110 nm, respectively. The in-vitro drug release study indicated the sustained release of 48% drug in 5 days. The safety of drug-loaded PLGA nanoparticles for intranasal delivery was indicated by the sheep nasal toxicity study. The efficacy of the developed nanoparticles was demonstrated by an in-vivo pharmacodynamics study on Albino Wistar rats, showing a 6.2% weight reduction after 30 days of treatment.

Conclusion: Thus, exenatide is a novel peptide having significant weight loss benefits and no severe side effects. Long-term studies in at least two or more animal models followed by extensive clinical evaluation can safely result in a product for clinical use.

Keywords: Obesity, exenatide, PLGA nanoparticles, double emulsification solvent evaporation, sheep nasal toxicity study, in vivo pharmacodynamic study.