Green solvent-based synthesis of diclofenac diethylamine-loaded PCL nanoparticles for sustained drug delivery

Abstract

Background

Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), has demonstrated promising antitumor properties; however, its clinical application is limited by systemic toxicity. Encapsulation in biodegradable polymeric nanoparticles offers a strategy to enhance therapeutic efficacy while minimizing adverse effects. Nevertheless, the use of toxic organic solvents in nanoparticle fabrication remains a significant challenge.

Objective

This study aimed to develop and characterize diclofenac diethylamine-loaded polycaprolactone (PCL) nanoparticles using green solvents and to compare two preparation methods-emulsification solvent evaporation/extraction and spontaneous emulsification solvent diffusion-for producing diclofenac-loaded nanoparticles with potential applications in tumor therapy.

Methods

Diclofenac diethylamine-loaded PCL nanoparticles were prepared using both methods, employing a novel green solvent system. The nanoparticles were characterized in terms of size, polydispersity index (PDI), zeta potential, morphology, and encapsulation efficiency. In vitro drug release profiles were evaluated and fitted to kinetic models.

Results

The developed diclofenac diethylamine-loaded PCL nanoparticles exhibited a mean diameter below 200 nm, a monodisperse population, and a negative surface charge. Both preparation methods achieved high encapsulation efficiency and prolonged, diffusion-controlled drug release. The spontaneous solvent diffusion method provided slightly better control over particle size.

Conclusion

These nanoparticles are well-suited for cancer therapy, offering sustained drug release, enhanced safety due to the use of green solvents, and robust physicochemical stability. The findings support their potential as an innovative, effective, and safe delivery system for antitumoral applications.