Green Deep Eutectic Solvent-Enabled Polycaprolactone Nanoparticle Synthesis: Comparative study of Emulsification methods for Diclofenac Acid Delivery in Tumor Therapy

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

This study aimed to develop and characterize diclofenac acid-loaded polycaprolactone (PCL) nanoparticles using green solvents, and to compare two preparation methods-emulsification solvent evaporation/extraction and spontaneous emulsification solvent diffusion.

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

Both methods produced spherical nanoparticles with mean radii of 115.5±1.2nm (evaporation/extraction) and 103.7±2.0nm (spontaneous diffusion), and PDI values of 0.29±0.07 and 0.26±0.06, respectively. Zeta potentials were -12.1±1.6mV and -3.4 ±1.8mV. Encapsulation efficiencies exceeded 70%. In vitro release studies showed sustained release over 66 hours, with cumulative releases of 36.97% and 39.07%. Release kinetics best fit the Korsmeyer-Peppas model (R² > 0.96).

The study demonstrates the feasibility of using a green solvent for PCL nanoparticle preparation, yielding biocompatible, sustained-release diclofenac formulations. This approach offers a safer and environmentally friendly alternative for nanoparticle-based drug delivery systems