Influence of green preparation methods on properties of polycaprolactone nanoparticles and effect of particles attributes on hydrogel specifications

As part of efforts to minimize the harmful effects of toxic solvents associated with the production of polymeric nanoparticles, polycaprolactone (PCL) nanoparticles were synthesized using three different methods: emulsification solvent evaporation/extraction, spontaneous emulsification solvent diffusion, and nanoprecipitation. In this study, and for the first time, Menthol/Camphor and Menthol/Camphor/Thymol—both green eutectic solvents—were successfully used to dissolve PCL and facilitate nanoparticle synthesis. Various formulation parameters, including temperature, polymer number average molecular weight and concentration, emulsifier type, solvent composition, internal-to-external phase ratio, and the addition of an extraction phase, were systematically evaluated for their impact on nanoparticle characteristics such as morphology, zeta potential, size, and size distribution. Furthermore, the effect of incorporating PCL nanoparticles into a hydrogel network was investigated. Selected formulations of PCL nanoparticles, with their diverse properties and concentrations, were embedded in a PVP/Chitosan/Poloxamer 407 hydrogel crosslinked via gamma irradiation. The successful incorporation of nanoparticles was confirmed through DSC and FTIR analyses. This study demonstrated that PCL nanoparticles enhance the structural integrity of the hydrogel, increase its hydrophobicity, and reduce the minimum gamma irradiation dose required for hydrogel formation. The resulting hydrogels exhibited a high gel fraction with favorable swelling behavior across different temperatures and pH conditions.