Assessment of the Effect of an Organic Solvent on the Physicochemical Properties of Polymer Nanoparticles

Polymer nanoparticles are promising drug delivery systems that enable drug encapsulation. Their stability and safety depend on synthesis conditions, particularly the choice of organic solvent. This study evaluated the stability of polylactide-co-glycolide nanoparticles for peptide “Ipamorelin” delivery, synthesized using ethyl acetate, acetone, and dimethyl sulfoxide (DMSO). Nanoparticles were prepared by nanoprecipitation using polyvinyl alcohol as a stabilizer. Particle physicochemical characteristics were measured by dynamic light scattering 1 hour after preparation and after one week. All samples remained within the target size range of 100–250 nm. Nanoparticles synthesized with ethyl acetate and DMSO demonstrated multimodal size distributions of 164/190 nm and 190/220 nm, respectively. The acetone-based sample initially exhibited a monomodal distribution with a peak at 190 nm; after one week, a secondary peak at 164 nm appeared, potentially indicating the onset of degradation. The zeta potential of all systems remained between −15 and −5 mV, suggesting overall physical stability. The exception was the ethyl acetate sample, for which the zeta potential shifted from −13 to −7 mV. Overall, the solvent did not significantly affect particle size distribution or structural stability. However, solvent toxicity remains an important consideration. Acetone and ethyl acetate are more hazardous than DMSO, limiting their suitability for pharmaceutical applications. Therefore, material safety should take priority over minor differences in nanoparticle physicochemical properties.