Critical assessment of purification processes for the robust production of polymeric nanomedicine

Polymeric nanoparticles are among the most widely used nanocarriers for delivering therapeutic molecules. However, their synthesis processes often generate undesirable impurities that could be toxic and challenging to eliminate. In this study, we compared three purification techniques - centrifugation, dialysis, and tangential flow filtration (TFF) - to evaluate their efficacy in removing residual drug, surfactant, and solvent while preserving the nanoparticles' physicochemical features (hydrodynamic size, zeta potential, polydispersity index). Centrifugation excels in eliminating unencapsulated drug and residual surfactant but significantly affects the nanoparticles' physicochemical properties, such as colloidal stability and size homogeneity. On the other hand, dialysis is a gentler technique effective in removing residual solvent but less so for residual surfactant and unencapsulated drug. TFF emerges as a balanced approach, offering a compromise between the two but none of these techniques achieves satisfactory purification at lab-scale alone. While each technique has its merits, none can meet all requirements independently. The optimal purification strategy often involves a combination of techniques, determined on a case-by-case basis considering factors like purity levels, time, costs, and the preservation of critical properties such as drug loading and colloidal stability. This study underscores the need for a nuanced approach in selecting purification strategies for polymeric nanoparticles in drug delivery applications.