Characterization of Polymer Nanoparticles: An Educational Case Based on PEO–PCL Self-Assemblies Illustrating the Pitfalls to be Avoided

Although polymer nanoparticles for drug delivery are routinely described, their thorough characterization is often overlooked. Two systems containing self-assemblies of poly(ethylene oxide)-<i>block</i>-poly(ε-caprolactone) (PEO-PCL) copolymers are presented to illustrate the extreme caution with which they must be characterized: PEO-PCL 5000-4000 g·mol^-1 yielded a single population of micelles, while PEO-PCL 2000-7000 g·mol^-1 formed a mixture of micelles, vesicles, and wormlike objects. Both were initially characterized by single-angle dynamic light scattering (DLS) and transmission electron microscopy (TEM), as is standard practice. The analysis of the PEO-PCL 5000-4000 micelles demonstrated the relevance of these techniques in such a case. However, while DLS indicated a single population for PEO-PCL 2000-7000, TEM images revealed a mixture of morphologies. Complementary cryo-TEM imaging and multiangle dynamic and static light scattering analyses provided essential information for an improved characterization. Based on these examples, this article offers recommendations for the reliable characterization of polymer nanoparticles.