Characterization of Poly(methyl methacrylate) Nanoparticles Prepared by Nanoprecipitation Using Analytical Ultracentrifugation, Dynamic Light Scattering, and Scanning Electron Microscopy IGOR PEREVYAZKO, 1 ANTJE VOLLRATH, 1 STEPHANIE HORNIG, 1 GEORGES M. PAVLOV, 1,2,3 ULRICH S. SCHUBERT 1,2 1 Laboratory of Organic and Macromolecular Chemistry, Friedrich-Schiller-University Jena, Humboldtstrasse 10, 07743 Jena, Germany 2 Laboratory of Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands 3 Department of Physics, St. Petersburg University, Ulianovskaya Strasse 1, 198504 St. Petersburg, Russia Received 8 March 2010; accepted 25 May 2010 DOI: 10.1002/pola.24157 Published online in Wiley Online Library (wileyonlinelibrary.com). ABSTRACT: Nanoprecipitation represents an effective method for the production of polymeric nanoparticles. This technique was used to prepare nanoparticles from solutions of poly- (methyl methacrylate) and its copolymers. Since the regulation of main parameters like particle size, particle size distribution, and molar particle mass is very important for future applica- tions, the stable nanoparticle dispersions were examined by scanning electron microscopy, velocity sedimentation, and dynamic light scattering, whereby advantages and disadvan- tages of each characterization techniques are discussed. Poly- dispersities of particle size distributions are determined by the ratio of d w /d n , where d w and d n are weight- and number-aver- age diameters, respectively. The particle characteristics strongly depend on the chemical structure of the polymers and the way of preparation and, therefore, vary in the studied cases in the range of 6 < d w < 680 nm, whereas the polydispersity index d w /d n changes in the range of 1.02 to 1.40. It is shown that nanoparticles in a desirable size range can be prepared by solvent–nonsolvent methods (dialysis technique or dropping technique). V C 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3924–3931, 2010 KEYWORDS: dynamic light scattering; nanoparticles; SEM; ultra- centrifugation; velocity sedimentation INTRODUCTION The development of functional nanoparticles is of major interest because it was found that the unique properties of such nanoscale materials allow breakthroughs in technology, bioengineering, life sciences, and many others. To tune the properties of the nanoparticles for specific appli- cations, not only the molecular structure but also the size of the systems needs to be well investigated. Therefore, imaging techniques such as atomic force microscopy and scanning and transmission electron microscopy (SEM and TEM) were used to investigate the nanoscale dimensions and morpholo- gies up to the molecular level. In addition, dynamic light scattering (DLS) was applied because it provides more statis- tical information about the average size and size distribution of the particles in suspension. A further and less commonly used method is analytical ultracentrifugation (AUC), which allows a closer look on the flow characteristics of the nano- particles. In the early 20th century, Svedberg already used AUC for the determination of the size and the size distribu- tion of colloids. 1 None of the techniques mentioned provides ultimate information about the size, shape, morphology, and flow behavior of nanoparticular systems. However, a combi- nation of these techniques can lead to a satisfying characteri- zation that is necessary for further improvements and pre- vention of undesired side effects, like aggregation (e.g., of drug-containing particles in the blood stream). Synthetic polymers are widely used materials for the design of functional nanoparticles because they provide unique structural diversity and functionality. In this study, poly (methacrylate) nanoparticles were prepared and analyzed by SEM, DLS, and AUC. Poly(methacrylic acid)-co-(methyl meth- acrylate)s [poly(MAA-co-MMA)] show a pH-dependent solu- bility behavior, which makes it possible to use them as drug delivery systems both able to protect the drug and to release it at the targeted side. 2 In addition, the functionalization of the polymers with dyes allows the localization of the par- ticles for cell studies or tissue examinations. 3,4 To prepare well-defined poly(methacrylate) nanoparticle sus- pensions, nanoprecipitation was applied as alternative tech- nique besides emulsion techniques and spray drying proc- esses usually used for polymers. 5 The nanoprecipitation technique is based on precipitation of polymer molecules Correspondence to: U. S. Schubert (E-mail: ulrich.schubert@uni-jena.de) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 48, 3924–3931 (2010) V C 2010 Wiley Periodicals, Inc. 3924 WILEYONLINELIBRARY.COM/JOURNAL/JPOLA