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pH Sensitive Polymer Nanoparticles: Effect of Hydrophobicity on Self-Assembly r Konak,† Martin Hruby,† Hana Mackova,† Sergey K. Filippov,*,† Larisa Starovoytova,† Cestmı´ ‡ epanek† G€oran Karlsson, and Petr St † Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic, and ‡Department of Physical and Analytical Chemistry, Uppsala University, Box 579, SE-75123, Uppsala, Sweden
Received May 11, 2010. Revised Manuscript Received July 12, 2010 The influence of hydrophobicity on formation, stability, and size of pH-responsive methacryloylated oligopeptidebased polymer nanoparticles has been studied by dynamic light scattering (DLS), transmission electron microscopy (Cryo-TEM), and NMR. Different polyanions/surfactant systems have been studied at constant polymer concentration and within a broad range of surfactant concentrations. The two newly synthesized pH-sensitive hydrophobic polyanions, poly(Nω-methacryloyl glycyl-L-leucine) and poly(Nω-methacryloyl glycyl-L-phenylalanyl-L-leucinyl-glycine), and three nonionic surfactants (Brij97, Brij98, and Brij700) have been investigated. The surfactants were different in the length of hydrophilic poly(ethylene oxide) (PEO) chain. In surfactant-free solution at basic pH, the polyanions form hydrophobic domains. In the presence of a surfactant, our results prove the complex formation at high pH between the nonionic surfactant and the polyelectrolyte; a pearl-necklace structure is formed. At low pH below critical pH (pHtr), reversible nanoscale structures occur in solutions for all systems. The detailed mechanism of the formation of pH-sensitive nanoparticles from polymer-surfactant complex with varying pH is established. Our results suggest that the polymer hydrophobicity is of primary importance in pretransitional behavior of the complex. Once preliminary nanoparticle nuclei are formed, the hydrophobicity of the polymer plays a minor role on further behavior of formed nanostructures. The subsequent transformation of nanoparticles is determined by the surfactant hydrophilicity, the length of hydrophilic tail that prevents further aggregation due to steric repulsions.
Introduction When a polymer in solution is moved to a region of a phase diagram with low solubility, that is, by a change in pH, temperature, or solvent composition, the extent of macrophase separation of the polymer can be controlled by addition of a surfactant. By fine-tuning of the physicochemical details of this procedure, welldefined nanoparticles can be obtained with a controlled size and polydispersity.1 We have demonstrated the applicability of this procedure on model systems with nanoparticles prepared by a change in temperature,2,3 by solvent shifting,4 and by a change in pH.5 In this contribution, we describe new oligopeptide polymers with direct applicability in targeted delivery research the structural, kinetic, and dynamic details of the nanoparticle formation. This is possible thanks to a combination of several experimental methods: NMR, cryogenic transmission electron microscopy (Cryo-TEM), zeta-potential, and light scattering. We have shown previously in a Brij98/polyanion system that, in a certain range of concentrations and composition particles, a broad range of sizes ca. 20-200 nm could be reproducibly prepared after a change of pH from 7 to 2. This change is reversible, and the nanoparticles can be repeatedly created and dissolved by a variation in pH. Under certain circumstances, the nanoparticles *To whom correspondence should be addressed. E-mail:
[email protected]. (1) Holmberg, K.; Jonsson, B.; Kronberg, B, Lindman, B. Surfactants and Polymers in Aqueous Solution; John Wiley & Sons: New York, 2002. (2) Konak, C; Hruby, M. Macromol. Rapid Commun. 2006, 27, 877. (3) Konak, C; Panek, J.; Hruby, M. Colloid Polym. Sci. 2007, 285, 1433. (4) Panek, J.; Filippov, S.; Konak, C.; Nallet, F.; Noirez, L.; Karlsson, G.; Stepanek, P. J. Dispersion Sci. Technol., in press; DOI: 10.1080/01932691.2010.488475. Mackova, H.; Spı´ rkova, M.; St epanek, (5) Filippov, S.; Hruby, M.; Konak, C.; P. Langmuir 2008, 24, 9295–9301.
14450 DOI: 10.1021/la1018778
are very monodisperse. It has been shown that the polydispersity of nanoparticles obeys a parabolic law as a function of composition.5 In this paper, we describe the molecular mechanism of nanoparticle formation. Indeed, despite the fact that polymer-surfactant complexes have been studied for many decades and more or less all agents responsible for complex formation were identified, a detailed picture of the surfactant-polymer interactions at the molecular level is still missing. It is known that surfactant molecules at a concentration defined usually as C1 (C1
