Refined Polyelectrolyte Complex Nanoparticles


Polymer nanoparticles are progressively used beside classical applications like coatings and paints for the immobilization, storage and transport of drugs or proteins. In that context the nano dimension offers a high surface/volume ratio and the correlation with structural sizes typical in biological systems. The aims of our work are to prepare polyelectrolyte complex based nanoparticles and to explore their potential as protein and drug carriers. Specific issues are dedicated to the improvement of preparation reproducibility and of size uniformity, the formation process should be better understood and possibilities should be explored to bind proteins and drugs under conservation of colloidal stability.

Materials and Methods

Typical PEC dispersions are prepared in our lab by mixing solutions of e.g. PDADMAC and poly(L-lysine) with those of  copolymers of maleic acid (PMA-X) or poly(styrenesulfonate) (PSS) followed by consecutive centrifugation and separation [1]. Important parameters are the the molar mixing ratio (n-/n+), concentration, pH value and ionic strength. Applied methods are dynamic light scattering (DLS), colloid titration (PCD) and circular dichroism (CD) at the dispersions as well as scanning force microscopy (SFM) and fourier transform infrared (FTIR) spectroscopy at the particle layers.


Fig. 1: Aggregation of primary and narrowed size distribution of secondary particles by centrifugation (0x, 1x, 2x) [1].

PEC raw dispersions initially show polymodal size distributions of nanoparticles. However, by consecutive centrifugation and separation of the coacervate phase monomodal distributions can be achieved, which we explain as an “accelerated ripening” of the raw dispersion (Ostwald). By centrifugation primary particles (radius < 20 nm) aggregate via short range dispersive interactions to secondary particles (> 75 nm, Coacervatphase) as well as larger precipitate structures (Fig. 1) and the unreacted polyelectrolyte (PEL) is separated.
Colloid stability of the secondary particles is provided by long range electrostatic repulsion between the particle shells, which consist of the excess PEL. Via n-/n+ <> 1 anionic and cationic particles can be prepared and via the concentration and ionic strength defined sizes can be provided.
In that context the influence of the Debye length on PEC particle size has been addressed by simulation studies. A simulation concept of Prof. Lebovka (Institute of Biocolloidal Chemistry, Kiew) based on the diffusion theory of Smoluchowskii and the stability/coagulation theory of Fuchs considering the colloid potential of DLVO theory was applied. In the Fig. 2 the simulation concept and the comparison of the experimental and simulated particle radii are shown.
Furthermore, beside classical spherical PEC particles also needle like PEC particles can be prepared, if molecularly stiff PEL are used. (Fig. 3) [2].
Finally, model proteins can be bound at PEC nanoparticles under electrostatically repulsive conditions, where the formed PEC/protein conjugate particles show a comparable stabilliy and size uniformity (Fig.4) [3].

Fig. 2: Simulation concept and comparison of experimental and simulated data on the Debye length dependence of the PEC particle radius (r m)
Fig. 3: Spherical (right: PLL/PMA-MS) and needle like (left: PLL/PMA-P) PEC nano particles [2].
Fig. 4: PEC/protein conjugate of PDADMAC/PSS and human serum albumin (SFM image and scheme from [3])

We like to thank German Research Foundation (DFG) (MU 1524/2-1 und SFB 287, B5) for financial support.


[1]  M. Müller, B. Keßler, S. Richter, Langmuir, 21(15), 7044-7051 (2005)
[2]  M. Müller, T. Reihs, W. Ouyang, Langmuir, 21(1), 465-469 (2005)
[3]  W. Ouyang and M. Müller, Macromol. Bioscience, 6, 929-941 (2006)