Pegylated and Thermosensitive Polyion Complex Micelles by Self-Assembly of Two Oppositely and Permanently Charged Diblock Copolymers

Thermosensitive and pegylated polyion complex (PIC) micelles were formed by coassembly of oppositely and permanently charged poly(sodium 2-acrylamido-2-methylpropanesulfonate)-block-poly-(N-isopropylacrylamide), PAMPS-b-PNIPAAM, and poly[(3-acrylmidopropyl)-trimethylammonium chloride]-block-poly(ethylene oxide), PAMPTMA-b-PEO, block copolymers under stoichiometric charge neutralization conditions and polyelectrolyte chain length matching. PAMPTMA-b-PEO block copolymers with different block lengths were prepared for the first time by atom transfer radical polymerization (ATRP) using a PEO macroinitiator. PIC micelles were characterized by H-1 NMR, static light scattering (SLS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). At room temperature, spherical almost monodisperse PIC micelles, consisting of a mixed PAMPTMA/PAMPS coacervate core and a mixed PEO/PNIPAAM shelf, were formed, with size of about 80-110 nm. The PIC micelles completely dissociated to unimers by increasing NaCl concentration above 0.4-0.6 M. PNIPAAM segments in the shell gave rise to a temperature induced transition at 34-37 degrees C forming a hydrophobic shell around the coacervate core in a core-shell-corona type PIC micelle, with it PEO corona which stabilized the nanoparticles in aqueous solution. A fully interconnected and continuous collapsed PNIPAAM shell was formed, with PEO chains forming channels across the PNIPAAM membrane. The association properties of the PIC micelles were influenced by the length of the block segments. Longer polyelectrolyte chains gave rise to bigger micelles, more stable with respect to the ionic strength. PNIPAAM chain length allowed to modulate the temperature of the thermal transition. Long PEO chains (114 repeating units) were necessary to effectively stabilize PIC micelles both below and above LCST of PNIPAAM. Micelle parameters (core radius, R-c, shell radius, R-s, thickness and volume, Delta R-PNIPAAM and V-PNIPAAM, of the collapsed PNIPAAM shell and surface density, Phi of shelf and corona chains before and after the thermal transition) were determined and discussed in terms of block copolymer structure. Precipitation was observed by addition of salt at temperature above LCST because of the release of PEO-b-PAMPTMA chains. A model was proposed explaining the formation and the response to temperature and ionic strength of the PIC micelles. This is the first example of pegylated and thermosensitive PIC micelles having a coacervate core formed by two strong polyelectrolyte blocks with no pH dependence.