A new family of nanoscale materials on the basis of dispersed networks of cross-linked ionic and nonionic hydrophilic polymers is being developed. One example is the nanosized cationic network of cross-linked poly(ethylene oxide) (PEO) and polyethyleneimine (PEI), PEO-cl-PEI nanogel. Interaction of anionic amphiphilic molecules or oligonucleotides with PEO-cl-PEI results in formation of nanocomposite materials in which the hydrophobic regions from polyion-complexes are joined by the hydrophilic PEO chains. Formation of polyion-complexes leads to the collapse of the dispersed gel particles. However, the complexes form stable aqueous dispersions due to the stabilizing effect of the PEO chain. These systems allow for immobilization of negatively charged biologically active compounds such as retinoic acid, indomethacin and oligonucleotides (bound to polycation chains) or hydrophobic molecules (incorporated into nonpolar regions of polyion-surfactant complexes). The nanogel particles carrying biological active compounds have been modified with polypeptide ligands to enhance receptor-mediated delivery. Efficient cellular uptake and intracellular release of oligonucleotides immobilized in PEO-cl-PEI nanogel have been demonstrated. Antisense activity of an oligonucleotide in a cell model was elevated as a result of formulation of oligonucleotide with the nanogel. This delivery system has a potential of enhancing oral and brain bioavailability of oligonucleotides as demonstrated using polarized epithelial and brain microvessel endothelial cell monolayers.

Block ionomer complexes formed between the block copolymers containing poly(sodium methacrylate) (PMANa) and poly(ethylene oxide) (PEO) segments and poly(N-ethyl-4-vinylpyridinium bromide) (PEVP) were investigated. The data obtained suggest that (i) these systems form water-soluble stoichiometric complexes; (ii) these complexes are stable in a much broader pH range compared to the polyelectrolyte complexes prepared from homopolymers; (iii) they self-assemble to form the core of a micelle comprised of neutralized polyions, surrounded by the PEO corona; (iv) they are salt sensitive since they fall apart as the salt concentration increases beyond a critical value; and (v) they can participate in the cooperative polyion substitution reactions. Therefore, these complexes represent a new class of hybrid materials which combine properties of polyelectrolyte complexes and block copolymer micelles.