Radiation synthesis of poly(acrylic acid) nanogels for drug delivery applications – post-synthesis product colloidal stability

Synthesis of polymer nanogels (NGs) for biomedical applications is considered to be a very promising application in radiation engineering. Under high-dose pulse irradiation of dilute aqueous polymer solution, reactive species generated by water radiolysis can create multiple radicals on each macromolecule and consequently induce intramolecular cross-linking of polymer chains, resulting in NG formation. The obtained products are free from harmful monomers, initiators, and cross-linking agents, which makes them potentially applicable for drug delivery applications. One of the biggest challenges in handling and use of nanoparticles, however, is the colloidal stability, when aqueous suspensions are stored for prolonged periods. Therefore, development of the best protocols for the particular nanocarrier storage is key. To address this need, we have performed the prospective study in which we systematically assessed the influence of various processing and storage scenarios feasible in our lab, on the colloidal stability of the radiation-synthesized poly(acrylic acid) (PAA) NG particles in suspension. This allowed us to choose the optimal way of handling the product after its synthesis. We confirmed that none of the strategies we used and tested are substantially detrimental to our product. Filtration with 0.2-μm filters was proven sufficient for sample purification and prolonged storage in aqueous suspension did not exert a negative effect on the colloidal stability of particles suspension. We have also demonstrated that lyoprotectant-free lyophilization was suitable for our polymer nanoparticles. This is an important fact for further application of particles as nanocarriers for biologically active compounds such as targeting ligands or therapeutic moieties.