pH-responsive physically and chemically cross-linked glutamic-acid-based hydrogels and nanogels

Given the great demand for polymers prepared from renewable materials, the synthesis of a glutamic-acid-based hydrogel by solution and inverse miniemulsion polymerization is herein presented. Free radical initiated homopolymerizations of N-acryloyl-L-glutamic acid (L-AGA) resulted in either a readily water-soluble polymer or a physically cross-linked hydrogel, being the formation of physical cross-linking junctions closely related to monomer concentration and mixture viscosity. Chemically cross-linked poly(L-AGA-co-BIS) hydrogels were also synthesized by copolymerization of L-AGA and N,N'-methylenebis(acrylamide) (BIS). Both poly(L-AGA) and poly (L-AGA-co-BIS) swelling behavior were found to be pH-dependent and induced by protonation/deprotonation of the polymer three-dimensional network. Poly(L-AGA) and poly(L-AGA-co-BIS) nanogels with average sizes ranging from 280 to 370 nm (in swollen state) were further synthesized by a straightforward inverse miniemulsion polymerization and were efficiently loaded with doxorubicin. Cytotoxicity of nanogels against HeLa or L929 cells demonstrated that both poly(L-AGA) and poly(L-AGA-co-BIS) are non-toxic. The obtained results show that L-glutamic-acid-based nanogels may have a great potential in hydrophilic drug nanocarriers.