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

[Display omitted] •Glutamic-acid-based hydro- and nanogels by solution and inverse miniemulsion polymerization.•pH-Sensitive physically and chemically cross-linked hydrogels.•Physically cross-linked hydrogels absorbed up to 160 times their mass in water.•Nanogels are not cytotoxic towards HeLa or L929 cell lines.•Efficient loading of nanogels with a hydrophilic drug. 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.