Alginate microparticles and nanoparticles crosslinked with Ca+2 ions are frequently employed in biomedical applications. Here we use microemulsion polymerization to prepare alginate nanoparticles (nano gels) using different crosslinking ions (Ca+2, Sr+2, Ba+2) to encapsulate a model protein, urease enzyme (jackbeans). With alginate concentrations of 0.2 wt% in the aqueous phase, emulsion droplets showed good stability and narrow, monomodal distributions with radii similar to 65 +/- 10 nm. The size of the nanogel varies with the crosslinking cation and its affinity for the mannuronate and guluronate units in the linear alginate chain. The nanogels were further characterized using dynamic light scattering, scanning electron microscopy, energy dispersive X-ray spectrometry and zeta potential. This work demonstrates the potential application of Ba-alginate as an alternative matrix for nano-encapsulation of proteins and its use for biomedical applications. (C) 2016 Elsevier Inc. All rights reserved.