Poly(methyl vinyl ether-alt-maleic anhydride) (PMM0) (vas partially hydrolyzed in a 9/1 acetonitrile-d(3)/D2O mixture and then diluted with an aqueous buffer and coated onto poly-L-lysine (PLL)-coated calcium alginate capsules. The resulting 50% hydrolyzed polymer (PMM50) is bound to the surface-immobilized PLL through both electrostatic and covalent interactions, resulting in a shell-cross-linked hydrogel capsule that is resistant to chemical challenges. Further hydrolysis of PMM50 in aqueous buffer was monitored by potentiometry and was found to proceed with a half-life time of about 2.5 min at 20 degrees C such that residual anhydride groups not consumed by cross-linking with PLL would be deactivated by hydrolysis within several minutes of shell formation, removing potential sites for undesired protein binding. Initial protein-binding tests involving incubation of the capsules in bovine serum albumin solutions for 24 h showed no indication of protein binding. The effects of coating temperature, PLL concentration and molecular weight, PMM50 molecular weight. and multiple PLL-PMM50 coatings on shell morphology and behavior were studied using confocal fluorescence microscopy as well as chemical challenges involving sodium citrate and sodium hydroxide. The resilience of the cross-linked shell improved with increasing concentrations of PLL and decreasing molecular weight of PMM50. both of which resulted in more polyelectrolyte being bound to the capsule. The permeability of these covalently cross-linked capsules was studied using fluorescently labeled dextrans and was found to be comparable to standard calcium alginate-PLL-alginate (APA) Capsules.