The majority of cell encapsulation systems applied so far are based on polyelectrolyte complexes of alginate and polyvalent metal cations. Although widely used, these systems suffer from the risk of disintegration. This can be partially solved by applying chitosan as additional outer membrane. However, chitosan can be dissolved in water only at a low pH, which limits its use in the field of bioencapsulation. In this study, novel primary and tertiary amine chitosan derivatives have been synthesized, which may be dissolved at pH 7.0, and retain the ability to effectively form additional membrane on the surface of alginate beads. As aqueous solutions tertiary amines dimethylamino-1-propyl-chitosan and dimethylethylamine-chitosan with linear hydrochloride aliphatic chains had the lowest toxicity, whereas dimethylpropylamine-chitosan, diethylaminoethyl-chitosan, and diisopropylaminoethyl-chitosan with branched hydrochloride aliphatic were cytotoxic to the majority of tested cells. When applied as polyelectrolyte complexation agent on the surface of alginate beads, none of the derivates had any negative effect on the metabolic activity of encapsulated beta-cells. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.