Biodegradable amphiphilic copolymers were successfully synthesized by the conjugation of various densities of hydrophobic biocompatible cholesterol (Chol) moieties onto poly(2-hydroxyethyl aspartamide) and poly(N-isopropylaminoethyl-co-2-hydroxyethyl aspartamide). These were obtained from polysuccinimde, the thermal polycondensation product of L-aspartic acid, via a ring-opening reaction with multifunctional pendant groups, including ethanolamine and N-isopropylethylenediamine (NIPEDA). Copolymers containing 5-30 mol % Chol showed self-aggregation behavior in aqueous solution, as evidenced by the dynamic light scattering measurement of their particle size distribution. The average particle size of these copolymers increased linearly with increasing Chol content. Moreover, the presence of secondary amine groups in the poly(2-hydroxyethyl aspartamide) NIPEDA system made the conjugation more efficient; however, these also seemed to accelerate the degradation of the copolymers in an aqueous medium. The degradation behavior and pH dependence of the particle size of these copolymers in aqueous solution were also examined. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120: 1685-1693, 2011