Hollow microcapsules, composed of pH responsive polyelectrolytes via a layer-by-layer (LBL) adsorption technique, were prepared. Linear or star-shaped poly(glycerol metha crylate)s (PGOHMAs) modified with 1,4-butanediamine and 1,2-ethanediamine (EDA) were synthesized and used as polycations. Poly(acrylic acid) was employed as polyanion and SiO2 (about 170 nm) as template. After LBL absorption, SiO2 cores were removed by HF treatment. The particle size and zeta potential were measured by dynamic light scattering, showing that the diameter of star-shaped amino-PGOHMA was larger than linear counterpart. The LBL assembly and core-etching process were evidenced by scanning electron microscope, transmission electron microscope, and energy dispersive spectrometer. The cytotoxicity experiments on human umbilical vein endothelial cells were carried out to evaluate the toxicity of LBL assembly. The star-shaped and EDA-modified PGOHMA exhibited better cell viability. The microcapsules were then used to load an anticancer drug, doxorubicin hydrochloride. High loading capacity (about 42%) and entrapment efficiency (84%) were obtained for star-shaped polymer-based microcapsules. The cumulative release rate was evaluated in vitro, showing faster release at an acidic condition compared to neutral pH. Confocal laser scanning microscopy evidenced the successful cellular uptake of DOX-loaded microparticles. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.