Spray-dried chitosan microparticles with controlled size were prepared and crosslinked with the biocompatible reactant d,l -glyceraldehyde. Glutaraldehyde, the conventional cross-linking agent for proteins, was used as a control. The crosslinking degree was characterized through thermal analysis, X-ray diffraction, and infrared spectroscopy. In addition, the crosslinking effects were analyzed in terms of particle size, swelling capability, and surface charge. By properly choosing d,l -glyceraldehyde concentration and crosslink time, a high degree of control was achieved over the physical properties of particles. Yields around 78% as well as images obtained through fluorescence microscopy demonstrated the capability of the crosslinked chitosan microspheres to pDNA complexation.243373382