The design of chitosan microspheres for the encapsulation and release of nanoparticles has been considered. The composite microcarriers have been produced by spray drying and the effect of factors including the chitosan cross-linking ratio (using tri-polyphosphate as the cross-linking agent), nanoparticle loading in the polymer matrix and the internal structure of the microspheres (uniform dispersion of nanoparticles vs. core-shell structure) on the in vitro release kinetics have been systematically investigated. The antibacterial performance of the composite microspheres containing Ag nanoparticles has been evaluated against three different strains of bacteria in a suspension culture. The bioadhesive character of the chitosan carrier particles has lead to the formation of stable aggregates with the bacteria, which enhanced the antibacterial efficacy of the released nanoparticles through the contact mechanism.