Biodegradable capsules of size around 350 nm were prepared by layer-by-layer (L-b-L) assembly of oppositely charged chitosan and dextran sulfate on silica particles and the subsequent removal of template. The resulting capsules were loaded with rifampicin, an anti-tuberculosis drug under modest conditions, as demonstrated by scanning electron microscopy (SEM). Maximum encapsulation of rifampicin was found to be about 82 μg at 25 ℃ and pH of 3. Release studies were done in-vitro mode by semiautomatic release protocol, with different pH solutions in water and phosphate buffered saline (PBS). The microcapsules exhibited a slow and sustained release over 72 hours and maximum release was obtained at a pH of 1.2 in water and a pH of 7.4 in PBS. The size of silica particle was analyzed by dynamic light scattering method. Scanning electron microscopy (SEM) measurements showed the surface morphology of the hollow capsules. UV spectroscopy was employed to monitor the drug release processes in both solutions. The kinetics of drug release mechanism was studied using Ritger-Peppas and Higuchi models.