The aim of this study was to formulate and characterize microspheres containing antisense oligonucleotide to NF-kappaB using bovine serum albumin as the polymer matrix. Microspheres were prepared by spray-drying technique with 5, 10 and 15% drug loading. Glutaraldehyde was used as a cross-linking agent. The particle sizes ranged from 3-5 microm. Microspheres were smooth and spherical in shape, as determined by scanning electron microscopy (SEM). The yield of microspheres ranged from 70-75% and the encapsulation efficiencies were found to be in the range of 59-60%, as determined by a novel HPLC method. Zeta potential of the microspheres ranged between -39 to -53 mV, thus indicating good suspension stability in water. In-vitro release studies performed using phosphate buffer saline demonstrated extended drug release up to 72 h. Kinetic model fitting showed high correlation with the Higuchi model, suggesting that the drug release was primarily diffusion controlled.