RNA was encapsulated in bovine serum albumin (BSA) microspheres using a one-step sonochemical process from an water-oil solvent biphasic system. Confocal microcoscopy and fluorescence-activated cell sorting indicate that a CY3-RNA (RNA labeled with red fluorescent indocarbocyanine Cy3 dye) sphere is encapsulated in the BSA outer sphere. The diameter of the sphere depends on the number of nucleotides of the RNA, ranging from 0.63 to 2.74 mu m. Total RNA (t-RNA) was used as a prototype for the future small interfering RNA (siRNA) delivery. A very broad size distribution characterizes the RNA spheres and therefore, among the loaded BSA spheres, there were sufficiently small spheres to be successfully introduced into trypanosoma brucei parasites and human osteosarcoma U2OS cancer cells.