Abstract: AIMTo optimize the preparation of sustained release prednisolone-poly(hydroxybutyrate-co-hydroxyvalerate) (PNS-PHBV) nanospheres (NP) using the novel biodegradable materials PHBV as the carriers and PNS as a model drug. METHODSPNS-PHBV nanospheres were prepared by ultrasonic-emulsion technique. The diameter, its distribution and Zeta potential on the surface of particles were measured by means of Zetasizer. RESULTSThe diameter of NP is in the range of 50～250 nm. The drug loading of NP increases but incorporation efficiency and Zeta potential dramatically decrease with increasing ratio of the feeding quantities of drug to those of carriers. The drug release behavior in vitro appeared to have biphasic characteristics with initial burst effect. The more burst effect, the less the diameters of nanoparticles. The longest release time was up to 32 h. CONCLUSIONThe technology of preparation is reasonable and PNS-PHBV nanoparticle showed significant sustained release.