Nanosized drug delivery systems are promising tools in the field of nanomedicine applied to cancer. A novel temozolidomidehydroxyapatite (TMZ/HAp) sustained-release nanopreparation for implantation in glioblastoma multiforme (GBM) patients was designed, synthesized and characterized in this study. The structure, morphology, drug loading and in vitro delivery properties of the HAp particles and the novel polysuccinimide (PSI)-coated HAp(HAp-PSI) nanoparticles were evaluated using X-ray powder diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-performance liquid chromatography. The TMZ/HAp-PSI nanoparticles consist of a flower-like HAp core enclosed by a smooth PSI layer, which presents a spherical or nearly spherical form. The TMZ/HAp-PSI nano particles further strengthen the encapsulation efficiency to 93M%. Compared with TMZ/HAp alone, both the TMZ/HAp-PSI nanoparticles and TMZ/HAp-PSI tablets can prolong the drug release time to more than 350 h and avoid an early burst drug release, suggesting a great potential for the brain or bone implantation drug delivery applications.