Preparation of Calcium-Phosphate Microspheres by Salt-Assisted Ultrasonic Spray-Pyrolysis Technique and their Drug Release Behavior Using Anti-Angiogenic Agent, TNP-470

Abstract

Synthetic clcium phosphate based materials, such as hydroxyapatite (Ca10(PO4)6(OH)2; HAp) and tricalcium phosphate (Ca3(PO4)2; TCP), are compounds with high potential for clinical applications to orthopedic and dental region. In previous study, we have reported that the hollow and porous apatite microsphere could be prepared by salt-assisted ultrasonic spray-pyrolysis (SAUSP) technique using sodium chloride (NaCl). In this case, these microspheres have some problems of (i) decrease of dissolubility of microspheres and (ii) cytotoxicity arising from chloride ions elution. To overcome these disadvantages, we prepared novel microspheres by SAUSP technique using potassium nitrate (KNO3) instead of NaCl. The resulting microsphere was washed with pure water to remove the KNO3 phase. The particle shapes of the powders were observed by scanning electron microscopy (SEM); the diameters of the microspheres were of 0.5 - 3.0 m, and the fine pores with the sizes of ~50 nm were present on the surface of the microspheres. The TNP-470 agent as a model of drug were loaded on these microspheres with nano-pores in the surface. In the KNO3 concentration of 1.00 mol·dm-3, 70 % of the total TNP-470 from the microspheres was rapidly released within 1 h. The remaining 30 % was slowly released up to 24 h following immersion, and total amount of TNP-470 released from the microspheres was 42 g·mg-1.