Controllable fabrication of hollow TiO2 spheres as sustained release drug carrier

Abstract TiO 2 hollow spheres with controllable size were successfully synthesized through a hydrothermal silica etching method; SiO 2 cores were easily removed without the use of a toxic reagent. The parameters for the synthesis of SiO 2 cores and TiO 2 hollow spheres, including stirring time, ammonia concentration, tetrabutyl titanate content, hydrothermal time, and reflux time, were systematically investigated. SiO 2 cores and TiO 2 hollow structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectra (EDX), X-ray photoelectron spectroscopy (XPS), and N 2 adsorption-desorption isotherms. The results revealed that the mean diameter of SiO 2 was ∼280 nm when the concentration of ammonia was 4.8 M and the stirring time was 0.5 h. For hollow TiO 2 , when the operation process was optimized (ammonia volume 0.35 mL, TBOT addition 1.5 mL, hydrothermal time 3 h, and reflux time 3 h), the average size and the shell thickness were 270 and 100 nm, respectively. The process exhibited a high drug loading capacity (33.12 ± 0.01%) and encapsulation rate (99.03 ± 0.24%) due to its high specific surface area of 121.62 m 2 ·g −1 . In addition, TiO 2 hollow spheres displayed pH-responsive sustained-controlled drug release behavior in vitro which released 80% of doxorubicin at 5.0 pH within 120 h, its release kinetic showed that it fits well with Zero-order kinetic equation, demonstrating that DOX·HCl/hollow TiO 2 maintains constant release rate, and the investigation of blood compatibility showed that the hemolysis rate of hollow TiO 2 did not exceed 3% in the concentration range of 100 and 4000 μg/mL, further confirming that prepared hollow TiO 2 is a relatively safe medical inorganic material.