Systemic distribution and biological safety of mesoporous bioactive glass nanoparticles by 45Ca labeling, tracing, and histological evaluation

摘要

Introduction: Mesoporous bioactive glass (MBG) nanoparticles had the advantage of high loading efficiency!1', but it is still unknown its state in vivo on early stage, which is directly bearing on pharmacodynamics and the organism's biological risks. Therefore, it is necessary to explicit the distribution and potential risks to organism. In this study, the synthesis of MBG nanoparticle was introduced by radionuclide calcium (45Ca), the distribution of MBG nanoparticle in major tissues and organs was analyzed within 72 hours. Finally, whether MBG nanoparticle caused a histopathologic reaction was evaluated. Experimental Section: A hydrothermal method using 45Ca (NO3)2·4H2O, TEOS and TEP in combination with CTAB and PVP co-templates was applied to prepare 45Ca-MBG nanoparticles. MBG nanoparticles were characterized by transmission electron microscopy (TEM). The size and zeta potential in physiological saline were performed on a ZetaSizer. Then twenty ICR mice were intravenously injection by 45Ca-MBG nanoparticles. Then the blood, heart, lung, liver, spleen, and kidney were harvested, and the tissue distribution was expressed as the percentage injected dose per gram tissue (%ID/g). Finally ICR mice were injected via tail vein with nanoparticles (physiological saline set as control). After 72h, the major organs were collected, and the histopathological change was evaluated. Results and Discussion: The establishment of an effective labeling technique is considered to come first on monitoring the distribution of MBG nanoparticles in vivo. In this study, the size of obtained 4SCa-MBG nanoparticles with a mesostructure was in the range of 50-100 nm. The hydrodynamic size, increased by slightly agglomeration, was 177.7nm. The nanoparticles remained the low negative surface charge (-11.7mV) which may be suitable as a drug vehicle in clinical. Furthermore, the nanoparticles were mainly distributed in the blood and major organs. The radioactivity peaked at 12 hours and then declined gradually. The accumulation of MBG nanoparticles in liver was higher than that of other organs. This phenomenon could be interpreted that the size of MBG nanoparticles, which was smaller than the reticuloendothelial gap of liver, was in favor of intrahepatic transport. Ultimately, there was no obvious pathological change in the major organs. Conclusion: This study has created an effective quantitative tracer for the 4SCa labeling of MBG nanoparticles. The results demonstrated that post injection in mice, 45Ca-MBG nanoparticles distributed in the heart, lungs, liver, spleen and kidneys through blood circulation, and did not cause histopathological changes. These findings preliminarily addressed the benefits and risks of MBG nanoparticles as nano drug delivery. Figure 1. TEM image for MBG nanoparticles Figure 2. Quantitative tissue distribution of 45Ca-MBG nanoparticle in major tissues.