title: Drug-loadable Mesoporous Bioactive Glass Nanospheres: Biodistribution, Clearance, BRL Cellular Location and Systemic Risk Assessment via (45)Ca Labelling and Histological Analysis.
abstract: Mesoporous bioactive glass (MBG) nanospheres with excellent drug loading property have attracted significant attention in the field of nano-medicine. However, systemic metabolism and biosafety of MBG nanospheres which are crucial issues for clinical application are yet to be fully understood. Isotope quantitative tracing combined with biochemical parameters and histopatological changes were used to analyze biodistribution, excretion path and the effect on metabolism and major organs, and then we focused on the hepatocellular location and damaging effect of MBG. The results indicated MBG possessed a longer residence time in blood. After being cleared from circulation, nanospheres were mainly distributed in the liver and were slightly internalized in the form of exogenous phagosome by hepatocyte, whereby more than 96% of nanospheres were located in the cytoplasm (nearly no nuclear involvement). A little MBG was transferred into the mitochondria, but did not cause ROS reaction. Furthermore, no abnormal metabolism and histopathological changes was observed. The accumulation of MBG nanospheres in various organs were excreted mainly through feces. This study revealed comprehensively the systemic metabolism of drug-loadable MBG nanospheres and showed nanospheres have no obvious biological risk, which provides a scientific basis for developing MBG nanospheres as a new drug delivery in clinical application.
authors.affiliation: Shanghai Biomaterials Research &Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.
authors.forename: Baiyan
authors.initials: B
authors.lastname: Sui
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Gaoren
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Shanghai Biomaterials Research &Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D002132:Calcium Radioisotopes / Q000737:chemistry*; D016923:Cell Death; D002470:Cell Survival; D016503:Drug Delivery Systems; D005243:Feces / Q000737:chemistry; D005898:Glass / Q000737:chemistry*; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008813:Mice, Inbred ICR; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D018384:Oxidative Stress; D016062:Porosity; D018570:Risk Assessment; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D002132:Calcium Radioisotopes; C000615351:Calcium-45