Drug-loadable Mesoporous Bioactive Glass Nanospheres: Biodistribution, Clearance, BRL Cellular Location and Systemic Risk Assessment via (45)Ca Labelling and Histological Analysis.

Baiyan Sui,Gaoren Zhong,Jiao Sun

doi:10.1038/srep33443

Baiyan Sui, Gaoren Zhong + Show 1 more

Open Access

https://doi.org/10.1038/srep33443

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Journal: Scientific Reports	Publication Date: Sep 15, 2016
Citations: 25	License type: CC BY 4.0

Affiliation: Shanghai Ninth People's Hospital

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.

Highlights

Mesoporous bioactive glass (MBG) nanospheres are mainly composed of silica and calcium[6]
It has been reported that the introduction of functional groups to nanoparticles by APTES could facilitate the coupling of nanoparticles with drugs, fluorescein, and decrease drug burst release of drug carriers[14,15]
The band at 1455.3 cm−1 presented a more intense vibration formed by the protonated amine groups (−NH3+), which may be related to the aqueous phase of amino adsorption or neighboring silanol groups[17], and this phenomenon demonstrated that MBG nanospheres were successfully grafted an -NH2 group

Summary

Introduction

MBG nanospheres are mainly composed of silica and calcium[6]. At present, to detect the distribution of silica matrix nanoparticles in vivo, inductively coupled plasma-optical emission spectroscopy and inductively coupled www.nature.com/scientificreports/. Plasma-mass spectrometry are used to determine the silica content[2,7,8] These methods were used to acquire the quantitative data, but most of them have some problems, for example, the sensitivity of detection was reduced due to diluting samples before testing, and the data was subjected to interference by allochthonous impurities during the processing of samples or inherent elements in the body. MBG nanospheres was synthesized and labeled in situ by introducing radionuclide 45Ca. So as to better understand the regular pattern of MBG nanospheres systemic metabolism, we studied their residence time in blood, distribution and accumulation in various organs, excretion pathway, and further studied hepatocellular intracellular locations and the effects on mitochondrial function. Our study provide critical scientific basis for clinical application of drug-loadable MBG nanospheres

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