Ipriflavone-Loaded Mesoporous Nanospheres with Potential Applications for Periodontal Treatment.

Laura Casarrubios,Daniel Arcos,María Vallet-Regí,María Teresa Portolés,María José Feito,Natividad Gómez-Cerezo

doi:10.3390/nano10122573

Abstract

The incorporation and effects of hollow mesoporous nanospheres in the system SiO2–CaO (nanoMBGs) containing ipriflavone (IP), a synthetic isoflavone that prevents osteoporosis, were evaluated. Due to their superior porosity and capability to host drugs, these nanoparticles are designed as a potential alternative to conventional bioactive glasses for the treatment of periodontal defects. To identify the endocytic mechanisms by which these nanospheres are incorporated within the MC3T3-E1 cells, five inhibitors (cytochalasin B, cytochalasin D, chlorpromazine, genistein and wortmannin) were used before the addition of these nanoparticles labeled with fluorescein isothiocyanate (FITC–nanoMBGs). The results indicate that nanoMBGs enter the pre-osteoblasts mainly through clathrin-dependent mechanisms and in a lower proportion by macropinocytosis. The present study evidences the active incorporation of nanoMBG–IPs by MC3T3-E1 osteoprogenitor cells that stimulate their differentiation into mature osteoblast phenotype with increased alkaline phosphatase activity. The final aim of this study is to demonstrate the biocompatibility and osteogenic behavior of IP-loaded bioactive nanoparticles to be used for periodontal augmentation purposes and to shed light on internalization mechanisms that determine the incorporation of these nanoparticles into the cells.

Highlights

Bioactive glasses are a group of bioceramics that exhibit bone regeneration properties
We have evaluated the effects of mesoporous bioactive nanospheres loaded with IP on MC3T3-E1 osteoprogenitor cells, the most relevant model of in vitro osteogenesis [28], as a nanotherapeutic strategy to promote bone regeneration
Since the effectiveness of treatment with nanoparticles designed for intracellular drug release depends on their efficient incorporation into cells, we have investigated the mechanisms of incorporation of these nanospheres into pre-osteoblasts

Summary

Introduction

Bioactive glasses are a group of bioceramics that exhibit bone regeneration properties. Since their discovery in 1971, over 1.5 million patients have been treated with Bioglass 45S5, the original four-component Bioglass composition (45 wt % SiO2, 24.5 wt % CaO, 24.5 wt % Na2O, 6 wt % P2O5). In addition to orthopedic surgery as bone graft substitutes, bioactive glasses applications in dentistry involve their use as dental restorative materials, mineralizing agents, coating material for dental implants, pulp capping and root canal treatment [1]. The research developed during the subsequent decades has resulted in new materials that significantly differs from the original melt-derived Bioglass 45S5. The use of the sol–gel process in the

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