Ipriflavone-Loaded Mesoporous Nanospheres with Potential Applications for Periodontal Treatment

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.

Effects of mesoporous SiO2-CaO nanospheres on the murine peritoneal macrophages/Candidaalbicans interface

“…On the other hand, the present study will allow us to obtain information for the possible future biomedical employment of these mesoporous SiO2-CaO nanospheres in an infection scenario. We have recently shown the utility of this nanomaterial for intracellular drug delivery [34,35]. These previous works have opened the way for future potential profits of this nanomaterial for antifungal delivery by the analysis of the uptake by macrophages of both nanospheres and C. albicans.…”

Effective Actions of Ion Release from Mesoporous Bioactive Glass and Macrophage Mediators on the Differentiation of Osteoprogenitor and Endothelial Progenitor Cells

“…Regarding the mineralization analysis, a slight increase of this parameter was also induced by the presence of MBG-75S deposited on the transwell inserts, but this effect was not statistically significant (right panel Figure 4 ). This slight effect on mineralization was probably due to the need of longer differentiation times, as well as the lower precision and sensitivity of this assay, in comparison with ALP measurement, as we have previously observed in other studies with mesoporous nanospheres and MC3T3-E1 pre-osteoblasts [ 53 ]. Several authors have demonstrated the pro-osteogenic effects of MBGs caused by to the release of calcium and silicon ions [ 54 ], and recent research has shown the influence of these kind of biomaterials on pulp cells behavior in vitro, increasing both ALP activity and mineralization in this cell type [ 55 ].…”

Bioactive Glasses in Periodontal Regeneration: Existing Strategies and Future Prospects—A Literature Review

“…Casarrubios et al [ 54 ] studied mesoporous nanospheres with potential applications for periodontal treatment. The authors evaluated the cytocompatibility of such nanospheres containing ipriflavone (IP), a synthetic isoflavone that prevents osteoporosis.…”

“…With regard to the secondary outcomes, different authors found that, when human cells were used, BGs induced and/or increased cell viability and proliferation, and stimulated mineralized tissue formation [ 37 , 53 , 55 , 66 , 67 , 72 , 75 ], especially when BG nanoparticles were employed [ 55 , 66 ]. When fibroblast/osteocyte cell lines were utilized, cell viability, cell proliferation, cell differentiation were appreciated [ 60 , 64 , 70 , 71 ], in particular with mesoporous BG nanospheres/nanoparticles [ 54 , 68 ]. Some studies detected specific cell factors involved in the osteoinduction response [ 37 , 56 , 59 ], while BGs in membranes promoted healing [ 64 , 65 , 66 , 68 , 69 ].…”