  Mesoporous nanospheres in the system SiO2-CaO (NanoMBGs) with a hollow core
surrounded by a radial arrangement of mesopores were characterized, labeled
with FITC (FITC-NanoMBGs) and loaded with ipriflavone (NanoMBG-IPs) in order to
evaluate their incorporation and their effects on both osteoblasts and
osteoclasts simultaneously and maintaining the communication with each other in
coculture. The influence of these nanospheres on macrophage polarization
towards pro-inflammatory M1 or reparative M2 phenotypes was also evaluated in
basal and stimulated conditions through the expression of CD80 (as M1 marker)
and CD206 (as M2 marker) by flow cytometry and confocal microscopy. NanoMBGs
did not induce the macrophage polarization towards the M1 pro-inflammatory
phenotype, favoring the M2 reparative phenotype and increasing the macrophage
response capability against stimuli as LPS and IL-4. NanoMBG-IPs induced a
significant decrease of osteoclast proliferation and resorption activity after
7 days in coculture with osteoblasts, without affecting osteoblast
proliferation and viability. Drug release test demonstrated that only a
fraction of the payload is released by diffusion, whereas the rest of the drug
remains within the hollow core after 7 days, thus ensuring the local long-term
pharmacological treatment beyond the initial fast IP release. All these data
ensure an appropriate immune response to these nanospheres and the potential
application of NanoMBG-IPs as local drug delivery system in osteoporotic
patients.
