Incorporation and effects of mesoporous SiO2-CaO nanospheres loaded with ipriflavone on osteoblast/osteoclast cocultures

TL;DR

This study develops mesoporous SiO2-CaO nanospheres loaded with ipriflavone, demonstrating their potential to modulate immune responses and inhibit osteoclast activity, supporting their use as targeted drug delivery in osteoporosis treatment.

Contribution

The paper introduces a novel mesoporous nanosphere system loaded with ipriflavone that effectively modulates immune response and osteoclast activity without affecting osteoblasts.

Findings

NanoMBGs favor M2 macrophage phenotype and enhance immune response.

NanoMBG-IPs decrease osteoclast proliferation and resorption activity.

Drug release is sustained within the nanospheres for over 7 days.

Abstract

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.