负载依普黄酮的介孔SiO2-CaO纳米微球对成骨细胞/破骨细胞共培养的影响
Incorporation and effects of mesoporous SiO2-CaO nanospheres loaded with ipriflavone on osteoblast/osteoclast cocultures
摘要：
在系统SiO2-CaO（NanoMBGs）中的介孔纳米球的特征在于，用FITC（FITC-NanoMBGs）标记和负载依普黄酮（NanoMBG-IP），以评估它们的掺入和它们对成骨细胞和破骨细胞的影响，同时保持共培养中彼此之间的通信。这些纳米球对巨噬细胞向促炎性M1或修复性M2表型极化的影响也在基础和刺激条件下通过流式细胞术和共聚焦显微镜通过CD 80（作为M1标志物）和CD 206（作为M2标志物）的表达进行评价。NanoMBG不诱导巨噬细胞向M1促炎表型极化，有利于M2修复表型，并增加巨噬细胞对LPS和IL-4等刺激物的反应能力。与成骨细胞共培养7天后，NanoMBG-IP诱导破骨细胞增殖和吸收活性显著降低，而不影响成骨细胞增殖和活力。药物释放试验表明，只有一小部分有效载荷通过扩散释放，而其余药物在7天后仍保留在中空核内，从而确保局部长期药理学治疗超过初始快速IP释放。所有这些数据确保了对这些纳米球的适当免疫应答以及NanoMBG-IP作为局部药物递送系统在糖尿病患者中的潜在应用。
英文摘要：
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.
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