Cataldo Russomando Alessandra, Steinberg Doron, Gati Irith, Vogt Sionov Ronit, Eliashar Ron, Friedman Michael, Gross Menachem
Department of Otolaryngology-Head and Neck Surgery, Hadassah Medical Center, Jerusalem 9112102, Israel.
The Biofilm Research Laboratory, The Institute of Biomedical and Oral Research (IBOR), The Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Pharmaceutics. 2023 Mar 22;15(3):1015. doi: 10.3390/pharmaceutics15031015.
The aim of the study was to develop a sustained-release varnish (SRV) containing mometasone furoate (MMF) for sinonasal stents (SNS) to reduce mucosa inflammation in the sinonasal cavity. The SNS' segments coated with SRV-MMF or an SRV-placebo were incubated daily in a fresh DMEM at 37 °C for 20 days. The immunosuppressive activity of the collected DMEM supernatants was tested on the ability of mouse RAW 264.7 macrophages to secrete the cytokines' tumor necrosis factor α (TNFα) and interleukin (IL)-10 and IL-6 in response to lipopolysaccharide (LPS). The cytokine levels were determined by respective Enzyme-Linked Immunosorbent Assays (ELISAs). We found that the daily amount of MMF released from the coated SNS was sufficient to significantly inhibit LPS-induced IL-6 and IL-10 secretion from the macrophages up to days 14 and 17, respectively. SRV-MMF had, however, only a mild inhibitory effect on LPS-induced TNFα secretion as compared to the SRV-placebo-coated SNS. In conclusion, the coating of SNS with SRV-MMF provides a sustained delivery of MMF for at least 2 weeks, maintaining a level sufficient for inhibiting pro-inflammatory cytokine release. This technological platform is, therefore, expected to provide anti-inflammatory benefits during the postoperative healing period and may play a significant role in the future treatment of chronic rhinosinusitis.
本研究的目的是开发一种含糠酸莫米松(MMF)的缓释清漆(SRV),用于鼻鼻窦支架(SNS),以减轻鼻腔黏膜炎症。将涂有SRV-MMF或SRV安慰剂的SNS段每天在新鲜的DMEM中于37°C孵育20天。对收集的DMEM上清液的免疫抑制活性进行测试,观察其对小鼠RAW 264.7巨噬细胞响应脂多糖(LPS)分泌细胞因子肿瘤坏死因子α(TNFα)、白细胞介素(IL)-10和IL-6能力的影响。通过各自的酶联免疫吸附测定(ELISA)测定细胞因子水平。我们发现,从包被的SNS释放的MMF每日量足以分别在第14天和第17天之前显著抑制巨噬细胞中LPS诱导的IL-6和IL-10分泌。然而,与涂有SRV安慰剂的SNS相比,SRV-MMF对LPS诱导的TNFα分泌只有轻微的抑制作用。总之,用SRV-MMF包被SNS可实现MMF至少2周的持续释放,维持足以抑制促炎细胞因子释放的水平。因此,该技术平台有望在术后愈合期提供抗炎益处,并可能在未来慢性鼻-鼻窦炎的治疗中发挥重要作用。