Department of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China,
Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai 201620, China,
Int J Nanomedicine. 2019 Feb 4;14:963-976. doi: 10.2147/IJN.S182073. eCollection 2019.
Combined therapies utilizing inhibitors to remove pathogens are needed to suppress lipopolysaccharide (LPS)-induced periodontal disease. We prepared a novel, multi-agent delivery scaffold for periodontal treatment.
In this study, we synthesized SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor) drug-loaded poly(ethylene glycol)-block-caprolactone copolymer via dialysis method. The physical property of micelles was characterized through dynamic light scattering and transmission electron microscopy. The cell growth and LPS-induced MMP-2 and MMP-13 expression were evaluated through CCK-8, real-time PCR and Western blot assay. The release of SP600125 and SB203580 from different scaffolds was estimated. Microcomputed tomography and histology were used for evaluating the effect of the micelles-loaded nanofibers on the treatment of class II furcation defects in dogs.
The drug was then successfully incorporated into gelatin fibers during electrospinning process. We confirmed that the micelles had spherical structure and an average particle size of 160 nm for SP600125-micelles (SP-Ms) and 150 nm for SB203580-micelles (SB-Ms). The nanofiber scaffold showed excellent encapsulation capability, in vitro drug-release behavior, and cell compatibility. Real-time PCR and Western blot assay further indicated that LPS-induced MMP-2 and MMP-13 expression was significantly inhibited by the scaffold.
The results suggested that the dual drug-loaded system developed in this study might become a highly effective therapy for periodontal disease.
需要利用抑制剂的联合疗法来清除病原体，以抑制脂多糖（LPS）诱导的牙周病。我们制备了一种新型的多药递送支架用于牙周病治疗。
在这项研究中，我们通过透析法合成了 SP600125（JNK 抑制剂）和 SB203580（p38 抑制剂）载药聚乙二醇-嵌段-己内酯共聚物。通过动态光散射和透射电子显微镜对胶束的物理性质进行了表征。通过 CCK-8 法、实时 PCR 和 Western blot 检测评估细胞生长和 LPS 诱导的 MMP-2 和 MMP-13 表达。估计了不同支架中 SP600125 和 SB203580 的释放情况。使用 microCT 和组织学评估载药胶束纳米纤维对犬类 II 类分叉缺损的治疗效果。
然后，在静电纺丝过程中成功地将药物掺入明胶纤维中。我们证实，胶束具有球形结构，SP600125 胶束（SP-Ms）的平均粒径为 160nm，SB203580 胶束（SB-Ms）的平均粒径为 150nm。纳米纤维支架具有优异的包封能力、体外药物释放行为和细胞相容性。实时 PCR 和 Western blot 进一步表明，支架显著抑制了 LPS 诱导的 MMP-2 和 MMP-13 表达。
研究结果表明，本研究开发的双载药系统可能成为牙周病的一种高效治疗方法。
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