The Fabrication of Polymeric Micelles Loaded Core-Shell Structured Nanofiber Mats and Their Effects on Anti-Inflammation in Vitro

doi:10.3969/j.issn.1005-4979.2018.03.002

Abstract

Abstract: Objective: The study aimed to assess and make a comparison between nanofiber mats encapsulated with three drug-loaded (SP600125, SB203580 and PD98059) polymeric micelles respectively on the anti-inflammatory effect in vitro. Methods: The drug-loaded micelles (SP-PMs, SB-PMs and PD-PMS) were prepared by the thin-film hydration method, and then encapsulated into nanofibers by using electrospinning technique. Cytotoxicity and the expression levels of inflammation-related genes MMP-2, MMP-9 as well as corresponding proteins were performed by periodontal ligament cells ( PDLCs). Results: The TEM images revealed the obtained nanofibers was line shape, and showed a narrow distribution range. The CLSM images verified that the drug-loaded micelles were encapsulated into nanofibers uniformly. The co-culturing of nanofiber mats and PDLCs demonstrated a good biocompatibility. In vitro anti-inflammation test illustrated that three drug-loaded nanofiber mats could both significantly decline the expression of MMP-2 and MMP-9 at gene and protein levels, and the inhibitory effects of SP-PMs and SB-PMs were better than PD-PMs group. Conclusion: The results suggested that SP-PMs or SB-PMs encapsulated nanofiber mat showed great anti-inflammatory effect in vitro. The present article presents an alternative technique that may be considered by periodontologists.

Key words: polymeric micelles loaded nanofiber mats, immunosuppressor, periodontitis, periodontal ligament cells, anti-inflammatory effect

摘要： 目的：研究分别负载免疫抑制剂（SP600125、SB203580和PD98059）聚合物胶束的纳米纤维膜，在体外对LPS（脂多糖）诱导的牙周膜细胞（periodontal ligament cells，PDLCs）的抗炎作用的影响，并进行比较。方法：通过薄膜水化法制备载药胶束（SP-PMs、SB-PMs、PD-PMs），并通过静电纺丝技术构建纳米纤维膜，使得免疫抑制剂负载其中。通过细胞学实验检测纳米纤维膜的生物相容性，和其对炎症相关基因及蛋白的表达影响。结果：扫描电镜显示纳米纤维呈线型结构，且纤维直径分布集中，激光共聚焦显示载药胶束负载于纤维中；细胞的增殖不受纳米纤维膜的影响；体外实验表明3种不同的载药纳米纤维膜均能抑制炎症因子的表达，其中负载SP-PMs、SB-PMs的纤维抗炎效果明显好于PD-PMs组。结论：负载SP-PMs或SB-PMs的纳米纤维膜显示出良好的抗炎效果，这为牙周炎的治疗提供了新的展望方向。

关键词: 载胶束纳米纤维膜, 免疫抑制剂, 牙周炎, 牙周膜细胞, 抗炎作用

CLC Number:

R782.4

LIU Xiao-Chen, SU Jian-Sheng. The Fabrication of Polymeric Micelles Loaded Core-Shell Structured Nanofiber Mats and Their Effects on Anti-Inflammation in Vitro[J]. 《Journal of Oral and Maxillofacial Surgery》, doi: 10.3969/j.issn.1005-4979.2018.03.002.

刘肖晨，苏俭生. 负载不同载药胶束纳米纤维膜的构建及其体外抗炎作用比较研究[J]. 《口腔颌面外科杂志》, doi: 10.3969/j.issn.1005-4979.2018.03.002.

/ / Recommend / Download Citations

URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.3969/j.issn.1005-4979.2018.03.002

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2018/V28/I3/127

References

[1] Intini G, Katsuragi Y, Kirkwood KL, et al. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions[J]. Adv Dent Res, 2014, 26(1):38-46.

[2] Yang WH, Kuo MYP, Liu CM, et al. Curcumin inhibits TGF1-induced CCN2 via Src, JNK, and Smad3 in gingiva[J]. J Dent Res, 2013, 92(7):629-634.

[3] Fan DP, Liu S, Jiang SC, et al. The use of SHP-2 gene transduced bone marrow mesenchymal stem cells to promote osteogenic differentiation and bone defect repair in rat[J]. J Biomed Mater Res Part A, 2016, 104(8):1871-1881.

[4] Wu HM, Fang L, Shen QY, et al. SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model[J]. Mol Immunol, 2015, 67(2 Pt B):311-316.

[5] Kwiecinska P, Roszkiewicz B, Lokociejewska M, et al. Elevated expression of NF-kappaB and Bcl-2 proteins in C2C12 myocytes during myogenesis is affected by PD98059, LY294002 and SB203580[J]. Cell Biol Int, 2005, 29(4):319-331.

[6] Rojewska E, Popiolek-Barczyk K, Kolosowska N, et al. PD98059 influences immune factors and enhances opioid analgesia in model of neuropathy[J]. PLoS One, 2015, 10(10):e0138583.

[7] Sun Y, Chen H, Ma S, et al. Administration of SB203580, a p38 MAPK inhibitor, reduced the expression of MMP9, and relieved neurologic severity in the experimental autoimmune neuritis (EAN) in rats[J]. Neurochem Res, 2015, 40(7):1410-1420.

[8] Sreekanth GP, Chuncharunee A, Sirimontaporn A, et al. SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation[J]. PLoS One, 2016, 11(2):e0149486.

[9] Liu YC, Lerner UH, Teng YT. Cytokine responses against periodontal infection: protective and destructive roles[J]. Periodontol 2000, 2010, 52(1):163-206.

[10] Sugano N. Biological plaque control: novel therapeutic approach to periodontal disease[J]. J Oral Sci, 2012, 54(1):1-5.

[11] Nath P, Eynott P, Leung SY, et al. Potential role of c-JunNH2-terminal kinase in allergic airway inflammation and remodelling: effects of SP600125[J]. Eur J Pharmacol, 2005, 506(3):273-283.

[12] Alibolandi M, Sadeghi F, Abnous K, et al. The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model[J]. Eur J Pharm Biopharm, 2015, 94:521-531.

[13] Nishiyama N, Kataoka K. Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery[J]. Pharmacol Ther, 2006, 112(3):630-648.

[14] Zhang Y, Zhang W, Johnston AH, et al. Comparison of the distribution pattern of PEG-b-PCL polymersomes delivered into the rat inner ear via different methods[J]. Acta Otolaryngol, 2011, 131(12):1249-1256.

[15] Cabral H, Matsumoto Y, Mizuno K, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size[J]. Nat Nanotechnol, 2011, 6(12):815-823.

[16] Sindhura Reddy N, Sowmya S, Bumgardner JD, et al. Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management[J]. Biochim Biophys Acta, 2014, 1840(6):2080-2090.

[17] Yang G, Wang J, Wang Y, et al. An implantable active-targeting micelle-in-nanofiber device for efficient and safe cancer therapy[J]. ACS nano, 2015, 9(2):1161-1174.

[18] Choi SH, Youn DY, Jo SM, et al. Micelle-mediated synthesis of single-crystalline beta(3C)-SiC fibers via emulsion electrospinning[J]. ACS Appl Mater Interfaces, 2011, 3(5):1385-1389.

[19] Elzoghby AO. Gelatin-based nanoparticles as drug and gene delivery systems: Reviewing three decades of research[J]. J Control Release, 2013, 172(3):1075-1091.

[20] Xiang P, Wang SS, He M, et al. The in vitro and in vivo biocompatibility evaluation of electrospun recombinant spider silk protein/PCL/gelatin for small caliber vascular tissue engineering scaffolds[J]. Colloids Surfaces B Biointerfaces, 2018, 163:19-28.

[21] Takahashi Y, Yamamoto M, Tabata Y. Enhanced osteoinduction by controlled release of bone morphogenetic protein-2 from biodegradable sponge composed of gelatin and beta-tricalcium phosphate[J]. Biomaterials, 2005, 26(23):4856-4865.

Please choose a citation manager

Content to export