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新型英夫利昔单抗聚氨酯纳米颗粒可减少体外肠上皮屏障模型中的炎症反应。

Novel polyurethane-based nanoparticles of infliximab to reduce inflammation in an in-vitro intestinal epithelial barrier model.

机构信息

School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland.

Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, Italy.

出版信息

Int J Pharm. 2019 Jun 30;565:533-542. doi: 10.1016/j.ijpharm.2019.05.025. Epub 2019 May 11.

Abstract

In this study we examined the potential of novel biodegradable polymers of polyesterurethane (PU), and its PEGylated (PU-PEG) form as nanocarriers of Infliximab (INF), to treat inflammation in an in-vitro epithelial model. Nanoparticles (NPs) formulated were of average size of 200-287 nm. INF loading of NPs (INF-NPs) resulted in an increase in size and zeta potential. No cytotoxicity was observed for any of the NPs. Cellular interaction and uptake of PU NPs were similar compared with polycaprolactone (PCL) NPs and significantly higher to Poly(lactic-co-glycolic) acid (PLGA) NPs. Cellular interaction was higher for corresponding PEG-NPs. INF-PU and INF-PU-PEG NPs showed a rapid rate and extent of recovery of the epithelial barrier function in inflamed Caco-2 cell monolayers and decreased cytokine levels in inflamed monocytes. Results obtained in this study are promising and the potential of PU and PU-PEG NPs for drug delivery and targeting to treat gastrointestinal inflammation warrants further investigation.

摘要

在这项研究中,我们研究了新型可生物降解聚酯聚氨酯(PU)及其聚乙二醇化(PU-PEG)形式的聚合物作为英夫利昔单抗(INF)纳米载体的潜力,以治疗体外上皮模型中的炎症。所制备的纳米颗粒(NPs)的平均粒径为 200-287nm。纳米颗粒(INF-NPs)的 INF 负载导致粒径和zeta 电位增加。任何 NPs 都没有观察到细胞毒性。与聚己内酯(PCL)纳米颗粒相比,PU 纳米颗粒的细胞相互作用和摄取相似,与聚乳酸-共-羟基乙酸(PLGA)纳米颗粒相比显著更高。相应的 PEG-NPs 的细胞相互作用更高。INF-PU 和 INF-PU-PEG NPs 显示出在炎症 Caco-2 细胞单层中上皮屏障功能快速恢复的速率和程度,并降低了炎症单核细胞中的细胞因子水平。本研究的结果很有希望,PU 和 PU-PEG NPs 具有用于药物输送和靶向治疗胃肠道炎症的潜力,值得进一步研究。

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