Lance Kevin D, Chatterjee Anuran, Wu Bian, Mottola Giorgio, Nuhn Harald, Lee Phin Peng, Sansbury Brian E, Spite Matthew, Desai Tejal A, Conte Michael S
UC Berkeley-UCSF Graduate Group in Bioengineering, San Francisco, California, 94158.
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, 94158.
J Biomed Mater Res A. 2017 Jan;105(1):31-41. doi: 10.1002/jbm.a.35861. Epub 2016 Aug 23.
Resolvin D1 (RvD1) belongs to a family of endogenously derived proresolving lipid mediators that have been shown to attenuate inflammation, activate proresolution signaling, and promote homeostasis and recovery from tissue injury. In this study we present a poly(lactic-co-glycolic acid) (PLGA) based thin-film device composed of layers of varying ratios of lactic and glycolic acid that elutes RvD1 unidirectionally to target tissues. The device demonstrated sustained release in vitro for 56 days with an initial burst of release over 14 days. The asymmetric design of the device released 98% of RvD1 through the layer with the lowest molar ratio of lactic acid to glycolic acid, and the remainder through the opposite side. We validated structural integrity of RvD1 released from the device by mass spectrometry and investigated its bioactivity on human vascular endothelial (EC) and smooth muscle cells (VSMC). RvD1 released from the device attenuated VSMC migration, proliferation, and TNF-α induced NF-κB activation, without evidence of cytotoxicity. Delivery of RvD1 to blood vessels was demonstrated ex vivo in a flow chamber system using perfused rabbit aortas and in vivo in a rat carotid artery model, with the devices applied as an adventitial wrap. Our results demonstrate a novel approach for sustained, local delivery of Resolvin D1 to vascular tissue at therapeutically relevant levels. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 31-41, 2017.
消退素D1（RvD1）属于内源性促消退脂质介质家族，已被证明可减轻炎症、激活促消退信号，并促进组织损伤后的内环境稳定和恢复。在本研究中，我们展示了一种基于聚乳酸-乙醇酸共聚物（PLGA）的薄膜装置，该装置由不同乳酸与乙醇酸比例的层组成，可将RvD1单向洗脱至靶组织。该装置在体外显示出持续释放56天，最初14天有一个释放高峰。该装置的不对称设计使98%的RvD1通过乳酸与乙醇酸摩尔比最低的层释放，其余部分通过相反侧释放。我们通过质谱法验证了从该装置释放的RvD1的结构完整性，并研究了其对人血管内皮细胞（EC）和平滑肌细胞（VSMC）的生物活性。从该装置释放的RvD1减弱了VSMC的迁移、增殖以及肿瘤坏死因子-α诱导的核因子-κB激活，且无细胞毒性证据。在体外，使用灌注兔主动脉的流动腔系统以及在体内大鼠颈动脉模型中，将该装置作为外膜包裹物应用，证明了RvD1可输送至血管。我们的结果展示了一种以治疗相关水平将消退素D1持续、局部递送至血管组织的新方法。© 2016威利期刊公司。《生物医学材料研究杂志》A部分：105A：31 - 41，2017年。
