Resveratrol Delivery from Porous Poly(lactide-co-glycolide) Scaffolds Promotes an Anti-Inflammatory Environment within Visceral Adipose Tissue
Resveratrol Delivery from Porous Poly(lactide-co-glycolide) Scaffolds Promotes an Anti-Inflammatory Environment within Visceral Adipose Tissue
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DOI：
10.1021/acsami.8b13421
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发表时间：
2018-12-19
影响因子：
9.5
通讯作者：
Gower, R. Michael
中科院分区：
文献类型：
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作者：
Murphy, Kendall P.;Hendley, Michael A.;Gower, R. Michael
随着生物材料疗法的出现，以解决脂肪组织功能障碍，代谢疾病的基础，必须建立对这些系统的免疫反应。作为一种潜在的治疗方法，我们正在研究白藜芦醇从多孔聚（丙交酯-共-乙交酯）支架设计整合与脂肪组织。选择白藜芦醇是因为它能够保护小鼠和灵长类动物免受高脂肪饮食和广泛的抗炎特性。在此，我们报道了具有高白藜芦醇负载的支架的制造，其稳定且活性长达一年。体外释放曲线表明，药物释放是双相的，在3天内爆发释放，然后是平台期。令人惊讶的是，我们发现植入小鼠脂肪组织中的PLG支架促进了抗炎环境，其特征在于与未处理过的脂肪相比，高TNF-1和低TNF-α和IL-6。从支架递送白藜芦醇通过减少植入部位的单核细胞和淋巴细胞数量并增加IL-10和IL-13（促进健康脂肪组织的细胞因子）的表达来增强这种抗炎环境。在治疗应用方面，植入旨在将白藜芦醇释放到内脏脂肪中的支架，降低了喂食高脂肪饮食的小鼠中MCP-1的表达，MCP-1是一种在肥胖期间驱动局部和全身炎症的分子。总之，使用聚（丙交酯-共-乙交酯）支架将白藜芦醇递送至脂肪组织是治疗驱动代谢疾病的脂肪组织炎症的有前景的治疗策略。
As biomaterial therapies emerge to address adipose tissue dysfunction that underlies metabolic disease, the immune response to these systems must be established. As a potential therapy, we are investigating resveratrol delivery from porous poly(lactide-co-glycolide) scaffolds designed to integrate with adipose tissue. Resveratrol was selected for its ability to protect mice and primates from high fat diet and broad anti-inflammatory properties. Herein, we report fabrication of scaffolds with high resveratrol loading that are stable and active for up to one year. In vitro release profiles indicate that drug release is biphasic with a burst release over 3 days followed by a plateau. Surprisingly, we find that PLG scaffolds implanted into adipose tissue of mice promote an anti-inflammatory environment characterized by high arginase-1 and low TNF-alpha and IL-6 compared to naive unmanipulated fat. Resveratrol delivery from the scaffold augments this anti-inflammatory environment by decreasing monocyte and lymphocyte numbers at the implant site and increasing expression of IL-10 and IL-13, cytokines that promote healthy adipose tissue. In terms of therapeutic applications, implant of scaffolds designed to release resveratrol into the visceral fat decreases MCP-1 expression in mice fed a high fat diet, a molecule that drives both local and systemic inflammation during obesity. Taken together, resveratrol delivery to adipose tissue using poly(lactide-co-glycolide) scaffolds is a promising therapeutic strategy for the treatment of adipose tissue inflammation that drives metabolic disease.