Macrophage Targeting pH Responsive Polymersomes for Glucocorticoid Therapy
Macrophage Targeting pH Responsive Polymersomes for Glucocorticoid Therapy
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DOI：
10.3390/pharmaceutics11110614
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发表时间：
2019-11-01
期刊：
影响因子：
5.4
通讯作者：
Battaglia, Giuseppe
中科院分区：
文献类型：
--
作者：
Gouveia, Virginia M.;Rizzello, Loris;Battaglia, Giuseppe
糖皮质激素（GC）药物是治疗炎症性疾病的基础疗法。在这里，我们报告pH响应性聚（2-甲基丙烯酰氧基乙基磷酰胆碱）-聚（2-（二异丙基氨基）乙基甲基丙烯酸酯）（PMPC-PDPA）聚合物囊泡作为一个合适的纳米级载体，精确和可控地提供GC内发炎的靶细胞。体外细胞研究表明，聚合物囊泡确保了负载药物在巨噬细胞内的稳定性、选择性和生物利用度。在分子水平上，我们检测了关键的炎症相关标志物，如核因子-κ B、肿瘤坏死因子-α、白细胞介素-1 β和白细胞介素-6。由此，我们证明了pH响应性聚合物囊泡能够增强负载GC药物的抗炎作用。总的来说，我们证明了PMPC-PDPA聚合物囊泡有效促进炎症关闭的潜力，同时减少了基于GC的治疗中众所周知的治疗限制。
Glucocorticoid (GC) drugs are the cornerstone therapy used in the treatment of inflammatory diseases. Here, we report pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) polymersomes as a suitable nanoscopic carrier to precisely and controllably deliver GCs within inflamed target cells. The in vitro cellular studies revealed that polymersomes ensure the stability, selectivity and bioavailability of the loaded drug within macrophages. At molecular level, we tested key inflammation-related markers, such as the nuclear factor-kappa B, tumour necrosis factor-alpha, interleukin-1 beta, and interleukin-6. With this, we demonstrated that pH responsive polymersomes are able to enhance the anti-inflammatory effect of loaded GC drug. Overall, we prove the potential of PMPC-PDPA polymersomes to efficiently promote the inflammation shutdown, while reducing the well-known therapeutic limitations in GC-based therapy.