Interleukin-1 Receptor Antagonist: A New Therapy for Type 2 Diabetes Mellitus

被引:132
作者
Akash, Muhammad Sajid Hamid [1 ]
Shen, Qi [1 ]
Rehman, Kanwal [1 ]
Chen, Shuqing [1 ]
机构
[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol Toxicol & Biochem Pharmaceut, Hangzhou 310058, Zhejiang, Peoples R China
关键词
type 2 diabetes mellitus; IL-1Ra; drug delivery approaches; proinflammatory mediators; absorption; protein formulation; protein stability; protein delivery; control release/delivery; TUMOR-NECROSIS-FACTOR; BETA-CELL DYSFUNCTION; INDUCED INSULIN-RESISTANCE; ACTIVATED SIGNALING PATHWAYS; ELASTIN-LIKE POLYPEPTIDE; HIGH-FAT DIET; OXIDATIVE STRESS; FUSION PROTEIN; FACTOR-ALPHA; ISLET INFLAMMATION;
D O I
10.1002/jps.23057
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Various complex mechanisms and their multifactorial pathways decisively provoke low-grade local and systemic inflammation in beta-cells of pancreatic islets and peripheral tissues to induce beta-cells' dysfunction and apoptosis, insulin resistance, and ultimately, overt type 2 diabetes mellitus (T2DM). Conventional antidiabetic agents are being less popular, as they have some potential adverse effects. Currently, many anti-inflammatory therapeutic modalities are being investigated to abate the infuriating effects of inducers of T2DM and among them, interleukin-1 receptor antagonist (IL-1Ra) is the only one that has been approved by US Food and Drug Administration. We have compared IL-1Ra with other anti-inflammatory agents and conventional antidiabetic agents. Although, IL-1Ra has broad-spectrum anti-inflammatory activities, it also has some limitations due to its short half-life. To overcome the problem of short half-life of IL-1Ra, recently, we fused IL-1Ra in recombinant human serum albumin and expressed it in Pichia pastoris. Its bioactivity was also checked by IL-1-induced A375.S2 apoptotic cells. Furthermore, we have also formulated IL-1Ra with Pluronic F-127-based thermosensitive gel and investigated its in vitro characteristics to prolong its therapeutic effects. Further studies are required to investigate its therapeutic effects against diabetes and diabetes-associated complications. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101: 1647-1658, 2012
引用
收藏
页码:1647 / 1658
页数:12
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