IL-1Ra and its Delivery Strategies: Inserting the Association in Perspective
IL-1Ra and its Delivery Strategies: Inserting the Association in Perspective
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DOI：
10.1007/s11095-013-1118-0
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发表时间：
2013-11-01
影响因子：
3.7
通讯作者：
Chen, Shuqing
中科院分区：
文献类型：
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作者：
Akash, Muhammad Sajid Hamid;Rehman, Kanwal;Chen, Shuqing
白细胞介素-1受体拮抗剂（IL-1 Ra）是天然存在的促炎细胞因子白细胞介素-1家族的抗炎拮抗剂。IL-1 Ra的广谱抗炎作用已被研究用于多种自身免疫性疾病，如糖尿病、类风湿性关节炎。尽管IL-1 Ra具有显著的广谱抗炎作用，但其生物半衰期较短（4-6 h），为了科普这一问题，迄今为止，已经应用了许多递送策略来延长IL-1 Ra的半衰期和/或延长IL-1 Ra从其靶位点的稳态持续释放。在本文中，我们概述了所有试图延长IL-1 Ra治疗效果持续时间的方法，包括使用融合蛋白技术融合IL-1 Ra以延长半衰期和/或使用各种可生物降解聚合物开发新剂型以延长其在给药部位的稳态持续释放。这些方法的特征在于它们对IL-1 Ra的体外释放特性和/或药代动力学和药效学参数的预期影响。我们还比较了这些递送策略与彼此的基础上的生物活性的IL-1 Ra融合蛋白伴侣和/或封装与可生物降解的聚合物后。
Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory antagonist of interleukin-1 family of pro-inflammatory cytokines. The broad spectrum anti-inflammatory effects of IL-1Ra have been investigated against various auto-immune diseases such as diabetes mellitus, rheumatoid arthritis. Despite of its outstanding broad spectrum anti-inflammatory effects, IL-1Ra has short biological half-life (4-6 h) and to cope with this problem, up till now, many delivery strategies have been applied either to extend the half-life and/or prolong the steady-state sustained release of IL-1Ra from its target site. Here in our present paper, we have provided an overview of all approaches attempted to prolong the duration of therapeutic effects of IL-1Ra either by fusing IL-1Ra using fusion protein technology to extend the half-life and/or development of new dosage forms using various biodegradable polymers to prolong its steady-state sustained release at the site of administration. These approaches have been characterized by their intended impact on either in vitro release characteristics and/or pharmacokinetic and pharmacodynamic parameters of IL-1Ra. We have also compared these delivery strategies with each other on the basis of bioactivity of IL-1Ra after fusion with fusion protein partner and/or encapsulation with biodegradable polymer.