Ionic Liquids and Deep Eutectic Solvents for Enhanced Delivery of Antibodies in the Gastrointestinal Tract
Ionic Liquids and Deep Eutectic Solvents for Enhanced Delivery of Antibodies in the Gastrointestinal Tract
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DOI：
10.1002/adfm.202002912
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发表时间：
2020-06-29
影响因子：
19
通讯作者：
Mitragotri, Samir
中科院分区：
文献类型：
--
作者：
Angsantikul, Pavimol;Peng, Kevin;Mitragotri, Samir
单克隆抗体 (mAb) 目前用于治疗多种疾病，包括癌症、牛皮癣、关节炎和特应性皮炎等。目前所有单克隆抗体均通过静脉内或皮下注射给药。在此，报道了使用新型离子液体和低共熔溶剂胆碱和乙醇酸盐（CGLY）作为治疗性抗体胃肠道给药的平台。 CGLY保持了TNFα抗体的稳定性和结构。 CGLY 显着增强体外 TNF α 抗体的旁细胞转运。 CGLY 还可以降低肠粘液的粘度，这是抗体转运的另一个关键障碍。大鼠体内结果表明，CGLY 有效地将 TNF α 抗体递送到肠粘膜以及体循环中。一周重复剂量研究随后进行的组织学和血清生化分析表明大鼠对 CGLY 具有良好的耐受性。总体而言，这项工作说明了使用基于胆碱的离子液体和低共熔溶剂作为口服递送平台来局部和全身递送治疗性抗体的前景。
Monoclonal antibodies (mAbs) are currently used for the treatment of numerous conditions including cancer, psoriasis, arthritis, and atopic dermatitis, among others. All mAbs are currently administered by either intravenous or subcutaneous injections. Herein, the use of a novel ionic liquid and deep eutectic solvent, choline and glycolate (CGLY), as a platform for gastrointestinal administration of therapeutic antibodies is reported. CGLY maintains the stability and structure of TNF alpha antibody. CGLY significantly enhances paracellular transport of TNF alpha antibody in vitro. CGLY also reduces the viscosity of the intestinal mucus, another key barrier for antibody transport. In vivo results in rats demonstrate that CGLY effectively delivers TNF alpha antibody into the intestinal mucosa as well as systemic circulation. One week repeat dose study followed by histology and serum biochemistry analysis indicates that CGLY is well tolerated by rats. Overall, this work illustrates the promise of using choline-based ionic liquids and deep eutectic solvents as an oral delivery platform for local as well as systemic delivery of therapeutic antibodies.