Ionic Liquids and Deep Eutectic Solvents for Enhanced Delivery of Antibodies in the Gastrointestinal Tract,Advanced Functional Materials

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Ionic Liquids and Deep Eutectic Solvents for Enhanced Delivery of Antibodies in the Gastrointestinal Tract
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2020-06-29 , DOI: 10.1002/adfm.202002912
Pavimol Angsantikul ₁ , Kevin Peng ₁ , Alexander M. Curreri ₁ , Ye Chua ₁ , Kevin Z. Chen ₁ , Jessica Ehondor ₁ , Samir Mitragotri _{1,

2}

Affiliation

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 TNFα antibody. CGLY significantly enhances paracellular transport of TNFα 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 TNFα 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.

中文翻译：

用于增强胃肠道中抗体递送的离子液体和深共熔溶剂

单克隆抗体 (mAb) 目前用于治疗多种疾病，包括癌症、银屑病、关节炎和特应性皮炎等。目前，所有 mAb 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) 作为胃肠道给药治疗抗体的平台。CGLY 保持了 TNFα 抗体的稳定性和结构。CGLY 在体外显着增强 TNFα 抗体的细胞旁转运。CGLY 还降低了肠道粘液的粘度，这是抗体转运的另一个关键障碍。大鼠的体内结果表明 CGLY 有效地将 TNFα 抗体输送到肠粘膜和体循环中。一周重复剂量研究，随后进行组织学和血清生化分析，表明大鼠对 CGLY 耐受性良好。总的来说，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局部和全身性治疗性抗体口服给药平台的前景。

更新日期：2020-06-29

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