Ionic Liquids and Deep Eutectic Solvents for Enhanced Delivery of Antibodies in the Gastrointestinal Tract

被引:63
|
作者
Angsantikul, Pavimol [1 ]
Peng, Kevin [1 ]
Curreri, Alexander M. [1 ]
Chua, Ye [1 ]
Chen, Kevin Z. [1 ]
Ehondor, Jessica [1 ]
Mitragotri, Samir [1 ,2 ]
机构
[1] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA
关键词
ionic liquid; mAbs; monoclonal antibodies; oral delivery; stability; ORAL DELIVERY; PHARMACOKINETICS; PERMEABILITY; CHOLINE; HEALTH; MUCUS; ACID;
D O I
10.1002/adfm.202002912
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
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页数:11
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