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

被引：77

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

来源：

ADVANCED FUNCTIONAL MATERIALS | 2021年 / 31卷 / 44期

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.

引用

页数：11

共 54 条

[21] Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers [J].

Ghaffarian, Rasa ;

Muro, Silvia .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2013, (80) :e50638

[22]

Green SJ, 2006, GUT, V55, P1681

[23] Permeation of Insulin, Calcitonin and Exenatide across Caco-2 Monolayers: Measurement Using a Rapid, 3-Day System [J].

Gupta, Vivek ;

Doshi, Nishit ;

Mitragotri, Samir .

PLOS ONE, 2013, 8 (02)

[24] AVX-470, an Orally Delivered Anti-Tumour Necrosis Factor Antibody for Treatment of Active Ulcerative Colitis: Results of a First-in-Human Trial [J].

Harris, M. Scott ;

Hartman, Deborah ;

Lemos, Brenda R. ;

Erlich, Emma C. ;

Spence, Sharon ;

Kennedy, Sally ;

Ptak, Theadore ;

Pruitt, Ronald ;

Vermeire, Severine ;

Fox, Barbara S. .

JOURNAL OF CROHNS & COLITIS, 2016, 10 (06) :631-640

[25] Novel complexation hydrogels for oral peptide delivery:: In vitro evaluation of their cytocompatibility and insulin-transport enhancing effects using Caco-2 cell monolayers [J].

Ichikawa, H ;

Peppas, NA .

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2003, 67A (02) :609-617

[26] Biotherapeutics: Challenges and Opportunities for Predictive Toxicology of Monoclonal Antibodies [J].

Johnson, Dale E. .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (11)

[27] Targeted localized use of therapeutic antibodies: a review of non-systemic, topical and oral applications [J].

Jones, Russell G. A. ;

Martino, Angela .

CRITICAL REVIEWS IN BIOTECHNOLOGY, 2016, 36 (03) :506-520

[28] Circular Dichroism Spectroscopy as a Tool for Monitoring Aggregation in Monoclonal Antibody Therapeutics [J].

Joshi, Varsha ;

Shivach, Tarun ;

Yadav, Nitin ;

Rathore, Anurag S. .

ANALYTICAL CHEMISTRY, 2014, 86 (23) :11606-11613

[29] Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies [J].

Keizer, Ron J. ;

Huitema, Alwin D. R. ;

Schellens, Jan H. M. ;

Beijnen, Jos H. .

CLINICAL PHARMACOKINETICS, 2010, 49 (08) :493-507

[30] Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells [J].

Konsoula, R ;

Barile, FA .

TOXICOLOGY IN VITRO, 2005, 19 (05) :675-684

← 1 2 3 4 5 6 →