Published 6 issues per year
ISSN Print: 0743-4863
ISSN Online: 2162-660X
Indexed in
Cracking the Junction: Update on the Progress of Gastrointestinal Absorption Enhancement in the Delivery of Poorly Absorbed Drugs
ABSTRACT
There are many challenges to the oral delivery of peptide-based drugs. In addition to overcoming issues relating to the metabolic stability of peptides and maximizing adherence and penetration through the mucus layer, new formulations to enhance absorption across the intestinal epithelium are required for effective delivery. The tight junctions between epithelial cells usually permit the flux of small hydrophilic drugs, while restricting the movement of larger hydrophilic drugs. Efforts to reversibly open tight junctions with paracellular permeability enhancers (PPE) have been shown to promote the absorption of larger molecules, including protein therapeutics. This review describes the proteins that comprise the tight junction and outlines various methods that have been explored to enhance class III solute absorption across this barrier, with particular attention to efforts to enhance oral peptide delivery. In particular, peptide-based PPEs are highlighted. Being proteins themselves, they potentially share physicochemical properties, diffusional characteristics, and stability issues with the therapeutic proteins being delivered. By understanding the mechanisms by which these PPEs act, analogues and peptidomimetics can be designed in order to safely enhance the delivery of biotech cargoes via the oral route.
-
Mohan H.M., Collins D., Maher S., Walsh E.G., Winter D.C., O’Brien P.J., Brayden D.J., Baird A.W., The mycotoxin patulin increases colonic epithelial permeability in vitro, Food and Chemical Toxicology, 50, 11, 2012. Crossref
-
Babiuch Krzysztof, Gottschaldt Michael, Werz Oliver, Schubert Ulrich S., Particulate transepithelial drug carriers: barriers and functional polymers, RSC Advances, 2, 28, 2012. Crossref
-
Wilcz-Villega Ewa M, McClean Siobhán, O’Sullivan Maria A, Mast Cell Tryptase Reduces Junctional Adhesion Molecule-A (JAM-A) Expression in Intestinal Epithelial Cells: Implications for the Mechanisms of Barrier Dysfunction in Irritable Bowel Syndrome, American Journal of Gastroenterology, 108, 7, 2013. Crossref
-
Jiang Lifang, Shen Chong, Dai Jing, Meng Qin, Di-rhamnolipids improve effect of trehalose on both hypothermic preservation and cryopreservation of rat hepatocytes, Applied Microbiology and Biotechnology, 97, 10, 2013. Crossref
-
Jiang Lifang, Long Xuwei, Meng Qin, Rhamnolipids enhance epithelial permeability in Caco-2 monolayers, International Journal of Pharmaceutics, 446, 1-2, 2013. Crossref
-
Edmonds David J., Price David A., , 48, 2013. Crossref
-
Wilcz-Villega E., McClean S., O'Sullivan M., Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS, Neurogastroenterology & Motility, 26, 3, 2014. Crossref
-
Dai Wei-Guo, Dong Liang C., Song Yanqiu, Enhanced bioavailability of poorly absorbed hydrophilic compounds through drug complex/in situ gelling formulation, International Journal of Pharmaceutics, 457, 1, 2013. Crossref
-
McClements David Julian, Xiao Hang, Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals, Food Funct., 5, 7, 2014. Crossref
-
Kliger Yossef, Computational approaches to therapeutic peptide discovery, Biopolymers, 94, 6, 2010. Crossref
-
Sjögren Erik, Abrahamsson Bertil, Augustijns Patrick, Becker Dieter, Bolger Michael B., Brewster Marcus, Brouwers Joachim, Flanagan Talia, Harwood Matthew, Heinen Christian, Holm René, Juretschke Hans-Paul, Kubbinga Marlies, Lindahl Anders, Lukacova Viera, Münster Uwe, Neuhoff Sibylle, Nguyen Mai Anh, Peer Achiel van, Reppas Christos, Hodjegan Amin Rostami, Tannergren Christer, Weitschies Werner, Wilson Clive, Zane Patricia, Lennernäs Hans, Langguth Peter, In vivo methods for drug absorption – Comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for formulation/API/excipient characterization including food effects, European Journal of Pharmaceutical Sciences, 57, 2014. Crossref
-
Bak Annette, Leung Dennis, Barrett Stephanie E., Forster Seth, Minnihan Ellen C., Leithead Andrew W., Cunningham James, Toussaint Nathalie, Crocker Louis S., Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—A Primer, The AAPS Journal, 17, 1, 2015. Crossref
-
Watkins J.B., Klaassen C.D., Absorption, Enterohepatic Circulation, and Fecal Excretion of Toxicants, in Comprehensive Toxicology, 2018. Crossref
-
Liu Yao, Liu Wei, Peng Qiu-Xian, Peng Jiang-Li, Yu Lin-Zhong, Hu Jian-Lan, Protective Effect of Huoxiang Zhengqi Oral Liquid on Intestinal Mucosal Mechanical Barrier of Rats with Postinfectious Irritable Bowel Syndrome Induced by Acetic Acid, Evidence-Based Complementary and Alternative Medicine, 2014, 2014. Crossref
-
McClements David Julian, Zou Liqiang, Zhang Ruojie, Salvia-Trujillo Laura, Kumosani Taha, Xiao Hang, Enhancing Nutraceutical Performance Using Excipient Foods: Designing Food Structures and Compositions to Increase Bioavailability, Comprehensive Reviews in Food Science and Food Safety, 14, 6, 2015. Crossref
-
Maher Sam, Leonard Thomas W., Jacobsen Jette, Brayden David J., Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic, Advanced Drug Delivery Reviews, 61, 15, 2009. Crossref
-
Maher Sam, Devocelle Marc, Ryan Sinéad, McClean Siobhán, Brayden David J., Impact of amino acid replacements on in vitro permeation enhancement and cytotoxicity of the intestinal absorption promoter, melittin, International Journal of Pharmaceutics, 387, 1-2, 2010. Crossref
-
Watkins J.B., Klaassen C.D., Absorption, Enterohepatic Circulation, and Fecal Excretion of Toxicants, in Comprehensive Toxicology, 2010. Crossref
-
Jones Lyn H., Price David A., , 52, 2013. Crossref
-
Maher Sam, Kennelly Rory, Bzik Victoria A., Baird Alan W., Wang Xuexuan, Winter Desmond, Brayden David J., Evaluation of intestinal absorption enhancement and local mucosal toxicity of two promoters. I. Studies in isolated rat and human colonic mucosae, European Journal of Pharmaceutical Sciences, 38, 4, 2009. Crossref
-
Nielsen Line Hagner, Nagstrup Johan, Gordon Sarah, Keller Stephan Sylvest, Østergaard Jesper, Rades Thomas, Müllertz Anette, Boisen Anja, pH-triggered drug release from biodegradable microwells for oral drug delivery, Biomedical Microdevices, 17, 3, 2015. Crossref
-
Moeller Eva Horn, Jorgensen Lene, Alternative routes of administration for systemic delivery of protein pharmaceuticals, Drug Discovery Today: Technologies, 5, 2-3, 2008. Crossref
-
McClements David Julian, Saliva-Trujillo Laura, Zhang Ruojie, Zhang Zipei, Zou Liqiang, Yao Mingfei, Xiao Hang, Boosting the bioavailability of hydrophobic nutrients, vitamins, and nutraceuticals in natural products using excipient emulsions, Food Research International, 88, 2016. Crossref
-
Bocsik Alexandra, Walter Fruzsina R., Gyebrovszki Andrea, Fülöp Lívia, Blasig Ingolf, Dabrowski Sebastian, Ötvös Ferenc, Tóth András, Rákhely Gábor, Veszelka Szilvia, Vastag Monika, Szabó-Révész Piroska, Deli Mária A., Reversible Opening of Intercellular Junctions of Intestinal Epithelial and Brain Endothelial Cells With Tight Junction Modulator Peptides, Journal of Pharmaceutical Sciences, 105, 2, 2016. Crossref
-
Zhang Ruojie, McClements David Julian, Enhancing nutraceutical bioavailability by controlling the composition and structure of gastrointestinal contents: Emulsion-based delivery and excipient systems, Food Structure, 10, 2016. Crossref
-
Salvia-Trujillo Laura, Martín-Belloso Olga, McClements David, Excipient Nanoemulsions for Improving Oral Bioavailability of Bioactives, Nanomaterials, 6, 1, 2016. Crossref
-
Ölander Magnus, Wiśniewski Jacek R., Matsson Pär, Lundquist Patrik, Artursson Per, The Proteome of Filter-Grown Caco-2 Cells With a Focus on Proteins Involved in Drug Disposition, Journal of Pharmaceutical Sciences, 105, 2, 2016. Crossref
-
Cheng Juan, Wu Zheng Hong, Ping Qineng Neng, Wang Bogang, Lu Junjun, The absorption characteristics of bifendate solid dispersion in rat intestinal tissue, Drug Development and Industrial Pharmacy, 36, 3, 2010. Crossref
-
Wright Ciara, Pilkington Ruth, Callaghan Máire, McClean Siobhán, Activation of MMP-9 by human lung epithelial cells in response to the cystic fibrosis-associated pathogen Burkholderia cenocepacia reduced wound healing in vitro, American Journal of Physiology-Lung Cellular and Molecular Physiology, 301, 4, 2011. Crossref
-
McClements David Julian, Xiao Hang, Demokritou Philip, Physicochemical and colloidal aspects of food matrix effects on gastrointestinal fate of ingested inorganic nanoparticles, Advances in Colloid and Interface Science, 246, 2017. Crossref
-
Terciolo Chloé, Dobric Aurélie, Ouaissi Mehdi, Siret Carole, Breuzard Gilles, Silvy Françoise, Marchiori Bastien, Germain Sébastien, Bonier Renaté, Hama Adel, Owens Roisin, Lombardo Dominique, Rigot Véronique, André Frédéric, Saccharomyces boulardii CNCM I-745 Restores intestinal Barrier Integrity by Regulation of E-cadherin Recycling, Journal of Crohn's and Colitis, 11, 8, 2017. Crossref
-
Cao Shu-jun, Xu Shuo, Wang Hui-ming, Ling Yong, Dong Jiahua, Xia Rui-dong, Sun Xiang-hong, Nanoparticles: Oral Delivery for Protein and Peptide Drugs, AAPS PharmSciTech, 20, 5, 2019. Crossref
-
Nielsen Hanne Mørck, Epithelial Permeation and Absorption Mechanisms of Biopharmaceuticals, in Mucosal Delivery of Biopharmaceuticals, 2014. Crossref
-
ElSawy Karim M., Lane David P., Verma Chandra S., Caves Leo S. D., Recognition Dynamics of p53 and MDM2: Implications for Peptide Design, The Journal of Physical Chemistry B, 120, 2, 2016. Crossref
-
Wang Hezhong, Roman Maren, Formation and Properties of Chitosan−Cellulose Nanocrystal Polyelectrolyte−Macroion Complexes for Drug Delivery Applications, Biomacromolecules, 12, 5, 2011. Crossref
-
Tan Yaw Sing, Spring David R., Abell Chris, Verma Chandra S., The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein–Protein Interactions, Journal of Chemical Theory and Computation, 11, 7, 2015. Crossref
-
ElSawy Karim M., Twarock Reidun, Verma Chandra S., Caves Leo S. D., Peptide Inhibitors of Viral Assembly: A Novel Route to Broad-Spectrum Antivirals, Journal of Chemical Information and Modeling, 52, 3, 2012. Crossref
-
Christfort Juliane Fjelrad, Strindberg Sophie, Al-khalili Shaimaa, Bar-Shalom Daniel, Boisen Anja, Nielsen Line Hagner, Müllertz Anette, In vitro and in vivo comparison of microcontainers and microspheres for oral drug delivery, International Journal of Pharmaceutics, 600, 2021. Crossref
-
Petersen Signe Beck, Nolan Gavin, Maher Sam, Rahbek Ulrik Lytt, Guldbrandt Mette, Brayden David J., Evaluation of alkylmaltosides as intestinal permeation enhancers: Comparison between rat intestinal mucosal sheets and Caco-2 monolayers, European Journal of Pharmaceutical Sciences, 47, 4, 2012. Crossref
-
ElSawy Karim M., Alminderej Fahad M., Verma Chandra S., Caves Leo S. D., Activating the p53 anti-cancer pathway by targeting the MDM2/MDMX dimer interface with short peptide segments: a computational peptide design experiment, Molecular Systems Design & Engineering, 7, 8, 2022. Crossref