Abstract
The development of oral insulin using the eligen(®) technology represents a significant advance in insulin administration which is expected to improve the quality of life of diabetic patients. As clinical studies progress, a great deal of interest has focused on the process by which this technology enables insulin absorption from the intestinal lumen into the bloodstream. The eligen(®) technology employs low molecular weight compounds (termed drug delivery agents or carriers) which interact weakly and non-covalently with insulin, increasing its lipophilicity and thereby its ability to cross the gastrointestinal epithelium. In this study we investigated the mechanism of insulin absorption across caco-2 cell monolayers with one of these drug delivery agents, N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC). Our results show that SNAC increases insulin permeability approximately ten fold across cell monolayers and does so without affecting mannitol permeability or disrupting cell membranes. Confocal microscopy and immunocytochemistry revealed that insulin is transported transcellularly without detectable alteration of the tight junctions between adjacent cells. SNAC also appears to play some role in protecting insulin from proteolytic degradation, potentially allowing for more intact insulin to be available at the site of absorption.
Keywords: oral insulin, caco-2 cells, transcellular absorption, occludin, circular dichroism
Current Drug Delivery
Title: Oral Delivery of Insulin with the eligen(®) Technology: Mechanistic Studies
Volume: 2 Issue: 2
Author(s): Dmitry Malkov, Robert Angelo, Huai-zhen Wang, Elizabeth Flanders, Heather Tang and Isabel Gomez-Orellana
Affiliation:
Keywords: oral insulin, caco-2 cells, transcellular absorption, occludin, circular dichroism
Abstract: The development of oral insulin using the eligen(®) technology represents a significant advance in insulin administration which is expected to improve the quality of life of diabetic patients. As clinical studies progress, a great deal of interest has focused on the process by which this technology enables insulin absorption from the intestinal lumen into the bloodstream. The eligen(®) technology employs low molecular weight compounds (termed drug delivery agents or carriers) which interact weakly and non-covalently with insulin, increasing its lipophilicity and thereby its ability to cross the gastrointestinal epithelium. In this study we investigated the mechanism of insulin absorption across caco-2 cell monolayers with one of these drug delivery agents, N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC). Our results show that SNAC increases insulin permeability approximately ten fold across cell monolayers and does so without affecting mannitol permeability or disrupting cell membranes. Confocal microscopy and immunocytochemistry revealed that insulin is transported transcellularly without detectable alteration of the tight junctions between adjacent cells. SNAC also appears to play some role in protecting insulin from proteolytic degradation, potentially allowing for more intact insulin to be available at the site of absorption.
Export Options
About this article
Cite this article as:
Malkov Dmitry, Angelo Robert, Wang Huai-zhen, Flanders Elizabeth, Tang Heather and Gomez-Orellana Isabel, Oral Delivery of Insulin with the eligen(®) Technology: Mechanistic Studies, Current Drug Delivery 2005; 2 (2) . https://dx.doi.org/10.2174/1567201053586001
DOI https://dx.doi.org/10.2174/1567201053586001 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Antioxidant Properties and Glucose Uptake Effect of Ethanol Extracts from Different Sweet Potato Leaves Prepared by Lyophilization and Oven- Drying at 40 °C
Current Nutrition & Food Science Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery The Role of Insulin Receptor Isoforms and Hybrid Insulin/IGF-I Receptors in Human Cancer
Current Pharmaceutical Design Beyond Hemostasis: The Role of Platelets in Inflammation, Malignancy and Infection
Cardiovascular & Hematological Disorders-Drug Targets Evidence-Based Review of Physiologic Effects of Kangaroo Care
Current Women`s Health Reviews Translating Pharmacogenetics and Pharmacogenomics: The Last 60 Years and the Rise of Collective Innovation as a Force Multiplier for Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Pathophysiology of the Vascular Wall and its Relevance for Cerebrovascular Disorders in Aged Rodents
Current Neurovascular Research Nanosized Tamoxifen-Porphyrin-Glucose [TPG] Conjugate: Novel Selective Anti-breast-cancer Agent, Synthesis and In Vitro Evaluations
Medicinal Chemistry The Mechanistic Target of Rapamycin (mTOR): Novel Considerations as an Antiviral Treatment
Current Neurovascular Research The Allosteric Site for the Nascent Cell Wall in Penicillin-Binding Protein 2a: An Achilles’ Heel of Methicillin-Resistant Staphylococcus aureus
Current Medicinal Chemistry Redox Regulation of Fertility in Aging Male and the Role of Antioxidants: A Savior or Stressor
Current Pharmaceutical Design Naringin Inhibits TNF-α Induced Oxidative Stress and Inflammatory Response in HUVECs via Nox4/NF-κ B and PI3K/Akt Pathways
Current Pharmaceutical Biotechnology The Effect of Levothyroxine in Comparison with Placebo on Serum Osteocalcin Levels in Patients with Subclinical Hypothyroidism
Current Drug Safety PREFACE
Endocrine, Metabolic & Immune Disorders - Drug Targets Hypoglycemia and Glucocorticoid-free Immunosuppression are Related With Low Dehydroepiandrosterone Sulfate Level
Endocrine, Metabolic & Immune Disorders - Drug Targets NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor as a Potential Drug Target
Current Drug Targets Therapeutic Strategies of Plant-derived Compounds for Diabetes Via Regulation of Monocyte Chemoattractant Protein-1
Current Medicinal Chemistry Network Effect of Wt-mutant p53 Interactions and Implications on p53 Gene Therapy
Current Pharmaceutical Design Safety and Effectiveness of Compounded Galenic Cholic Acid for Bile Acid Synthesis Disorder: A Case Report
Endocrine, Metabolic & Immune Disorders - Drug Targets Imaging as a Strategy for Premortem Diagnosis and Staging of Tauopathies
Current Alzheimer Research