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Chitosans As Absorption Enhancers Of Poorly Absorbable Drugs. 3: Influence Of Mucus On Absorption Enhancement.

N. G. Schipper, K. M. Vårum, P. Stenberg, G. Ocklind, H. Lennernäs, P. Artursson
Published 1999 · Chemistry, Medicine

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Chitosans are potent nontoxic absorption enhancers after nasal administration but their effects on the intestinal epithelium in vivo has not been studied in detail. In this study, the effects of chitosans with varying molecular weights and degrees of acetylation on the absorption of a poorly absorbed model drug (atenolol) were studied in intestinal epithelial cell layers with or without a mucus layer and in an in situ perfusion model of rat ileum. The effects of the chitosans on epithelial morphology and release of lactate dehydrogenase (LDH) into the perfusate were investigated in the in situ model. The chitosans had pronounced effects on the permeability of mucus-free Caco-2 layers and enhanced the permeation of atenolol 10- to 15-fold, with different absorption kinetics for different chitosans, in accordance with previous results. In contrast, enhancement of atenolol absorption through rat ileum was modest. LDH release from the tissues perfused with chitosans did not increase, indicating that the chitosans were used at nontoxic concentrations. Morphological examination of the perfused ileal tissues revealed more mucus discharge from the tissues exposed to chitosans than from controls, which suggested that the discharged mucus may inhibit the binding of chitosan to the epithelial surface and hence decrease the absorption-enhancing effect. This hypothesis was supported by studies with intestinal epithelial HT29-H goblet cells covered with a mucus layer. The binding of chitosan to the epithelial cell surface and subsequent absorption-enhancing effects were significantly reduced in mucus-covered HT29-H cultures. When the mucus layer was removed prior to the addition of chitosan, the cell surface binding and absorption-enhancing effects of the chitosans were increased. We conclude that the modest absorption-enhancing effects of unformulated chitosan solutions in the perfused rat ileum are a result of the mucus barrier in this tissue. This effect may be overcome by increasing the local concentrations of both chitosan and drug, i.e,. through formulation of the chitosan into a particulate dosage form.
This paper references
Cell cultures as models for drug absorption across the intestinal mucosa.
P. Artursson (1991)
Water-solubility of partially N-acetylated chitosans as a function of pH: effect of chemical composition and depolymerisation
K. M. Vårum (1994)
Strong ionic interactions between mucins and two basic proteins, mucus proteinase inhibitor and lysozyme, in human bronchial secretions.
I. Van-Seuningen (1992)
Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals
T. Kararli (1995)
Diffusion of drugs in native and purified gastrointestinal mucus.
A. Larhed (1997)
Interaction of LS174T human colon cancer cell mucins with Entamoeba histolytica: an in vitro model for colonic disease.
A. Belley (1996)
The thickness of the mucus layer in different segments of the rat intestine
L. Szentkuti (2004)
Development of intestinal cell culture models for drug transport and metabolism studies
A. Quaroni (1996)
Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells.
P. Artursson (1990)
Some non-mucin components of mucus and their possible biological roles.
J. Clamp (1984)
The effect of gastro-intestinal mucus on drug absorption
A. Macadam (1993)
Carrier mediated transport of amino acids, small peptides, and their drug analogs
P. Sinko (1987)
Compositional heterogeneity of heterogeneously deacetylated chitosans
Mette H. Ottey (1996)
Advancing quantitative and mechanistic approaches in interfacing gastrointestinal drug absorption studies in animals and humans
N. Ho (1983)
Quantitative mechanistic studies in simultaneous fluid flow and intestinal absorption using steroids as model solutes
I. Komiya (1980)
Absorptive and mucus-secreting subclones isolated from a multipotent intestinal cell line (HT-29) provide new models for cell polarity and terminal differentiation
C. Huet (1987)
Sedimentation analysis of potential interactions between mucins and a putative bioadhesive polymer
I. Fiebrig (1994)
Degradation of fully water-soluble, partially N-acetylated chitosans with lysozyme
Ragnhild J. Nordtveit (1994)
Solution properties of chitosans: conformation and chain stiffness of chitosans with different degrees of N-acetylation
M. Anthonsen (1993)
The interactions between highly de-N-acetylated chitosans and lysozyme from chicken egg white studied by 1H-NMR spectroscopy.
A. Kristiansen (1998)
Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells.
P. Artursson (1991)
Improved High‐Performance Liquid Chromatography Assay for Atenolol in Plasma and Urine Using Fluorescence Detection
R. Morris (1991)
Co-cultures of human intestinal goblet (HT29-H) and absorptive (Caco-2) cells for studies of drug and peptide absorption
A. Wikman-Larhed (1995)
Differentiation-associated antimicrobial functions in human colon adenocarcinoma cell lines.
M. Bernet-Camard (1996)

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Passive permeability and active transport models for the prediction of oral absorption
P. Artursson (2007)
Approaches for enhancing oral bioavailability of peptides and proteins.
J. Renukuntla (2013)
The Role of Chitosan in Drug Delivery
A. Fini (2003)
Thiolated Chitosans: Novel Polymers for Mucoadhesive Drug Delivery – A Review
S. Sreenivas (2008)
Nanoparticles in Different Delivery Systems: A Brief Review
Anubhav Nagal (2013)
Approaches to improve intestinal and transmucosal absorption of peptide and protein drugs.
A. Yamamoto (2020)
Antioxidant properties of high molecular weight dietary chitosan in vitro and in vivo
M. Anraku (2011)
Tracing transport of chitosan nanoparticles and molecules in Caco-2 cells by fluorescent labeling
X. Jia (2009)
Hollow and degradable polyelectrolyte nanocapsules for protein drug delivery.
Shujun Shu (2010)
Bioavailability enhancement of glucosamine hydrochloride by chitosan.
S. Qian (2013)
Recent Advancements in Research on Chitin and Chitosan Derivatives for Drug Delivery Application
Thandapani Gomathi (2014)
Chitosan—A versatile semi-synthetic polymer in biomedical applications
M. Dash (2011)
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Guanyu Chen (2018)
Chitosan: A promising therapeutic agent and effective drug delivery system in managing diabetes mellitus.
S. Sarkar (2020)
Chitosan-based hydrogels for nasal drug delivery: from inserts to nanoparticles
B. Luppi (2010)
Chitosan and its derivatives: potential excipients for peroral peptide delivery systems.
A. Bernkop-Schnürch (2000)
Nasal insulin delivery in the chitosan solution: in vitro and in vivo studies.
Shaoyun Yu (2004)
20 Nasal Delivery of Peptide Drugs
D. Pillion (2006)
An insight on hyaluronic acid in drug targeting and drug delivery
A. Yadav (2008)
Chitosan as biomaterial in drug delivery and tissue engineering.
Saad M Ahsan (2018)
In vivo and in vitro characterization of novel microparticulates based on hyaluronan and chitosan hydroglutamate
St Lim (2008)
Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells.
Jing Wen Loh (2012)
Effect of Rhamnolipids on Permeability Across Caco-2 Cell Monolayers
Charity J. Wallace (2013)
Models to predict intestinal absorption of therapeutic peptides and proteins.
Filipa Antunes (2013)
Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer.
H. Pae (2001)
Methylated N-(4-N,N-Dimethylaminobenzyl) Chitosan, a Novel Chitosan Derivative, Enhances Paracellular Permeability Across Intestinal Epithelial Cells (Caco-2)
Jariya Kowapradit (2008)
Physicochemical and Immunological Characterization of N,N,N-Trimethyl Chitosan-Coated Whole Inactivated Influenza Virus Vaccine for Intranasal Administration
N. Hagenaars (2009)
Orally Administered Therapeutic Peptide Delivery: Enhanced Absorption Through the Small Intestine Using Permeation Enhancers
V. Pillay (2012)
Biocompatibility of Chitosan Carriers with Application in Drug Delivery
S. Rodrigues (2012)
Genotoxicity evaluation of stearic acid grafted chitosan oligosaccharide nanomicelles.
Peng Hu (2013)
Application of natural and semi-synthetic polymers for the delivery of sensitive drugs
Oliver Germershaus (2015)
Ramkumar Ponnuraj (2015)
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