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Diffusion Of Drugs In Native And Purified Gastrointestinal Mucus.

A. Larhed, P. Artursson, J. Gråsjö, E. Björk
Published 1997 · Chemistry, Medicine

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The mucus layer covering the surface of the gastrointestinal tract may act as a barrier to drug absorption. The aim of this investigation was to study the self-diffusion coefficients of model drugs with different physicochemical properties in gastrointestinal mucus. An in vitro method was used to determine the self-diffusion coefficients of radiolabeled model drugs in different diffusion media. Glucosamine, mannitol, glucuronic acid, glucose, metoprotol, antipyrine, propranolol, hydrocortisone, and testosterone, which display large differences in charge and octanol/water distribution ratios (K), were used as model drugs. The diffusion coefficients of model drugs were compared in phosphate buffer (PB), native pig intestinal mucus (PIM), and purified pig gastric much (PPGM). PIM was not purified and therefore contained all the original components of native mucus, whereas PPGM contained only high molecular weight mucin molecules. Charge had only minor effects on the diffusion coefficients of the model drugs. Lipophilicity, however, had a much larger effect, the largest decrease in diffusion coefficient, 58%, was observed for testosterone in PIM. A negative relationship between the diffusion coefficient and log K was observed in PIM, but no relationship was observed in PPGM and PB. In contrast, the diffusion coefficients for two larger molecules of comparable size, the lipophilic peptide cyclosporin and the hydrophilic peptide D-arginine vasopressin, were markedly reduced in PIM. In conclusion, the most important physicochemical characteristic influencing the diffusion coefficient of most drugs in gastrointestinal mucus appears to be lipophilicity, whereas molecular size appears to have more influence for larger peptide drugs.
This paper references
10.1042/CS0700271
Diffusion of butyrate through pig colonic mucus in vitro.
G. Smith (1986)
Mucusmodelle zur Untersuchung von intestinalen Absorptionsmechanismen. I: Mitteilung : Validierung und Optimierung der Modelle
I. Matthes (1992)
10.1111/j.2042-7158.1990.tb06611.x
Diffusion coefficient in native mucus gel of rat small intestine
D. Winne (1990)
10.1016/0928-0987(95)00007-Z
Co-cultures of human intestinal goblet (HT29-H) and absorptive (Caco-2) cells for studies of drug and peptide absorption
A. Wikman-Larhed (1995)
10.1007/978-1-4615-9254-9_15
The structure and physiology of gastrointestinal mucus.
A. Allen (1982)
10.1042/BJ2110013
Isolation and characterization of human cervical-mucus glycoproteins.
I. Carlstedt (1983)
10.1016/0378-5173(93)90363-K
The mucus layer as a barrier to drug absorption in monolayers of human intestinal epithelial HT29-H goblet cells
J. Karlsson (1993)
10.1016/0021-9797(91)90039-B
Diffusion and interaction in gels and solutions: I. Method
L. Johansson (1991)
10.1111/j.2042-7158.1992.tb05461.x
Epi‐fluorescence Microscopy and Image Analysis Used to Measure Diffusion Coefficients in Gel Systems
B. T. Henry (1992)
10.1016/0378-5173(95)04120-6
The limiting role of mucus in drug absorption : drug permeation through mucus solution
P. G. Bhat (1995)
Mucusmodelle zur Untersuchung von intestinalen Absorptions-mechanismen. II: Mechanismen der Wechselwirkung von Wirkstoffen mit Intestinalmuccus
I. Matthes (1992)
10.1021/MA00022A019
Diffusion and interaction in gels and solutions. 3. Theoretical results on the obstruction effect
Lennart Johansson (1991)
10.1016/0014-2999(79)90231-0
Accumulation of drugs by resting or beating cardiac tissue.
H. Luellmann (1979)
10.1021/MA00022A018
Diffusion and interaction in gels and solutions. 2. Experimental results on the obstruction effect
Lennart Johansson (1991)
10.1016/0378-5173(90)90267-8
Absorption of a vasopressin analogue, 1-deamino-8-d-arginine-vasopressin (dDAVP), in a human intestinal epithelial cell line, CaCO-2
S. Lundin (1990)
Comparison of in vitro and in vivo models of drug transcytosis through the blood-brain barrier.
W. Pardridge (1990)
10.1097/00007691-198406000-00002
Cyclosporine: experience with therapeutic monitoring.
L. Bowers (1984)
10.1016/0378-5173(95)04333-0
Drug binding to gastric mucus glycoproteins
P. G. Bhat (1996)
10.1002/QSAR.19900090105
Drug lipophilicity in QSAR practice. I: A comparison of experimental with calculative approaches
R. Mannhold (1990)
10.1039/AN9911601113
Estimation of effective diffusion coefficients of model solutes through gastric mucus: assessment of a diffusion chamber technique based on spectrophotometric analysis.
M. Desai (1991)
10.1002/BDD.2510160502
Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals
T. Kararli (1995)
Mususmodelle zur Untersuchung von intestinalen Absorptionsmechanismen. III: Ein mathematisches Simulationsmodell der Wirkstoffdiffusion durch enteralen Mucus
A. Fahr (1992)
10.1016/0378-5173(84)90222-9
A theory of molecular diffusion in the intestinal mucus
N. Peppas (1984)
10.1146/ANNUREV.PH.57.030195.003025
The hydrophobic barrier properties of gastrointestinal mucus.
L. Lichtenberger (1995)
10.1039/AN9911600463
pH dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane-mounted glass pH electrode.
C. V. Nicholas (1991)
10.1016/0378-5173(86)90077-3
Binding of antibiotics to rat intestinal mucin
J. Niibuchi (1986)
10.1016/0378-5173(87)90116-5
The effects of mucus glycoproteins on the bioavailability of tetracycline. III. Everted gut studies
P. Kearney (1987)
10.1016/0304-4165(91)90027-E
The rheology of pig small intestinal and colonic mucus: weakening of gel structure by non-mucin components.
L. A. Sellers (1991)
10.1016/S0006-3495(94)80802-1
Antibody diffusion in human cervical mucus.
W. Saltzman (1994)



This paper is referenced by
10.1201/9780849359170-9
Physiological Parameters Relevant to Dissolution Testing: Hydrodynamic Considerations
S. Diebold (2005)
GASTRORETENTIVE DRUG DELIVERY SYSTEM Swapnil More *
K. Gavali (2018)
10.1016/j.jconrel.2018.11.023
Intestinal mucus is capable of stabilizing supersaturation of poorly water‐soluble drugs
Yan Yan Yeap (2019)
GASTRORETENTIVE DRUG DELIVERY SYSTEMS: A REVIEW ON EXPANDABLE SYSTEM
P. K. Wagh (2018)
10.1517/17425247.2015.1068287
Self-emulsifying drug delivery systems in oral (poly)peptide drug delivery
G. Leonavičiūtė (2015)
10.1039/c8sm02096e
Non-Gaussian, non-ergodic, and non-Fickian diffusion of tracers in mucin hydrogels.
Andrey G. Cherstvy (2019)
10.21276/APJHS.2016.3.4.22
GASTRORETENTIVE DRUG DELIVERY SYSTEM- A REVIEW
B. V. Reddy (2016)
10.1016/j.ijpharm.2013.05.040
Mucus as a barrier to lipophilic drugs.
H. Sigurdsson (2013)
10.1016/j.otc.2009.07.005
Local drug delivery.
R. Harvey (2009)
10.1016/j.addr.2017.11.001
Mucus models to evaluate the diffusion of drugs and particles.
J. Lock (2018)
ENHANCEMENT OF INTESTINAL ABSORPTION OF POORLY ABSORBED DRUGS BY USING VARIOUS PERMEATION ENHANCERS: AN OVERVIEW
Devendra Singh (2013)
10.1016/S0169-409X(01)00115-6
Drug transfer through mucus.
K. Khanvilkar (2001)
10.1016/B978-0-323-52725-5.00006-X
Nanometric Biopolymer Devices for Oral Delivery of Macromolecules with Clinical Significance
Sabyasachi Maiti (2017)
10.22270/JDDT.V2I3.164
ADVANCEMENTS IN CONTROLLED RELEASE GASTRORETENTIVE DRUG DELIVERY SYSTEM: A REVIEW
Ami Makwana (2012)
10.1016/S0169-409X(98)00037-4
The effect of physical barriers and properties on the oral absorption of particulates.
Norris (1998)
10.1016/j.ijpharm.2017.07.022
Tracing molecular and structural changes upon mucolysis with N-acetyl cysteine in human airway mucus.
B. Vukosavljevic (2017)
10.1016/j.addr.2017.10.014
A slippery slope: On the origin, role and physiology of mucus☆
Farhan Taherali (2018)
10.1016/J.JCIS.2003.09.040
Excluded volume effect of rat intestinal mucin on taurocholate/phosphatidylcholine mixed micelles.
T. Wiedmann (2004)
10.1016/J.EJPB.2005.07.008
Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant.
Shinya Takatsuka (2006)
Dietary fatty acids increase the absorption of toxic substances and drugs by modifying different absorption pathways in the intestinal epithelium
Bitte Aspenström-Fagerlund (2012)
Role of Melatonin, Neuropeptide S and Short Chain Fatty Acids in Regulation of Duodenal Mucosal Barrier Function and Motility
Wan Salman Wan Saudi (2015)
Review on Gastro Retentive Drug Delivery System
A. Badoni (2012)
10.2174/1568026013395100
Physicochemical Profiling (Solubility, Permeability and Charge State)
A. Avdeef (2001)
10.1016/J.IJPHARM.2004.11.028
The influence of excipients on the diffusion of ibuprofen and paracetamol in gastric mucus.
L. R. Shaw (2005)
10.1039/b811150b
Conditioning saliva for use in a microfluidic biosensor.
K. Helton (2008)
10.1016/j.addr.2008.09.006
Mathematical modeling of molecular diffusion through mucus.
Yen Cu (2009)
10.1021/LA0495130
Drying of films formed by ordered poly(ethylene oxide)-poly(propylene oxide) block copolymer gels.
Z. Gu (2005)
10.1016/J.CES.2009.04.050
Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents.
N. Peppas (2009)
10.1002/9783527636730.CH3
Oral Peptide Drug Delivery: Strategies to Overcome Challenges
Josias H. Hamman (2011)
10.1126/scitranslmed.aaf6413
An oral microjet vaccination system elicits antibody production in rabbits
Kiana Aran (2017)
10.1002/JPS.20882
Enhancing absorption of fluorescein and LHRH across hindgut epithelia in a marsupial, the common brushtail possum Trichosurus vulpecula.
J. Wen (2007)
10.1016/j.ijpharm.2013.04.002
Comparative study of Pluronic(®) F127-modified liposomes and chitosan-modified liposomes for mucus penetration and oral absorption of cyclosporine A in rats.
Dan Chen (2013)
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