Mathematical modeling of molecular diffusion through mucus

Advanced Drug Delivery Reviews

Volumn 61, Issue 2, 2009, Pages 101-114

  Cu, Yen ^a   Saltzman, W Mark ^a  

^a Yale University   (United States)

Author keywords

Diffusion in gel; Drug delivery; Imaging; Mass transport; Mucosa; Particles

Indexed keywords

DIFFUSION IN GEL; IMAGING; MASS TRANSPORT; MUCOSA; PARTICLES;

BODY FLUIDS; DIFFUSION; DIFFUSION IN LIQUIDS; DIFFUSION IN SOLIDS; DRUG DELIVERY; GELATION; GELS; MASS TRANSFER; MATHEMATICAL TECHNIQUES; MODELS; PHYSICAL CHEMISTRY; TRANSPORTATION ROUTES;

MATHEMATICAL MODELS;

DIFFUSION; DIFFUSION COEFFICIENT; DRUG DELIVERY SYSTEM; EPITHELIUM; GEL; HYDRODYNAMICS BASED TRANSFECTION; LIGHT SCATTERING; MATHEMATICAL MODEL; MUCUS; PARTICLE SIZE; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; SCANNING ELECTRON MICROSCOPY; VISCOELASTICITY;

ANIMALS; DIFFUSION; HUMANS; MACROMOLECULAR SUBSTANCES; MODELS, BIOLOGICAL; MODELS, THEORETICAL; MUCUS; PHYSICOCHEMICAL PHENOMENA; VISCOSITY;

EID: 60349123660     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2008.09.006     Document Type: Review

References (116)

1. Creeth J.M. Constituents of mucus and their separation. Br. Med. Bull. 34 (1978) 17-24
2. Norris D.A., Puri N., and Sinko P.J. The effect of physical barriers and properties on the oral absorption of particulates. Adv. Drug Deliv. Rev. 34 (1998) 135-154
3. Lee S.P., and Nicholls J.F. Diffusion of charged ions in mucus gel: effect of net charge. Biorheology 24 (1987) 565-569
4. Khanvilkar K., Donovan M.D., and Flanagan D.R. Drug transfer through mucus. Adv. Drug Deliv. Rev. 48 (2001) 173-193
5. Allen A., Leonard A.J., and Sellers L.A. The mucus barrier. Its role in gastroduodenal mucosal protection. J. Clin. Gastroenterol. 10 Suppl 1 (1988) S93-98
6. Lamont J.T. Mucus: the front line of intestinal mucosal defense. Ann. N. Y. Acad. Sci. 664 (1992) 190-201
7. Litt M. Comparative studies of mucus and mucin physiochemistry. In: Nugent J., and O'Connor M. (Eds). Mucus and mucosa (1984), Pitman, London 196-206
8. Cone R. In: Ogra P.L., Mestecky J., Lamm M.E., Strober W., Bienenstock J., and McGhee J.R. (Eds). Mucosal Immunology (1999), Academic Press, San Diego 43-66
9. Carlstedt I., and Sheehan J.K. Macromolecular properties and polymeric structure of mucus glycoproteins. Ciba Found. Symp. 109 (1984) 157-172
10. Shogren R., Gerken T.A., and Jentoff J. Role of glycosylation on the conformation and chain dimensions of O-linked glycoproteins: light-scattering studies of ovine submaxillary mucin. Biochemistry 28 (1989) 5525-5536
11. Thornton D.J., and Sheehan J.K. From mucins to mucus: toward a more coherent understanding of this essential barrier. Proc. Am. Thorac. Soc. 1 (2004) 54-61
12. Saltzman W.M., Radomsky M.L., Whaley K.J., and Cone R.A. Antibody diffusion in human cervical mucus. Biophys. J. 66 (1994) 508-515
13. Larhed A.W., Artursson P., and Bjork E. The influence of intestinal mucus components on the diffusion of drugs. Pharm. Res. 15 (1998) 66-71
14. Bell A.E., Sellers L.A., Allen A., Cunliffe W.J., Morris E.R., and Ross-Murphy S.B. Properties of gastric and duodenal mucus: effect of proteolysis, disulfide reduction, bile, acid, ethanol, and hypertonicity on mucus gel structure. Gastroenterology 88 (1985) 269-280
15. Sellers L.A., Allen A., Morris E.R., and Ross-Murphy S.B. Mechanical characterization and properties of gastrointestinal mucus gel. Biorheology 24 (1987) 615-623
16. Ogston A., Preson B., and Wells J. On the transport of compact particles through solutions of chain polymers. Proc. R. Soc. Lond. 333 (1973) 297-316
17. Perrins W., McKenzie D., and McPhedran R. Transport properties of regular arrays of cylinders. Proc. R. Soc. Lond. 369 (1979) 207-225
18. Phillips R.J., Deen W.M., and Brady J.F. Hindered transport of spherical macromolecules in fibrous membranes and gels. AIChE J. 35 (1989) 1761-1769
19. Clague D., and Phillips R. Hindered diffusion of spherical macromolecules through dilute fibrous media. Phys. Fluids 8 (1996) 1720-1731
20. Johnson E.M., Berk D.A., Jain R.K., and Deen W.M. Hindered diffusion in agarose gels: test of effective medium model. Biophys. J. 70 (1996) 1017-1023
21. Deen W.M. Hindered transport of large molecules in liquid filled pores. AIChE J. 33 (1987)
22. Amsden B. Solute diffusion within hydrogels. Mechanisms and models. Macromolecules 31 (1998) 8382-8395
23. Amsden B. An obstruction-scaling model for diffusion in homogenous hydrogels. Macromolecules 32 (1999) 874-879
24. Renkin E.M. Filtration, diffusion, and molecular sieving through porous cellulose membranes. J. Gen. Physiol. 38 (1954) 225-243
25. Anderson J.L., and Quinn J.A. Restricted transport in small pores. A model for steric exclusion and hindered particle motion. Biophys. J. 14 (1974) 130-150
26. Florey H.W. The secretion and function of intestinal mucus. Gastroenterology 43 (1962) 326-329
27. Gruber P., Longer M.A., and Robinson J.R. Some biological issues in oral, controlled drug delivery. Adv. Drug Deliv. Rev. 1 (1987) 1-18
28. Lafitte G., Thuresson K., and Soderman O. Mixtures of mucin and oppositely charged surfactant aggregates with varying charge density. Phase behavior, association, and dynamics. Langmuir 21 (2005) 7097-7104
29. Anderson J.R., F., and Morales A. Particle diffusion as a function of concentration and ionic strength. J. Phys. Chem. 82 (1978)
30. Lai S.K., O'Hanlon D.E., Harrold S., Man S.T., Wang Y.Y., Cone R., and Hanes J. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 1482-1487
31. Olmsted S.S., Padgett J.L., Yudin A.I., Whaley K.J., Moench T.R., and Cone R.A. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys. J. 81 (2001) 1930-1937
32. Justin-Temu M., Damian F., Kinget R., and Van Den Mooter G. Intravaginal gels as drug delivery systems. J. Women's Health (Larchmt) 13 (2004) 834-844
33. Livingston E.H., and Engel E. Modeling of the gastric gel mucus layer: application to the measured pH gradient. J. Clin. Gastroenterol. 21 Suppl 1 (1995) S120-S124
34. Bhaskar K.R., Gong D.H., Bansil R., Pajevic S., Hamilton J.A., Turner B.S., and LaMont J.T. Profound increase in viscosity and aggregation of pig gastric mucin at low pH. Am. J. Physiol. 261 (1991) G827-832
35. Cao X., Bansil R., Bhaskar K.R., Turner B.S., LaMont J.T., Niu N., and Afdhal N.H. pH-dependent conformational change of gastric mucin leads to sol-gel transition. Biophys. J. 76 (1999) 1250-1258
36. Kaunitz J.D. Barrier function of gastric mucus. Keio J. Med. 48 (1999) 63-68
37. Schuhl J.F. Nasal mucociliary clearance in perennial rhinitis. J. Investig. Allergol. Clin. Immunol. 5 (1995) 333-336
38. Lehr C.M., Poelma F.G.J., Junginger H.E., and Tukker J.J. An estimate of turnover time of intestinal mucus gel layer in the rat in situ loop. Int. J. Pharm. 70 (1991) 235-240
39. W. M. Saltzman, in: (Ed.), Drug Delivery: Engineering Principles for Drug Therapy, Oxford University Press, New York, NY, 2001, 372.
40. Kosar T.F., and Phillips R.J. Measurement of protein diffusion in dextran solutions by holographic interferometry. AIChE J. 41 (1995) 701-711
41. Phillies G., Benedek G., and Mazer N. Diffusion in protein solutions at high concentrations: A study by quasielastic light scattering spectroscopy. J. Chem. Phys. 65 (1976) 1883-1892
42. Phillies G.D.J. Measurement of the (quasi)-self-diffusion coefficient of solutions of Brownian macroparticles. J. Chem. Phys. 81 (1984) 1487-1492
43. Eimer W.a.R.P. Rotational and translational diffusion of short rodlike molecules in solution: oligonucleotides. J. Chem. Phys. 94 (1991) 2324-2329
44. E. L. Cussler, in: (Ed.), Diffusion: Mass Transfer in Fluid Systems, Cambridge University Press, Cambridge, 1984, 525.
45. P. G. deGennes, in: (Ed.), Scaling Concepts in Polymer Physics, Cornell University Press, Ithaca, NY, 1979
46. Johansson L., and Löfroth J.E. Diffusion and interaction in gels and solutions. 4. Hard sphere Brownian dynamics simulations. J. Chem. Phys. 98 (1993) 7471-7480
47. Johansson L., Elvingson C., and Loefroth J.E. Diffusion and interaction in gels and solutions. 3. Theoretical results on the obstruction effect. Macromolecules 24 (1991) 6024-6029
48. Cukier R.I. Diffusion of Brownian spheres in semidilute polymer solutions. Macromolecules 17 (1984) 252-255
49. Peppas N.A., and Meadows D.L. Macromolecular structure and solute diffusion in membranes: an overview of recent theories. J. Membr. Sci. 16 (1983) 361-377
50. Pluen A., Netti P.A., Jain R.K., and Berk D.A. Diffusion of macromolecules in agarose gels: comparison of linear and globular configurations. Biophys. J. 77 (1999) 542-552
51. Gosnell D.L.a.B.H.Z. Measurement of diffusion coefficient of DNA in agarose gel. Macromolecules 26 (1993) 1304-1308
52. Shen H., Hu Y., and Saltzman W.M. DNA diffusion in mucus: effect of size, topology of DNAs, and transfection reagents. Biophys. J. 91 (2006) 639-644
53. Johansson L., Skantze U., and Loefroth J.E. Diffusion and interaction in gels and solutions. 2. Experimental results on the obstruction effect. Macromolecules 24 (1991) 6019-6023
54. Giddings J.C., Kucera E., Russel C.P., and Myers M.N. Statistical theory for the equilibrium distribution of rigid molecules in inert porous network. Exclusion chromatography. J. Phys. Chem. 72 (1968) 4397-4408
55. Pappenheimer J.R. Passage of molecules through capillary walls. Physiol. Rev. 33 (1953) 387-423
56. Pappenheimer J.R., Renkin E.M., and Borrero L.M. Filtration, diffusion and molecular sieving through peripheral capillary membranes; a contribution to the pore theory of capillary permeability. Am. J. Physiol. 167 (1951) 13-46
57. Brinkman H.C. A calculation of the viscous force exerted by a flowing fluid in a dense swarm of particles. Appl. Sci. Res. A. 1 (1947) 27-34
58. Phillies G. The hydrodynamic scaling model for polymer self-diffusion. J. Phys. Chem. 93 (1989) 5029-5039
59. Phillies G., Pirnat T., Kiss M., Teasdale N., Maclung D., Inglefield H., Malone C., Rau A., Yu L., and Rollings J. Probe diffusion in solutions of low molecular weight polyelectrolytes. Macromolecules 22 (1989)
60. Brady J. Hindered Diffusion, American Institute of Chemical Engineers, Annual Meeting (1994) 320
61. Tsai D.S., and Strieder W. Effective conductivities of random fiber beds. Chem. Eng. Commun. 40 (1986) 207-218
62. S. F. Sun, in: (Ed.), Physical Chemistry of Macromolecules: Basic Principles and Issues, John Wiley & Sons, Inc., Hoboken, New Jersey, 2004.
63. Murayama M., Okada M., Fukutomi T., and Nose T. Radius of gyration and hydrodynamic radius of branched polystyrenes in cyclohexane and toluene measured by static and dynamic light scattering. Makromol. Chem. 188 (1987) 829-843
64. Sanders N.N., De Smedt S.C., and Demeester J. The physical properties of biogels and their permeability for macromolecular drugs and colloidal drug carriers. J. Pharm. Sci. 89 (2000) 835-849
65. Allen J.D., Martin G.P., Marriott C., Hassan I., and Williamson I. Drug transport across a novel mucin secreting cell model: comparison with the Caco-2 cell system. J. Pharm. Pharmacol. 43 (1991) 63P
66. Behrens I., Stenberg P., Artursson P., and Kissel T. Transport of lipophilic drug molecules in a new mucus-secreting cell culture model based on HT29-MTX cells. Pharm. Res. 18 (2001) 1138-1145
67. Phillips T.E., Huet C., Bilbo P.R., Podolsky D.K., Louvard D., and Neutra M.R. Human intestinal goblet cells in monolayer culture: characterization of a mucus-secreting subclone derived from the HT29 colon adenocarcinoma cell line. Gastroenterology 94 (1988) 1390-1403
68. Tabuchi Y., Ohta S., Arai Y., Kawahara M., Ishibashi K., Sugiyama N., Horiuchi T., Furusawa M., Obinata M., Fuse H., Takeguchi N., and Asano S. Establishment and characterization of a colonic epithelial cell line MCE301 from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene. Cell. Struct. Funct. 25 (2000) 297-307
69. Wikman A., Karlsson J., Carlstedt I., and Artursson P. A drug absorption model based on the mucus layer producing human intestinal goblet cell line HT29-H. Pharm. Res. 10 (1993) 843-852
70. Ootani A., Toda S., Fujimoto K., and Sugihara H. Foveolar differentiation of mouse gastric mucosa in vitro. Am. J. Pathol. 162 (2003) 1905-1912
71. Karlsson J., Wikman A., and Artursson P. The mucus layer as a barrier to drug absorption in monolayers of human intestinal epithelial HT29-H goblet cells. Int. J. Pharmaceutics 99 (1993) 209-218
72. Broughton-Head V.J., Smith J.R., Shur J., and Shute J.K. Actin limits enhancement of nanoparticle diffusion through cystic fibrosis sputum by mucolytics. Pulm. Pharmacol. Ther. (2006)
73. Dawson M., Wirtz D., and Hanes J. Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. J. Biol. Chem. 278 (2003) 50393-50401
74. Westrin B.A., Axelsson A., and Zacchi G. Diffusion measurement in gels. J. Control. Release 30 (1994) 198-199
75. Lukie B.E., Westergaard H., and Dietschy J.M. Validation of a chamber that allows measurement of both tissue uptake rates and unstirred layer thicknesses in the intestine under conditions of controlled stirring. Gastroenterology 67 (1974) 652-661
76. Desai M.A., and Vadgama P. Estimation of effective diffusion coefficients of model solutes through gastric mucus: assessment of a diffusion chamber technique based on spectrophotometric analysis. Analyst 116 (1991) 1113-1116
77. Norris D.A., and Sinko P.J. Effect of size, surface charge, and hydrophobicity on the translocation of polystyrene microspheres through gastrointestinal mucin. J. Appl. Polym. Sci. 63 (1997) 1481-1492
78. Lin C.C., and Segel L.A. Mathematics applied to deterministic problems in the natural sciences. In: Golub G.H. (Ed). Classics in Applied Mathematics (1995), Macmillan Publishing Co., New York, NY 609
79. Radomsky M.L., Whaley K.J., Cone R.A., and Saltzman W.M. Macromolecules released from polymers: diffusion into unstirred fluids. Biomaterials 11 (1990) 619-624
80. Johnson E.M., Berk D.A., Jain R.K., and Deen W.M. Diffusion and partitioning of proteins in charged agarose gels. Biophys. J. 68 (1995) 1561-1568
81. Berk D.A., Yuan F., Leunig M., and Jain R.K. Fluorescence photobleaching with spatial Fourier analysis: measurement of diffusion in light-scattering media. Biophys. J. 65 (1993) 2428-2436
82. Liedl T., Keller S., Simmel F.C., Radler J.O., and Parak W.J. Fluorescent nanocrystals as colloidal probes in complex fluids measured by fluorescence correlation spectroscopy. Small 1 (2005) 997-1003
83. Henry B.T., Adler J., Hibberd S., Cheema M.S., Davis S.S., and Rogers T.G. Epi-fluorescence microscopy and image analysis used to measure diffusion coefficients in gel systems. J. Pharm. Pharmacol. 44 (1992) 543-549
84. Amsden B., and Turner N. Diffusion characteristics of calcium alginate gels. Biotechnol. Bioeng. 65 (1999) 605-610
85. Park I., Johnson C., and Gabriel D. Probe diffusion in polyacrylamide gels as observed by means of holographic relaxation methods: search for a universal equation. Macromolecules 23 (1990) 1548-1553
86. Fair B., Chao D., and Jamieson A. Mutual translational diffusion coefficients in bovine serum albumin solutions measured by quasielastic laser light scattering. J. Colloid Interface Science. 66 (1978) 324-330
87. Soda K., and Wada A. Dynamic light-scattering studies on thermal motion of native DNAs in solution. Biophys. Chem. 20 (1984) 185-200
88. Gibbs S.J., Lightfoot E.N., and Root T.W. Protein diffusion in porous gel filtration chromatographic media studied by pulsed field gradient NMR-spectroscopy. J. Phys. Chem. 96 (1992) 7458-7462
89. Lafitte G., Soderman O., Thuresson K., and Davies J. PFG-NMR diffusometry: a tool for investigating the structure and dynamics of noncommercial purified pig gastric mucin in a wide range of concentrations. Biopolymers 86 (2007) 165-175
90. Lafitte G., Thuresson K., and Soderman O. Diffusion of nutrients molecules and model drug carriers through mucin layer investigated by magnetic resonance imaging with chemical shift resolution. J. Pharm. Sci. 96 (2007) 258-263
91. Conrath G.e.a. In situ determination of the diffusion coefficient of a solute in a gel system using a radiotracer. J. Control. Release 9 (1989) 159-168
92. Desai M.A., Mutlu M., and Vadgama P. A study of macromolecular diffusion through native porcine mucus. Experientia 48 (1992) 22-26
93. Larhed A.W., Artursson P., Grasjo J., and Bjork E. Diffusion of drugs in native and purified gastrointestinal mucus. J. Pharm. Sci. 86 (1997) 660-665
94. Osth K., Strindelius L., Larhed A., Ahlander A., Roomans G.M., Sjoholm I., and Bjork E. Uptake of ovalbumin-conjugated starch microparticles by pig respiratory nasal mucosa in vitro. J. Drug Target 11 (2003) 75-82
95. Szentkuti L. Light microscopical observations on luminally administered dyes, dextrans, nanospheres and microspheres in the pre-epithelial mucus gel layer of the rat distal colon. J. Control. Release 46 (1997) 233-242
96. Williams R.M., Piston D.W., and Webb W.W. Two-photon molecular excitation provides intrinsic 3-dimensional resolution for laser-based microscopy and microphotochemistry. Faseb J. 8 (1994) 804-813
97. Xu C., Zipfel W., Shear J.B., Williams R.M., and Webb W.W. Multiphoton fluorescence excitation: New spectral windows for biological nonlinear microscopy. Proc. Natl. Acad. Sci. U. S. A. 93 (1996) 10763-10768
98. Meyvis T.K., De Smedt S.C., Van Oostveldt P., and Demeester J. Fluorescence recovery after photobleaching: a versatile tool for mobility and interaction measurements in pharmaceutical research. Pharm. Res. 16 (1999) 1153-1162
99. Wolf D.E. Designing, building, and using a fluorescence recovery after photobleaching instrument. Fluorescence. Microscopy of Living Cells in Culture Part B. (1989) 271-306
100. Bohrer M.P., Patterson G.D., and Carroll P.J. Hindered diffusion of dextran and Ficoll in microporous membranes. Macromolecules 17 (1984) 1170-1173
101. Kosto K.B., and Deen W.M. Hindered convection of macromolecules in hydrogels. Biophys. J. 88 (2005) 277-286
102. Kosto K.B., Panuganti S., and Deen W.M. Equilibrium partitioning of Ficoll in composite hydrogels. J. Colloid Interface Sci. 277 (2004) 404-409
103. Willits R.K., and Saltzman W.M. Synthetic polymers alter the structure of cervical mucus. Biomaterials 22 (2001) 445-452
104. Willits R.K., and Saltzman W.M. The effect of synthetic polymers on the migration of monocytes through human cervical mucus. Biomaterials 25 (2004) 4563-4571
105. Pontier C., Pachot J., Botham R., Lenfant B., and Arnaud P. HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption: role of the mucus layer. J. Pharm. Sci. 90 (2001) 1608-1619
106. Choe M.M., Tomei A.A., and Swartz M.A. Physiological 3D tissue model of the airway wall and mucosa. Nat. Protoc. 1 (2006) 357-362
107. Choe M.M., Sporn P.H., and Swartz M.A. An in vitro airway wall model of remodeling. Am. J. Physiol., Lung Cell Mol. Physiol. 285 (2003) L427-433
108. Lee W.I., Verdugo P., Blandau R.J., and Gaddum-Rosse P. Molecular arrangement of cervical mucus: a reevaluation based on laser light-scattering spectroscopy. Gynecology. Investigation 8 (1977) 154-166
109. Sheehan J.K., Oates K., and Carlstedt I. Electron microscopy of cervical, gastric and bronchial mucus glycoproteins. Biochem. J. 239 (1986) 147-153
110. Neutra M.R., and Forstner J.F. Gastrointestinal mucus: synthesis, secretion, and function. In: Johnson L.R. (Ed). Physiology of the Gastrointestinal Tract (1987), Raven Press, New York, NY 975-1009
111. Sellers L.A., Allen A., Morris E.R., and Ross-Murphy S.B. The rheology of pig small intestinal and colonic mucus: weakening of gel structure by non-mucin components. Biochim. Biophys. Acta 1115 (1991) 174-179
112. Peppas N., Hansen P., and Buri P. A theory of molecular diffusion in the intestinal mucus. Int. J. Pharm. 20 (1984) 107-118
113. Bhat P.G., Flanagan D.R., and Donovan M.D. Drug diffusion through cystic fibrotic mucus: steady-state permeation, rheologic properties, and glycoprotein morphology. J. Pharm. Sci. 85 (1996) 624-630
114. Dykstra K.H., Hsiao J.K., Morrison P.F., Bungay P.M., Mefford I.N., Scully M.M., and Dedrick R.L. Quantitative examination of tissue concentration profiles associated with microdialysis. J. Neurochem. 58 (1992) 931-940
115. Gustafsson N.O., Westrin B., Axelsson A., and Zacchi G. Measurement of diffusion coefficients in gels using holographic laser interferometry. Biotechnol. Prog. 9 (1993) 436-441
116. Tolo K., Brandtzaeg P., and Jonsen J. Mucosal penetration of antigen in the presence or absence of serum-derived antibody. Immunology 33 (1977) 733-743