Biological hydrogels as selective diffusion barriers

Lieleg, Oliver; Ribbeck, Katharina

doi:10.1016/j.tcb.2011.06.002

Cited by 387Hydrogels: synthesis, properties, applicationsChemical and Physical StudiesSupramolecular Self-Assembly in Materials

Biological hydrogels as selective diffusion barriers

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Lieleg, Oliver, Ribbeck, Katharina·2011·Trends in Cell Biology

DOI 10.1016/j.tcb.2011.06.002PMC PMC3164742

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Abstract

The controlled exchange of molecules between organelles, cells, or organisms and their environment is crucial for life. Biological gels such as mucus, the extracellular matrix (ECM), and the biopolymer barrier within the nuclear pore are well suited to achieve such a selective exchange, allowing passage of particular molecules while rejecting many others. Although hydrogel-based filters are integral parts of biology, clear concepts of how their barrier function is controlled at a microscopic level are still missing. We summarize here our current understanding of how selective filtering is established by different biopolymer-based hydrogels. We ask if the modulation of microscopic particle transport in biological hydrogels is based on a generic filtering principle which employs biochemical/biophysical interactions with the filtered molecules rather than size-exclusion effects.

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Background
Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier
Lee, D., & Minko, T. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122049 · Cited by 219 · see citing works
“These interactions include electrostatic forces, hydrophobic, and Van der Waal’s bonds [67].”
Background
Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues
Yu, M., Wang, J., Yang, Y., Zhu, C., Su, Q., Guo, S., Sun, J., Gan, Y., Shi, X., & Gao, H. (2016) · Nano Letters · doi:10.1021/acs.nanolett.6b03515 · Cited by 204 · see citing works
The Influence of Nanoparticle Properties on Oral Bioavailability of Drugs
Wang, Y., Pi, C., Feng, X., Hou, Y., Zhao, L., & Wei, Y. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s257269 · Cited by 201 · see citing works
Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus
Kirch, J., Schneider, A., Abou, B., Hopf, A., Schaefer, U. F., Schneider, M., Schall, C., Wagner, C., & Lehr, C. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214066109 · Cited by 190 · see citing works
“Current studies in this field either focus on pore size as limiting factor (10, 11) or suggest the more complex interaction filtering of mucus rather than size exclusion effects (6).”
Background
The Mucus Barrier to Inhaled Gene Therapy
Duncan, G. A., Jung, J., Hanes, J. S., & Suk, J. S. (2016) · Molecular Therapy · doi:10.1038/mt.2016.182 · Cited by 189 · see citing works
Combinatorial development of nebulized mRNA delivery formulations for the lungs
Jiang, A. Y., Witten, J. J., Raji, I. O., Eweje, F., MacIsaac, C., Meng, S., Oladimeji, F. A., Hu, Y., Manan, R. S., Langer, R., et al. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01548-3 · Cited by 191 · see citing works
“Second, transfecting the bronchial epithelium requires penetration of a mucus layer that is a steric and chemical barrier to diffusion 51–54 .”
Mechanics of 3D Cell–Hydrogel Interactions: Experiments, Models, and Mechanisms
Vernerey, F. J., Sridhar, S. L., Muralidharan, A., & Bryant, S. J. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00046 · Cited by 183 · see citing works
Non-Gaussian, non-ergodic, and non-Fickian diffusion of tracers in mucin hydrogels
Cherstvy, A. G., Thapa, S., Wagner, C. E., & Metzler, R. (2019) · Soft Matter · doi:10.1039/c8sm02096e · Cited by 171 · see citing works
Selective permeability of mucus barriers
Witten, J. J., Samad, T. S., & Ribbeck, K. (2018) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2018.03.010 · Cited by 171 · see citing works
“For particles that are larger than the mesh size, mucus presents a geometrically constraining filter and hinders their passage regardless of surface chemistry (Figure 1b) [12].”
Spatial Configuration and Composition of Charge Modulates Transport into a Mucin Hydrogel Barrier
Li, L. D., Crouzier, T., Sarkar, A., Dunphy, L. J., Han, J., & Ribbeck, K. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2013.07.050 · Cited by 159 · see citing works
Abundance and Distribution of Enteric Bacteria and Viruses in Coastal and Estuarine Sediments—a Review
Hassard, F., Gwyther, C. L., Farkas, K., Andrews, A., Jones, V., Cox, B. A., Brett, H., Jones, D. L., McDonald, J. E., & Malham, S. K. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01692 · Cited by 155 · see citing works
“These environments tend to be deficient in a growth limiting electron acceptor or nutrient and therefore facilitate a greater proportion of VBNC bacteria than expected in free floating systems (Bryers, 2000; Amel et al., 2008; Lieleg and Ribbeck, 2011).”
Background
The in vivo fate of polymeric micelles
Cai, Y., Qi, J., Lu, Y., He, H., & Wu, W. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114463 · Cited by 154 · see citing works
The particle in the spider's web: transport through biological hydrogels
Witten, J. J., & Ribbeck, K. (2017) · Nanoscale · doi:10.1039/c6nr09736g · Cited by 148 · see citing works
Biopolymer‐Based Coatings: Promising Strategies to Improve the Biocompatibility and Functionality of Materials Used in Biomedical Engineering
Song, J., Winkeljann, B., & Lieleg, O. (2020) · Advanced Materials Interfaces · doi:10.1002/admi.202000850 · Cited by 155 · see citing works
Bayesian analysis of single-particle tracking data using the nested-sampling algorithm: maximum-likelihood model selection applied to stochastic-diffusivity data
Thapa, S., Lomholt, M. A., Krog, J., Cherstvy, A. G., & Metzler, R. (2018) · Physical Chemistry Chemical Physics · doi:10.1039/c8cp04043e · Cited by 142 · see citing works
Size-Limited Penetration of Nanoparticles into Porcine Respiratory Mucus after Aerosol Deposition
Murgia, X., Pawelzyk, P., Schaefer, U. F., Wagner, C., Willenbacher, N., & Lehr, C.-M. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.6b00164 · Cited by 144 · see citing works
Mucin gel assembly is controlled by a collective action of non-mucin proteins, disulfide bridges, Ca2+-mediated links, and hydrogen bonding
Meldrum, O. W., Yakubov, G. E., Bonilla, M. R., Deshmukh, O. S., McGuckin, M. A., & Gidley, M. J. (2018) · Scientific Reports · doi:10.1038/s41598-018-24223-3 · Cited by 139 · see citing works
Diffusion-Limited Processes in Hydrogels with Chosen Applications from Drug Delivery to Electronic Components
Lavrentev, F. V., Shilovskikh, V. V., Alabusheva, V. S., Yurova, V. Y., Nikitina, A. A., Ulasevich, S. A., & Скорб, Е. В. (2023) · Molecules · doi:10.3390/molecules28155931 · Cited by 138 · see citing works
“More rapid diffusion occurs when the mesh size is larger than the encapsulated drug (rmesh/rdrug > 1) unless specific bonding forms between the molecule and the polymer chain [97].”
Background
Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions
Nakamura, H., Lee, A. A., Afshar, A. S., Watanabe, S., Rho, E., Razavi, S., Suarez, A., Lin, Y., Tanigawa, M., Huang, B., et al. (2017) · Nature Materials · doi:10.1038/nmat5006 · Cited by 131 · see citing works
“Molecular Aggregates as Sieves and their Effective Pore Sizes Molecular aggregates, such as the ones produced in this work, are known to form a selective three-dimensional gel-like sieve that interferes only slightly with the motion of small molecules but appreciably slows down the motion of large molecules and blocks…”
Permeability mapping of gelatin methacryloyl hydrogels
Miri, A. K., Hosseinabadi, H. G., Çeçen, B., Hassan, S., & Zhang, Y. S. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.07.006 · Cited by 133 · see citing works
Particle Targeting in Complex Biological Media
Dai, Q., Bertleff‐Zieschang, N., Braunger, J. A., Björnmalm, M., Cortez‐Jugo, C., & Caruso, F. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700575 · Cited by 130 · see citing works
Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors
Alhajlan, M. M. A., Alhariri, M., & Omri, A. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00235-13 · Cited by 125 · see citing works
“Furthermore, the extracellular polymeric matrix delays the diffusion of some antibiotics into the community (27, 32), and thus, bacteria might be exposed to a drug concentration below the MIC, leading to increased mutation and resistance of the bacteria (33).”
Background
Pore-size dependence and slow relaxation of hydrogel friction on smooth surfaces
Cuccia, N., Pothineni, S., Wu, B., Harper, J. M., & Burton, J. C. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922364117 · Cited by 113 · see citing works
Diffusion Regulation in the Vitreous Humor
Käsdorf, B. T., Arends, F., & Lieleg, O. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2015.10.002 · Cited by 113 · see citing works
“A similar charge-dependent suppression of particle diffusion has also been observed in other biological hydrogel systems (23–27), which suggests that this might be a more generic filtering mechanism in biology (28).”
Background
Engineering nanoparticles to overcome the mucus barrier for drug delivery: Design, evaluation and state-of-the-art
Liu, C., Jiang, X., Gan, Y., & Yu, M. (2021) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2021.100110 · Cited by 106 · see citing works
Acute Exposure to Commonly Ingested Emulsifiers Alters Intestinal Mucus Structure and Transport Properties
Lock, J. Y., Carlson, T. L., Wang, C.-M., Chen, A., & Carrier, R. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-27957-2 · Cited by 105 · see citing works
How do polymeric micelles cross epithelial barriers?
Pepić, I., Lovrić, J., & Filipović-Grčić, J. (2013) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.04.012 · Cited by 102 · see citing works
Novel drug delivery systems for inflammatory bowel disease
Yasmin, F., Najeeb, H., Shaikh, S., Hasanain, M., Naeem, U., Moeed, A., Koritala, T., Hasan, S., & Surani, S. (2022) · World Journal of Gastroenterology · doi:10.3748/wjg.v28.i18.1922 · Cited by 102 · see citing works
Effect of Ion–Ion Correlations on Polyelectrolyte Gel Collapse and Reentrant Swelling
Sing, C. E., Zwanikken, J. W., & de la Cruz, M. O. (2013) · Macromolecules · doi:10.1021/ma400372p · Cited by 100 · see citing works
A Comprehensive Review of Radiation-Induced Hydrogels: Synthesis, Properties, and Multidimensional Applications
Ahmed, M. S., Islam, M., Hasan, M. K., & Nam, K. (2024) · Gels · doi:10.3390/gels10060381 · Cited by 98 · see citing works
“These characteristics evoke a semblance to biological materials like mucus or the extracellular matrix enveloping cells, tissues, organs, or entire organisms [23,24].”
Background
Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies
Abdulkarim, M., Sharma, P. K., & Gumbleton, M. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.04.001 · Cited by 95 · see citing works
“Physically, intestinal mucus can be described as a semipermeable membrane from which only particles as small as nutrients and drug molecules can permeate [36].”
Background
Mucus-Inspired Dynamic Hydrogels: Synthesis and Future Perspectives
Bej, R., & Haag, R. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.1c13547 · Cited by 95 · see citing works
Optimization by design of etoposide loaded solid lipid nanoparticles for ocular delivery: Characterization, pharmacokinetic and deposition study
Ahmad, I. N., Pandit, J., Sultana, Y., Mishra, A. K., Hazari, P. P., & Aqil, M. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.03.060 · Cited by 92 · see citing works
Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy
Shamsi, M., Sedaghatkish, A., Dejam, M., Saghafian, M., Mohammadi, M., & Sanati‐Nezhad, A. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1455764 · Cited by 89 · see citing works
“The cutoff size of the ECM and particles as well as the particle–ECM chemical interactions are the main determinants of the extracellular particle diffusion (Lieleg & Ribbeck, 2011; Witten & Ribbeck, 2017).”
Background
Membrane Proteins Significantly Restrict Exosome Mobility
Skliar, M., Chernyshev, V. S., Belnap, D. M., Sergey, G. V., Al-Hakami, S. M., Bernard, P. S., Stijleman, I. J., & Rachamadugu, R. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.107 · Cited by 89 · see citing works
Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery
Duffy, C. V., David, L., & Crouzier, T. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.03.024 · Cited by 88 · see citing works
Chain-Length- and Saturation-Tuned Mechanics of Fluid Nanovesicles Direct Tumor Delivery
Dai, Z., Yu, M., Yi, X., Wu, Z., Tian, F., Miao, Y., Song, W., He, S., Ahmad, E., Guo, S., et al. (2019) · ACS Nano · doi:10.1021/acsnano.9b01181 · Cited by 87 · see citing works
Superhydrophobic Diffusion Barriers for Hydrogels via Confined Interfacial Modification
Yao, X., Chen, L., Ju, J., Li, C., Tian, Y. F., Jiang, L., & Liu, M. (2016) · Advanced Materials · doi:10.1002/adma.201601568 · Cited by 86 · see citing works
Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics
Bourganis, V., Karamanidou, T., Kammona, O., & Kiparissides, C. A. (2016) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2016.11.005 · Cited by 84 · see citing works
“It has been experimentally verified that size exclusion could be an appropriate framework for the description of mucus permeation, as an increase in particle diameter correlates with a decrease in particle mobility [42,43].”
Background
Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery system intended for the treatment of bacterial infections in cystic fibrosis
Torge, A., Wagner, S., Chaves, P., de Oliveira, E. G., Guterres, S. S., Pohlmann, A. R., Titz, A., Schneider, M., & Beck, R. C. R. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.05.013 · Cited by 84 · see citing works
Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions
Popov, A. (2020) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2020.0022 · Cited by 83 · see citing works
“These side chains contain 2–22 sugar units and can be can linear or moderately branched, conferring mucins with a brush-like structure.(22,30) Due to the high prevalence of sialic acid (pKa 2.”
Background
Cervical Mucus Properties Stratify Risk for Preterm Birth
Critchfield, A. S., Yao, G., Jaishankar, A., Friedlander, R. S., Lieleg, O., Doyle, P. S., McKinley, G. H., House, M. D., & Ribbeck, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069528 · Cited by 83 · see citing works
“However, the barrier function of the mucus hydrogel depends not only on molecular mediators but also on the physical and mucoadhesive properties of the mucin fibers [31].”
Background
Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
Radwan, S. E.-S., El-Kamel, A. H., Zaki, E. I., Burgalassi, S., Zucchetti, E., & El‐Moslemany, R. M. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s316564 · Cited by 81 · see citing works
The Vitreous Humor As a Barrier to Nanoparticle Distribution
Mains, J., & WILSON, C. G. (2012) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2012.0138 · Cited by 81 · see citing works
“The nature of the vitreous humor plays a key role in charge-related particle distribution effects due to the anionic medium created by its structure.(45) Due to the overall anionic charge of the vitreous, it is anticipated that anionic particles will distribute through the vitreous without any major restriction, where…”
Biopolymeric Mucin and Synthetic Polymer Analogs: Their Structure, Function and Role in Biomedical Applications
Authimoolam, S. P., & Dziubla, T. D. (2016) · Polymers · doi:10.3390/polym8030071 · Cited by 80 · see citing works
“Figure was adapted from References [105,106].”
Recent Development of Drug Delivery Systems through Microfluidics: From Synthesis to Evaluation
Ma, Z., Li, B.-C., Peng, J., & Gao, D. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020434 · Cited by 59 · see citing works
“As shown in Figure 4B [108], the mucin network can form a size exclusion filter for larger compounds [87].”
Background
Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation
Boegh, M., García-Díaz, M., Müllertz, A., & Nielsen, H. M. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.01.014 · Cited by 78 · see citing works
“In addition to this steric barrier, mucus also comprises an important interactive component as the formation of multiple non-covalent bonds may immobilize a drug or particle in the mucus network [2,5,6].”
Background
Air-Liquid interface cultures to model drug delivery through the mucociliary epithelial barrier
Lee, R. E., Reidel, B., Nelson, M. R., Macdonald, J. K., Kesimer, M., & Randell, S. H. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114866 · Cited by 71 · see citing works
Microfluidics as tool to prepare size-tunable PLGA nanoparticles with high curcumin encapsulation for efficient mucus penetration
Lababidi, N., Sigal, V., Koenneke, A., Schwarzkopf, K. R. G., Manz, A., & Schneider, M. (2019) · Beilstein Journal of Nanotechnology · doi:10.3762/bjnano.10.220 · Cited by 77 · see citing works
Interactions of Microbicide Nanoparticles with a Simulated Vaginal Fluid
das Neves, J., Rocha, C. M. R., Gonçalves, M. P., Carrier, R. L., Amiji, M. M., Bahia, M. F., & Sarmento, B. F. C. C. (2012) · Molecular Pharmaceutics · doi:10.1021/mp300408m · Cited by 76 · see citing works
From Nature‐Sourced Polysaccharide Particles to Advanced Functional Materials
Ma, Y., Morozova, S. M., & Kumacheva, E. (2024) · Advanced Materials · doi:10.1002/adma.202312707 · Cited by 72 · see citing works
Particle Transport through Hydrogels Is Charge Asymmetric
Zhang, X., Hansing, J., Netz, R. R., & DeRouchey, J. E. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2014.12.009 · Cited by 72 · see citing works
“These interactions seem to be of an electrostatic nature, since the mobility is highly dependent on the particle surface charge (4,9,10,14,15,29,30) and the salt concentration (8–10,31,32).”
Background
Mechanistic action of weak acid drugs on biofilms
Kundukad, B., Schussman, M., Yang, K., Seviour, T. W., Yang, L., Rice, S. A., Kjelleberg, S. J., & Doyle, P. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-05178-3 · Cited by 71 · see citing works
Implications of designing clarithromycin loaded solid lipid nanoparticles on their pharmacokinetics, antibacterial activity and safety
Sharma, M., Gupta, N., & Gupta, S. (2016) · RSC Advances · doi:10.1039/c6ra12841f · Cited by 71 · see citing works
Dynamic Manipulation of Hydrogels to Control Cell Behavior: A Review
Vats, K., & Benoit, D. S. W. (2013) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0716 · Cited by 70 · see citing works
“, crosslinking density).(33) Also, just like the native ECM, hydogels possess both viscous and elastic behaviors.”
Background
Enhanced Heterogeneous Diffusion of Nanoparticles in Semiflexible Networks
Xu, Z., Dai, X., Bu, X., Ye, Y., Zhang, X., Man, X., Zhang, X., Doi, M., & Yan, L. (2021) · ACS Nano · doi:10.1021/acsnano.0c08877 · Cited by 69 · see citing works
Purely Polysaccharide-Based Biofilm Matrix Provides Size-Selective Diffusion Barriers for Nanoparticles and Bacteriophages
Dunsing, V., Irmscher, T., Barbirz, S., & Chiantia, S. (2019) · Biomacromolecules · doi:10.1021/acs.biomac.9b00938 · Cited by 68 · see citing works
Impermeable Robust Hydrogels via Hybrid Lamination
Parada, G. A., Yuk, H., Liu, X., Hsieh, A. J., & Zhao, X. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700520 · Cited by 68 · see citing works
Enhanced diffusion by binding to the crosslinks of a polymer gel
Goodrich, C. P., Brenner, M. P., & Ribbeck, K. (2018) · Nature Communications · doi:10.1038/s41467-018-06851-5 · Cited by 68 · see citing works
Bilayer Hydrogels for Wound Dressing and Tissue Engineering
Luneva, O., Olekhnovich, R. O., & Uspenskaya, M. V. (2022) · Polymers · doi:10.3390/polym14153135 · Cited by 66 · see citing works
The use of HA oligosaccharide-loaded nanoparticles to breach the endogenous hyaluronan glycocalyx for breast cancer therapy
Yang, C., Liu, Y., He, Y., Du, Y., Wang, W., Shi, X., & Gao, F. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.05.036 · Cited by 66 · see citing works
pH-Mediated Mucus Penetration of Zwitterionic Polydopamine-Modified Silica Nanoparticles
Ma, Y., Guo, Y., Liu, S., Hu, Y., Yang, C., Cheng, G., Xue, C., Zuo, Y. Y., & Sun, B. (2023) · Nano Letters · doi:10.1021/acs.nanolett.3c02128 · Cited by 63 · see citing works
Technological strategies to estimate and control diffusive passage times through the mucus barrier in mucosal drug delivery
Newby, J., Seim, I., Lysy, M., Ling, Y., Huckaby, J. T., Lai, S. K., & Forest, M. G. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.12.002 · Cited by 63 · see citing works
“[32] Oliver Lieleg and Katharina Ribbeck, “Biological hydrogels as selective diffusion barriers,” Trends in cell biology 21, 543–551 (2011).”
Peptides as surface coatings of nanoparticles that penetrate human cystic fibrosis sputum and uniformly distribute in vivo following pulmonary delivery
Leal, J., Peng, X., Liu, X., Arasappan, D., Wylie, D., Schwartz, S. H., Fullmer, J. J., McWilliams, B., Smyth, H. D. C., & Ghosh, D. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.03.032 · Cited by 62 · see citing works
“The mucus layer acts as a transport barrier and can greatly hinder the diffusion of drugs, particles, and other molecules via size filtering, mucociliary clearance, and intermolecular interactions, including electrostatic, hydrophobic, and/or other specific binding interactions [2].”
Background
Hyaluronan content governs tissue stiffness in pancreatic islet inflammation
Nagy, N., de la Zerda, A., Kaber, G., Johnson, P. Y., Hu, K. H., Kratochvil, M. J., Yadava, K., Zhao, W., Cui, Y., Navarro, G., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000148 · Cited by 60 · see citing works
Advances in regulating physicochemical properties of mesoporous silica nanocarriers to overcome biological barriers
Wang, Y., Gou, K., Guo, X., Ke, J., Li, S., & Li, H. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.01.005 · Cited by 61 · see citing works
Colloidal multiscale porous adhesive (bio)inks facilitate scaffold integration
Mostafavi, A., Samandari, M., Karvar, M., Ghovvati, M., Endo, Y., Sinha, I., Annabi, N., & Tamayol, A. (2021) · Applied Physics Reviews · doi:10.1063/5.0062823 · Cited by 61 · see citing works
“19 In addition, poor cell inﬁltration and spreading within these hydrogels further limit early vascularization and innervation, thus impairing the viability and functionality of encapsulated cells.”
Polymer Structure Dependent Hierarchy in PolyMOC Gels
Zhukhovitskiy, A. V., Zhao, J. X., Zhong, M., Keeler, E. G., Alt, E. A., Teichen, P. E., Griffin, R. G., Hore, M. J. A., Willard, A. P., & Johnson, J. A. (2016) · Macromolecules · doi:10.1021/acs.macromol.6b01607 · Cited by 61 · see citing works
How the Shape and Chemistry of Molecular Penetrants Control Responsive Hydrogel Permeability
Kanduč, M., Kim, W. K., Roa, R., & Dzubiella, J. (2020) · ACS Nano · doi:10.1021/acsnano.0c06319 · Cited by 61 · see citing works
“46,47 A simple and popular model that treats the steric hindrance e ﬀ ect is the Mackie − Meares model, 48 which we will use in our approach: i k jjjjj y { zzzzz Here, the di ﬀ usion coe ﬃ cient in bulk water, D w , is attenuated by a steric factor, in which the e ﬀ ective polymer volume fraction…”
Modulation of Gastrointestinal Mucus Properties with Ionic Liquids for Drug Delivery
Peng, K., Gao, Y., Angsantikul, P., Labarbiera, A., Goetz, M. J., Curreri, A. M., Rodrigues, D., Tanner, E. E. L., & Mitragotri, S. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202002192 · Cited by 58 · see citing works
Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix
Tomasetti, L., & Breunig, M. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700739 · Cited by 58 · see citing works
Lipid-based mucus penetrating nanoparticles and their biophysical interactions with pulmonary mucus layer
Alp, G., & Aydoğan, N. (2020) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2020.01.017 · Cited by 56 · see citing works
Physiological properties, composition and structural profiling of porcine gastrointestinal mucus
Barmpatsalou, V., Dubbelboer, I. R., Rodler, A., Jacobson, M., Karlsson, Ε., Pedersen, B. L., & Bergström, C. A. S. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.10.008 · Cited by 54 · see citing works
“Additionally, the barrier function of the mucus — that keeps the bacteria and other pathogens at a safe distance from the GIT epithelium [7] — may pose steric limitations to the diffusing drugs [8].”
Background
Polymer Conformations in Ionic Microgels in the Presence of Salt: Theoretical and Mesoscale Simulation Results
Kobayashi, H., Halver, R., Sutmann, G., & Winkler, R. G. (2017) · Polymers · doi:10.3390/polym9010015 · Cited by 54 · see citing works
“, the extra-cellular matrix or mucus [10,11].”
Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles
Schulz, R., Yamamoto, K., Klossek, A., Flesch, R., Hönzke, S., Rancan, F., Vogt, A., Blume‐Peytavi, U., Hedtrich, S., Schäfer‐Korting, M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620636114 · Cited by 54 · see citing works
Modularized Field-Effect Transistor Biosensors
Dai, X., Vo, R., Hsu, L. H. H., Deng, P. J., Zhang, Y., & Jiang, X. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b02939 · Cited by 54 · see citing works
Dependence of structure of polymer side chain on water structure in hydrogels
Sekine, Y., Takagi, H., Sudo, S., Kajiwara, Y., Fukazawa, H., & Ikeda‐Fukazawa, T. (2014) · Polymer · doi:10.1016/j.polymer.2014.10.011 · Cited by 53 · see citing works
Creating 3D Angiogenic Growth Factor Gradients in Fibrous Constructs to Guide Fast Angiogenesis
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Authors: Lieleg, O., & Ribbeck, K.
Affiliations: Massachusetts Institute of Technology (US)
Corresponding author: Ribbeck, Katharina
ORCID: Lieleg, Oliver
Ribbeck, Katharina
Venue: Trends in Cell Biology
Publisher: Elsevier BV
Published: 2011-09
Volume: 21
Issue: 9
Pages: 543-551
ISSN: 0962-8924 (ISSN-L)
DOI: 10.1016/j.tcb.2011.06.002
PMC: PMC3164742
OpenAlex: W2039548511
Cited by: 387
References: 79
Citations by year: 2026: 25 · 2025: 32 · 2024: 29 · 2023: 33 · 2022: 28 · 2021: 31 · 2020: 33 · 2019: 32 · 2018: 26 · 2017: 31 · 2016: 22 · 2015: 18 · 2014: 15 · 2013: 22 · 2012: 8
FWCI: 0.81
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Cell Biology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
PMC
Funders: National Institute of General Medical Sciences (P50GM068763)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Chemical and Physical Studies
Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
Keywords: mucus, extracellular matrix, nuclear pores, biopolymer gels, particle transport, size exclusion
MeSH terms: Animals, Bacteria, Cell Adhesion, Cell Membrane Permeability, Diffusion, Extracellular Matrix, Lipid Bilayers, Mammals, Mucus, Bacterial Physiological Phenomena, Biofilms, Hydrogels, Protein Transport, Nuclear Pore, Cell Proliferation

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