ACS Publications. Most Trusted. Most Cited. Most Read
Size-Limited Penetration of Nanoparticles into Porcine Respiratory Mucus after Aerosol Deposition
My Activity

Figure 1Loading Img
    Article

    Size-Limited Penetration of Nanoparticles into Porcine Respiratory Mucus after Aerosol Deposition
    Click to copy article linkArticle link copied!

    View Author Information
    ‡ ∥ Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, and Experimental Physics, Saarland University, 66123 Saarbruecken, Germany
    § Institute for Mechanical Process Engineering and Mechanics, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany
    *E-mail: [email protected]. Tel.: +49 681 98806-1000.
    Other Access OptionsSupporting Information (4)

    Biomacromolecules

    Cite this: Biomacromolecules 2016, 17, 4, 1536–1542
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biomac.6b00164
    Published March 9, 2016
    Copyright © 2016 American Chemical Society

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    We investigated the rheological properties and the penetration of differently sized carboxylated nanoparticles in pig pulmonary mucus, on different distance and time scales. Nanoparticles were either mechanically mixed into the mucus samples or deposited as an aerosol, the latter resembling a more physiologically relevant delivery scenario. After mechanical dispersion, 500 nm particles were locally trapped; a fraction of carboxylated tracer particles of 100 or 200 nm in diameter could however freely diffuse in these networks over distances of approximately 20 μm. In contrast, after aerosol deposition on top of the mucus layer only particles with a size of 100 nm were able to penetrate into mucus, suggesting the presence of smaller pores at the air-mucus interface compared to within mucus. These findings are relevant to an understanding of the fate of potentially harmful aerosol particles, such as pathogens, pollutants, and other nanomaterials after incidental inhalation, as well as for the design of pulmonary drug delivery systems.

    Copyright © 2016 American Chemical Society

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.6b00164.

    • Calibration curves showing a strong linear correlation between the concentration and fluorescence intensity of the fluorescently labeled particles; Comparison of the MSD plots of 100, 200, and 500 nm carboxylated nanoparticles in fresh pulmonary pig mucus, versus pig mucus stored at −20 °C and thawed gradually (PDF).

    • Video-recording of 100 nm COOH-modified particles in native porcine pulmonary mucus (MPG).

    • Video-recording of 200 nm COOH-modified particles in native porcine pulmonary mucus (MPG).

    • Video-recording of 500 nm COOH-modified particles in native porcine pulmonary mucus (MPG).

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai

    This article is cited by 114 publications.

    1. Burcu Okmen Altas, Gokce Dicle Kalaycioglu, Sapir Lifshiz-Simon, Yeshayahu Talmon, Nihal Aydogan. Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability. Molecular Pharmaceutics 2024, 21 (2) , 633-650. https://doi.org/10.1021/acs.molpharmaceut.3c00773
    2. Mingze Xu, Yuming Qi, Gaoshuo Liu, Yuanqing Song, Xingya Jiang, Bujie Du. Size-Dependent In Vivo Transport of Nanoparticles: Implications for Delivery, Targeting, and Clearance. ACS Nano 2023, 17 (21) , 20825-20849. https://doi.org/10.1021/acsnano.3c05853
    3. Leah Wright, Paul Joyce, Timothy J Barnes, Clive A Prestidge. Mimicking the Gastrointestinal Mucus Barrier: Laboratory-Based Approaches to Facilitate an Enhanced Understanding of Mucus Permeation. ACS Biomaterials Science & Engineering 2023, 9 (6) , 2819-2837. https://doi.org/10.1021/acsbiomaterials.1c00814
    4. Yiyang Guo, Yubin Ma, Xin Chen, Min Li, Xuehu Ma, Gang Cheng, Changying Xue, Yi Y. Zuo, Bingbing Sun. Mucus Penetration of Surface-Engineered Nanoparticles in Various pH Microenvironments. ACS Nano 2023, 17 (3) , 2813-2828. https://doi.org/10.1021/acsnano.2c11147
    5. Dipesh Dinanath Pednekar, Madison A. Liguori, Claudia N. H. Marques, Teng Zhang, Nan Zhang, Zejian Zhou, Kagya Amoako, Huan Gu. From Static to Dynamic: A Review on the Role of Mucus Heterogeneity in Particle and Microbial Transport. ACS Biomaterials Science & Engineering 2022, 8 (7) , 2825-2848. https://doi.org/10.1021/acsbiomaterials.2c00182
    6. Jeffrey Watchorn, Aaron J. Clasky, Gayatri Prakash, Ian A. E. Johnston, Paul Z. Chen, Frank X. Gu. Untangling Mucosal Drug Delivery: Engineering, Designing, and Testing Nanoparticles to Overcome the Mucus Barrier. ACS Biomaterials Science & Engineering 2022, 8 (4) , 1396-1426. https://doi.org/10.1021/acsbiomaterials.2c00047
    7. V. H. Giang Phan, Huu Thuy Trang Duong, Phu-Tri Tran, Thavasyappan Thambi, Duy-Khiet Ho, Xabier Murgia. Self-Assembled Amphiphilic Starch Based Drug Delivery Platform: Synthesis, Preparation, and Interactions with Biological Barriers. Biomacromolecules 2021, 22 (2) , 572-585. https://doi.org/10.1021/acs.biomac.0c01430
    8. Jennifer L. Schiller, Samuel K. Lai. Tuning Barrier Properties of Biological Hydrogels. ACS Applied Bio Materials 2020, 3 (5) , 2875-2890. https://doi.org/10.1021/acsabm.0c00187
    9. Benedikt C. Huck, Olga Hartwig, Alexander Biehl, Konrad Schwarzkopf, Christian Wagner, Brigitta Loretz, Xabier Murgia, Claus-Michael Lehr. Macro- and Microrheological Properties of Mucus Surrogates in Comparison to Native Intestinal and Pulmonary Mucus. Biomacromolecules 2019, 20 (9) , 3504-3512. https://doi.org/10.1021/acs.biomac.9b00780
    10. Duy-Khiet Ho, Sarah Frisch, Alexander Biehl, Emmanuel Terriac, Chiara De Rossi, Konrad Schwarzkopf, Franziska Lautenschläger, Brigitta Loretz, Xabier Murgia, Claus-Michael Lehr. Farnesylated Glycol Chitosan as a Platform for Drug Delivery: Synthesis, Characterization, and Investigation of Mucus–Particle Interactions. Biomacromolecules 2018, 19 (8) , 3489-3501. https://doi.org/10.1021/acs.biomac.8b00795
    11. Duy-Khiet Ho, Ana Costa, Chiara De Rossi, Cristiane de Souza Carvalho-Wodarz, Brigitta Loretz, Claus-Michael Lehr. Polysaccharide Submicrocarrier for Improved Pulmonary Delivery of Poorly Soluble Anti-infective Ciprofloxacin: Preparation, Characterization, and Influence of Size on Cellular Uptake. Molecular Pharmaceutics 2018, 15 (3) , 1081-1096. https://doi.org/10.1021/acs.molpharmaceut.7b00967
    12. Lu Su, Richen Li, Sarosh Khan, Ryan Clanton, Fuwu Zhang, Yen-Nan Lin, Yue Song, Hai Wang, Jingwei Fan, Soleil Hernandez, Andrew S. Butters, Gamal Akabani, Ronan MacLoughlin, Justin Smolen, and Karen L. Wooley . Chemical Design of Both a Glutathione-Sensitive Dimeric Drug Guest and a Glucose-Derived Nanocarrier Host to Achieve Enhanced Osteosarcoma Lung Metastatic Anticancer Selectivity. Journal of the American Chemical Society 2018, 140 (4) , 1438-1446. https://doi.org/10.1021/jacs.7b11462
    13. Caroline E. Wagner, Bradley S. Turner, Michael Rubinstein, Gareth H. McKinley, and Katharina Ribbeck . A Rheological Study of the Association and Dynamics of MUC5AC Gels. Biomacromolecules 2017, 18 (11) , 3654-3664. https://doi.org/10.1021/acs.biomac.7b00809
    14. Elias Haddad, Eric A. Ben-David, Maryana Habiby, Dror L. Angel, Andy M. Booth, Isam Sabbah. Enhancing nano and microplastics destabilization: Synergistic effects of natural mucin and conventional coagulants in water and wastewater treatment. Environmental Technology & Innovation 2025, 38 , 104189. https://doi.org/10.1016/j.eti.2025.104189
    15. Pouria Savadi, Andrea Casale, Michele Roggia, Gemma Conte, M. Victoria Lozano, Gabriella Costabile, Francesca Ungaro, Sandro Cosconati, Manuel Santander-Ortega, Ivana d’Angelo. Unveiling the role of poly(vinyl alcohol) in the production of mucus-penetrating PLGA nanoparticles. International Journal of Pharmaceutics 2025, 673 , 125398. https://doi.org/10.1016/j.ijpharm.2025.125398
    16. Hojjatollah Nazari, Reza Akbari Asbagh, Parichehr Abasipanah, Zakiye Nazari, Majid Ebrahimi Warkiani. Microfluidics in the diagnosis, treatment, and drug delivery of chronic respiratory disorders: Advancements and potential applications. 2025, 209-265. https://doi.org/10.1016/B978-0-443-27345-2.00007-2
    17. Robyn A Macartney, Abijit Das, Atina G Imaniyyah, Annabelle TR Fricker, Andrew M Smith, Stefano Fedele, Ipsita Roy, Hae-Won Kim, Dongjoon Lee, Jonathan C Knowles. In vitro and ex vivo models of the oral mucosa as platforms for the validation of novel drug delivery systems. Journal of Tissue Engineering 2025, 16 https://doi.org/10.1177/20417314241313458
    18. Pooja Jain, Foziyah Zakir, Manvi Singh, Mamta Bishnoi, Bushra Ahmad, Zeenat Iqbal. Lipid-based drug delivery for pulmonary microbial infections. 2025, 233-253. https://doi.org/10.1016/B978-0-443-22374-7.00011-6
    19. Jaka Levanič, Ilja Gasan Osojnik Črnivec, Iza Rozman, Mihaela Skrt, Alja Štern, Bojana Žegura, Nataša Poklar Ulrih. Nano spray-dried particles of in-situ crosslinked alginate and their toxicological characterisation. International Journal of Biological Macromolecules 2024, 283 , 137750. https://doi.org/10.1016/j.ijbiomac.2024.137750
    20. Lishan Xiong, Xinyuan Li, Xiaojie Lu, Zhendong Zhang, Yan Zhang, Wen Wu, Chenhui Wang. Inhaled multilevel size-tunable, charge-reversible and mucus-traversing composite microspheres as trojan horse: Enhancing lung deposition and tumor penetration. Chinese Chemical Letters 2024, 35 (9) , 109384. https://doi.org/10.1016/j.cclet.2023.109384
    21. Jianqing Peng, Qin Wang, Runbin Sun, Ke Zhang, Yi Chen, Zipeng Gong. Phospholipids of inhaled liposomes determine the in vivo fate and therapeutic effects of salvianolic acid B on idiopathic pulmonary fibrosis. Journal of Controlled Release 2024, 371 , 1-15. https://doi.org/10.1016/j.jconrel.2024.05.026
    22. Leonardo Martin‐Alarcon, Aleksandra Govedarica, Randy H. Ewoldt, Steven L. Bryant, Gregory D. Jay, Tannin A. Schmidt, Milana Trifkovic. Scale‐Dependent Rheology of Synovial Fluid Lubricating Macromolecules. Small 2024, 20 (21) https://doi.org/10.1002/smll.202306207
    23. Falin Tian, Xinghua Shi. Experimental and Theoretical Studies of Transport of Nanoparticles in Mucosal Tissues. 2024, 245-279. https://doi.org/10.1002/9783527839568.ch10
    24. Yaoxing Chen, Chenyun Zhang, Yukun Huang, Yuxiao Ma, Qingxiang Song, Hongzhuan Chen, Gan Jiang, Xiaoling Gao. Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway. Advanced Drug Delivery Reviews 2024, 207 , 115196. https://doi.org/10.1016/j.addr.2024.115196
    25. Neha Raina, Meghna Singh, Radha Rani, Ayushi Garg, Ajay Sharma, Pramod Kumar, Madhu Gupta. Polymeric micelles for drug delivery: properties, designs and applications. 2024, 289-326. https://doi.org/10.1016/B978-0-12-819979-4.00006-4
    26. Yingshan Zhao, Jie Hu, Yuancheng Ke, Qinqiang Long, Jinlan Mao, Huihui Li, Zhenping Xiao, Kangyiran Pan, Siying Yuan, Jiayi Xue, Wei Li, Meiju Zhong, Linquan Zang, Shijie Wei, Dongzhi Hou. Micro-interaction of montmorillonite-loaded nanoparticles with mucin promotes retention of betaxolol hydrochloride on the ocular surface and the tear film microenvironment. Applied Clay Science 2024, 247 , 107198. https://doi.org/10.1016/j.clay.2023.107198
    27. Mengjun Zhang, Haoyu Lu, Liangkun Xie, Xulu Liu, Dongmei Cun, Mingshi Yang. Inhaled RNA drugs to treat lung diseases: Disease-related cells and nano–bio interactions. Advanced Drug Delivery Reviews 2023, 203 , 115144. https://doi.org/10.1016/j.addr.2023.115144
    28. Kaitlyn R. Rouillard, Matthew R. Markovetz, William J. Kissner, William L. Boone, Lucas M. Plott, David B. Hill. Altering the viscoelastic properties of mucus-grown Pseudomonas aeruginosa biofilms affects antibiotic susceptibility. Biofilm 2023, 5 , 100104. https://doi.org/10.1016/j.bioflm.2023.100104
    29. Enkeleda Meziu, Kristela Shehu, Marcus Koch, Marc Schneider, Annette Kraegeloh. Impact of mucus modulation by N-acetylcysteine on nanoparticle toxicity. International Journal of Pharmaceutics: X 2023, 6 , 100212. https://doi.org/10.1016/j.ijpx.2023.100212
    30. Aghiad Bali, Mohamed A. M. Kamal, Glorjen Mulla, Brigitta Loretz, Claus‐Michael Lehr. Functional Materials to Overcome Bacterial Barriers and Models to Advance Their Development. Advanced Functional Materials 2023, 33 (45) https://doi.org/10.1002/adfm.202304370
    31. Zhaokui Jin, Qi Gao, Keke Wu, Jiang Ouyang, Weisheng Guo, Xing-Jie Liang. Harnessing inhaled nanoparticles to overcome the pulmonary barrier for respiratory disease therapy. Advanced Drug Delivery Reviews 2023, 202 , 115111. https://doi.org/10.1016/j.addr.2023.115111
    32. Baozhen Zhang, Lizhen Zhu, Hong Pan, Lintao Cai. Biocompatible smart micro/nanorobots for active gastrointestinal tract drug delivery. Expert Opinion on Drug Delivery 2023, 20 (10) , 1427-1441. https://doi.org/10.1080/17425247.2023.2270915
    33. Ludan Yue, Xueyang Zhang, Chenchen Zhao, Rongchang Chen, Xiaoyuan Chen, Lang Rao. Inhaled drug delivery: Past, present, and future. Nano Today 2023, 52 , 101942. https://doi.org/10.1016/j.nantod.2023.101942
    34. Mojtaba Falahati, Anwarul Hasan, Hojjat Alizadeh Zeinabad, Vahid Serpooshan, J.H. von der Thüsen, Timo L.M. ten Hagen. Engineering of pulmonary surfactant corona on inhaled nanoparticles to operate in the lung system. Nano Today 2023, 52 , 101998. https://doi.org/10.1016/j.nantod.2023.101998
    35. Xin Yan, Xianyi Sha. Nanoparticle-Mediated Strategies for Enhanced Drug Penetration and Retention in the Airway Mucosa. Pharmaceutics 2023, 15 (10) , 2457. https://doi.org/10.3390/pharmaceutics15102457
    36. Edgar Barajas-Ledesma, Chris Holland. Probing the compositional and rheological properties of gastropod locomotive mucus. Frontiers in Soft Matter 2023, 3 https://doi.org/10.3389/frsfm.2023.1201511
    37. NANGUDE SATISH, RAVINDRA KAMBLE, VANHERE KAJAL. IN VITRO MUCOLYTIC ACTIVITY DETERMINATION OF N-ACETYL CYSTEINE EFFERVESCENT TABLET USING SUSPENDED LEVEL VISCOMETER. International Journal of Applied Pharmaceutics 2023, , 141-144. https://doi.org/10.22159/ijap.2023v15i5.48069
    38. Nicole A. Bustos, Katharina Ribbeck, Caroline E. Wagner. The role of mucosal barriers in disease progression and transmission. Advanced Drug Delivery Reviews 2023, 200 , 115008. https://doi.org/10.1016/j.addr.2023.115008
    39. Chelsea Cary, Phoebe Stapleton. Determinants and mechanisms of inorganic nanoparticle translocation across mammalian biological barriers. Archives of Toxicology 2023, 97 (8) , 2111-2131. https://doi.org/10.1007/s00204-023-03528-x
    40. Shuhao Zhang, Chaoran Zhu, Wanting Huang, Hua Liu, Mingzhu Yang, Xuejiao Zeng, Zhenzhong Zhang, Junjie Liu, Jinjin Shi, Yurong Hu, Xiufang Shi, Zhi-Hao Wang. Recent progress of micro/nanomotors to overcome physiological barriers in the gastrointestinal tract. Journal of Controlled Release 2023, 360 , 514-527. https://doi.org/10.1016/j.jconrel.2023.07.005
    41. Vincent Lenders, Xanthippi Koutsoumpou, Philana Phan, Stefaan J. Soenen, Karel Allegaert, Steven de Vleeschouwer, Jaan Toelen, Zongmin Zhao, Bella B. Manshian. Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport. Chemical Society Reviews 2023, 52 (14) , 4672-4724. https://doi.org/10.1039/D1CS00574J
    42. Phoebe A. Stapleton. The Application of Engineered Nanomaterials in Perinatal Therapeutics. Small 2023, 4 https://doi.org/10.1002/smll.202303072
    43. Rhianna E Lee, Boris Reidel, Mark R Nelson, Jade K Macdonald, Mehmet Kesimer, Scott H Randell. Air-Liquid interface cultures to model drug delivery through the mucociliary epithelial barrier. Advanced Drug Delivery Reviews 2023, 198 , 114866. https://doi.org/10.1016/j.addr.2023.114866
    44. Federica De Gaetano, Consuelo Celesti, Giuseppe Paladini, Valentina Venuti, Maria Chiara Cristiano, Donatella Paolino, Daniela Iannazzo, Vincenza Strano, Anna M. Gueli, Silvana Tommasini, Cinzia Anna Ventura, Rosanna Stancanelli. Solid Lipid Nanoparticles Containing Morin: Preparation, Characterization, and Ex Vivo Permeation Studies. Pharmaceutics 2023, 15 (6) , 1605. https://doi.org/10.3390/pharmaceutics15061605
    45. Eric A. Ben-David, Maryana Habibi, Elias Haddad, Marei Sammar, Dror L. Angel, Hila Dror, Haim Lahovitski, Andy M. Booth, Isam Sabbah. Mechanism of nanoplastics capture by jellyfish mucin and its potential as a sustainable water treatment technology. Science of The Total Environment 2023, 869 , 161824. https://doi.org/10.1016/j.scitotenv.2023.161824
    46. Thomas Sécher, Nathalie Heuzé-Vourc’h. Pulmonary Delivery of Antibody for the Treatment of Respiratory Diseases. 2023, 21-51. https://doi.org/10.1007/978-3-031-47567-2_2
    47. Indhumathi Thirugnanasambandham, Kalaiselvi Aasaithambi, Imrankhan Nizam, Gowthamarajan Kuppusamy. Stability of Polymeric Micelles and Their Regulatory Status. 2023, 277-294. https://doi.org/10.1007/978-981-99-0361-0_15
    48. Morvarid Saeinasab, Mohamed Abdul-Al, Farshid Sefat. Encapsulation in respiratory system. 2023, 283-298. https://doi.org/10.1016/B978-0-12-824345-9.00012-X
    49. Dan Yuan, Feibai Zhou, Zhicheng Niu, Penghui Shen, Mouming Zhao. Formation of mucus-permeable nanoparticles from soy protein isolate by partial enzymatic hydrolysis coupled with thermal and pH-shifting treatment. Food Chemistry 2023, 398 , 133851. https://doi.org/10.1016/j.foodchem.2022.133851
    50. M. N. Lavanya, R. Preethi, J. A. Moses, C. Anandharamakrishnan. Aerosol-based Pulmonary Delivery of Therapeutic Molecules from Food Sources: Delivery Mechanism, Research Trends, and the Way Forward. Food Reviews International 2022, 38 (sup1) , 753-788. https://doi.org/10.1080/87559129.2021.1888971
    51. Yaxin Cui, Tianyu Zhu, Xueyan Zhang, Jicong Chen, Fengying Sun, Youxin Li, Lesheng Teng. Oral delivery of superoxide dismutase by lipid polymer hybrid nanoparticles for the treatment of ulcerative colitis. Chinese Chemical Letters 2022, 33 (10) , 4617-4622. https://doi.org/10.1016/j.cclet.2022.03.077
    52. Liu Liu, Wenxuan Cao, Mengqiu Xia, Chunling Tian, Wenqing Wu, Ye Cai, Xiaoqin Chu. Self-Emulsifying Drug Delivery System Enhances Tissue Distribution of Cinnamaldehyde by Altering the Properties of the Mucus Layer. AAPS PharmSciTech 2022, 23 (7) https://doi.org/10.1208/s12249-022-02416-4
    53. Peter Fischer. Rheology of Mucins. 2022, 3-1-3-36. https://doi.org/10.1063/9780735424715_003
    54. Wenhao Wang, Zhengwei Huang, Ying Huang, Xuejuan Zhang, Jiayuan Huang, Yingtong Cui, Xiao Yue, Cheng Ma, Fangqin Fu, Wenhua Wang, Chuanbin Wu, Xin Pan. Pulmonary delivery nanomedicines towards circumventing physiological barriers: Strategies and characterization approaches. Advanced Drug Delivery Reviews 2022, 185 , 114309. https://doi.org/10.1016/j.addr.2022.114309
    55. Domizia Baldassi, Shubhankar Ambike, Martin Feuerherd, Cho-Chin Cheng, David J. Peeler, Daniel P. Feldmann, Diana Leidy Porras-Gonzalez, Xin Wei, Lea-Adriana Keller, Nikolaus Kneidinger, Mircea Gabriel Stoleriu, Andreas Popp, Gerald Burgstaller, Suzie H. Pun, Thomas Michler, Olivia M. Merkel. Inhibition of SARS-CoV-2 replication in the lung with siRNA/VIPER polyplexes. Journal of Controlled Release 2022, 345 , 661-674. https://doi.org/10.1016/j.jconrel.2022.03.051
    56. Benedikt C. Huck, Xabier Murgia, Sarah Frisch, Marius Hittinger, Alberto Hidalgo, Brigitta Loretz, Claus-Michael Lehr. Models using native tracheobronchial mucus in the context of pulmonary drug delivery research: Composition, structure and barrier properties. Advanced Drug Delivery Reviews 2022, 183 , 114141. https://doi.org/10.1016/j.addr.2022.114141
    57. Esther H Roh, Catherine A Fromen, Millicent O Sullivan. Inhalable mRNA vaccines for respiratory diseases: a roadmap. Current Opinion in Biotechnology 2022, 74 , 104-109. https://doi.org/10.1016/j.copbio.2021.10.017
    58. Mario Di Gioacchino, Luca Di Giampaolo, Rocco Mangifesta, Sebastiano Gangemi, Claudia Petrarca. Exposure to nanoparticles and occupational allergy. Current Opinion in Allergy & Clinical Immunology 2022, 22 (2) , 55-63. https://doi.org/10.1097/ACI.0000000000000818
    59. Li Zhang, Hriday Bera, Hengzhuang Wang, Junwei Wang, Yi Guo, Changzhi Shi, Dongmei Cun, Claus Moser, Niels Høiby, Mingshi Yang. Combination and nanotechnology based pharmaceutical strategies for combating respiratory bacterial biofilm infections. International Journal of Pharmaceutics 2022, 616 , 121507. https://doi.org/10.1016/j.ijpharm.2022.121507
    60. Guiting Huang, Shuyuan Shuai, Weicheng Zhou, Yingchong Chen, Baode Shen, Pengfei Yue. To Enhance Mucus Penetration and Lung Absorption of Drug by Inhalable Nanocrystals-In-Microparticles. Pharmaceutics 2022, 14 (3) , 538. https://doi.org/10.3390/pharmaceutics14030538
    61. Thomas Sonntag, Mickael Rapp, Pascal Didier, Luc Lebeau, Françoise Pons, Anne Casset. Mucus-producing epithelial models for investigating the activity of gene delivery systems in the lung. International Journal of Pharmaceutics 2022, 614 , 121423. https://doi.org/10.1016/j.ijpharm.2021.121423
    62. Benjamin J. Lee, Yahya Cheema, Shahed Bader, Gregg A. Duncan. Shaping nanoparticle diffusion through biological barriers to drug delivery. JCIS Open 2021, 4 , 100025. https://doi.org/10.1016/j.jciso.2021.100025
    63. Chang Liu, Xiaohe Jiang, Yong Gan, Miaorong Yu. Engineering nanoparticles to overcome the mucus barrier for drug delivery: Design, evaluation and state-of-the-art. Medicine in Drug Discovery 2021, 12 , 100110. https://doi.org/10.1016/j.medidd.2021.100110
    64. Milad Radiom, Romain Hénault, Salma Mani, Aline Grein Iankovski, Xavier Norel, Jean-François Berret. Magnetic wire active microrheology of human respiratory mucus. Soft Matter 2021, 17 (32) , 7585-7595. https://doi.org/10.1039/D1SM00512J
    65. Wenhao Zhong, Xinyu Zhang, Yunxin Zeng, Dongjun Lin, Jun Wu. Recent applications and strategies in nanotechnology for lung diseases. Nano Research 2021, 14 (7) , 2067-2089. https://doi.org/10.1007/s12274-020-3180-3
    66. Sarah Frisch, Annette Boese, Benedikt Huck, Justus C Horstmann, Duy-Khiet Ho, Konrad Schwarzkopf, Xabier Murgia, Brigitta Loretz, Cristiane de Souza Carvalho-Wodarz, Claus-Michael Lehr. A pulmonary mucus surrogate for investigating antibiotic permeation and activity against Pseudomonas aeruginosa biofilms. Journal of Antimicrobial Chemotherapy 2021, 76 (6) , 1472-1479. https://doi.org/10.1093/jac/dkab068
    67. Daiqin Chen, Jinhao Liu, Jerry Wu, Jung Soo Suk. Enhancing nanoparticle penetration through airway mucus to improve drug delivery efficacy in the lung. Expert Opinion on Drug Delivery 2021, 18 (5) , 595-606. https://doi.org/10.1080/17425247.2021.1854222
    68. Maria João Bessa, Fátima Brandão, Paul Fokkens, Flemming R. Cassee, Apostolos Salmatonidis, Mar Viana, Adriana Vulpoi, Simion Simon, Eliseo Monfort, João Paulo Teixeira, Sónia Fraga. Toxicity assessment of industrial engineered and airborne process-generated nanoparticles in a 3D human airway epithelial in vitro model. Nanotoxicology 2021, 15 (4) , 542-557. https://doi.org/10.1080/17435390.2021.1897698
    69. M. Ghezzi, S. Pescina, C. Padula, P. Santi, E. Del Favero, L. Cantù, S. Nicoli. Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions. Journal of Controlled Release 2021, 332 , 312-336. https://doi.org/10.1016/j.jconrel.2021.02.031
    70. Gregor Peters, Olaf Wendler, David Böhringer, Antoniu-Oreste Gostian, Sarina K. Müller, Herbert Canziani, Nicolas Hesse, Marion Semmler, David A. Berry, Stefan Kniesburges, Wolfgang Peukert, Michael Döllinger. Human Laryngeal Mucus from the Vocal Folds: Rheological Characterization by Particle Tracking Microrheology and Oscillatory Shear Rheology. Applied Sciences 2021, 11 (7) , 3011. https://doi.org/10.3390/app11073011
    71. E. Meziu, M. Koch, J. Fleddermann, K. Schwarzkopf, M. Schneider, A. Kraegeloh. Visualization of the structure of native human pulmonary mucus. International Journal of Pharmaceutics 2021, 597 , 120238. https://doi.org/10.1016/j.ijpharm.2021.120238
    72. Tanmay Padhye, Kavya Sree Maravajjala, Karnam Laxmi Swetha, Swati Sharma, Aniruddha Roy. A comprehensive review of the strategies to improve oral drug absorption with special emphasis on the cellular and molecular mechanisms. Journal of Drug Delivery Science and Technology 2021, 61 , 102178. https://doi.org/10.1016/j.jddst.2020.102178
    73. Zachary Enlo-Scott, Magda Swedrowska, Ben Forbes. Epithelial permeability and drug absorption in the lungs. 2021, 267-299. https://doi.org/10.1016/B978-0-12-814974-4.00004-3
    74. Hanyu Liu, Xinyue Han, Huamei Li, Qi Tao, Jie Hu, Shuo Liu, Huaixin Liu, Jun Zhou, Wei Li, Fan Yang, Qineng Ping, Shijie Wei, Hongmei Liu, Huaqing Lin, Dongzhi Hou. Wettability and contact angle affect precorneal retention and pharmacodynamic behavior of microspheres. Drug Delivery 2021, 28 (1) , 2011-2023. https://doi.org/10.1080/10717544.2021.1981493
    75. Rosy Ghanem, Véronique Laurent, Philippe Roquefort, Tanguy Haute, Sophie Ramel, Tony Le Gall, Thierry Aubry, Tristan Montier. Optimizations of In Vitro Mucus and Cell Culture Models to Better Predict In Vivo Gene Transfer in Pathological Lung Respiratory Airways: Cystic Fibrosis as an Example. Pharmaceutics 2021, 13 (1) , 47. https://doi.org/10.3390/pharmaceutics13010047
    76. Xabier Murgia, Andreas M. Kany, Christian Herr, Duy-Khiet Ho, Chiara De Rossi, Robert Bals, Claus-Michael Lehr, Anna K. H. Hirsch, Rolf W. Hartmann, Martin Empting, Teresa Röhrig. Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection. Scientific Reports 2020, 10 (1) https://doi.org/10.1038/s41598-020-73459-5
    77. Duy-Khiet Ho, Rebekka Christmann, Xabier Murgia, Chiara De Rossi, Sarah Frisch, Marcus Koch, Ulrich F. Schaefer, Brigitta Loretz, Didier Desmaele, Patrick Couvreur, Claus-Michael Lehr. Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform. Frontiers in Chemistry 2020, 8 https://doi.org/10.3389/fchem.2020.584242
    78. Johanna Hafner, Claude Oelschlaeger, Norbert Willenbacher. Microrheology imaging of fiber suspensions – a case study for lyophilized collagen I in HCl solutions. Soft Matter 2020, 16 (39) , 9014-9027. https://doi.org/10.1039/D0SM01096K
    79. Roni Sverdlov Arzi, Alejandro Sosnik, Noy Cohen. A Microscopically Motivated Model for Particle Penetration into Swollen Biological Networks. Polymers 2020, 12 (9) , 1912. https://doi.org/10.3390/polym12091912
    80. Hessel van der Weide, Unai Cossío, Raquel Gracia, Yvonne M. te Welscher, Marian T. ten Kate, Aart van der Meijden, Marco Marradi, Jeffrey A. S. Ritsema, Denise M. C. Vermeulen-de Jongh, Gert Storm, Wil H. F. Goessens, Iraida Loinaz, Cornelus F. van Nostrum, Jordi Llop, John P. Hays, Irma A. J. M. Bakker-Woudenberg. Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats. Antimicrobial Agents and Chemotherapy 2020, 64 (9) https://doi.org/10.1128/AAC.00517-20
    81. Ankur Sharma, Kalpesh Vaghasiya, Pushpa Gupta, Amit Kumar Singh, Umesh Datta Gupta, Rahul Kumar Verma. Dynamic mucus penetrating microspheres for efficient pulmonary delivery and enhanced efficacy of host defence peptide (HDP) in experimental tuberculosis. Journal of Controlled Release 2020, 324 , 17-33. https://doi.org/10.1016/j.jconrel.2020.05.013
    82. Ryan X. Ward, Trevor B. Tilly, Syeda Irsa Mazhar, Sarah E. Robinson, Arantzazu Eiguren-Fernandez, Jun Wang, Tara Sabo-Attwood, Chang-Yu Wu. Mimicking the human respiratory system: Online in vitro cell exposure for toxicity assessment of welding fume aerosol. Journal of Hazardous Materials 2020, 395 , 122687. https://doi.org/10.1016/j.jhazmat.2020.122687
    83. José das Neves, Roni Sverdlov Arzi, Alejandro Sosnik. Molecular and cellular cues governing nanomaterial–mucosae interactions: from nanomedicine to nanotoxicology. Chemical Society Reviews 2020, 49 (14) , 5058-5100. https://doi.org/10.1039/C8CS00948A
    84. Gokce Alp, Nihal Aydogan. Lipid-based mucus penetrating nanoparticles and their biophysical interactions with pulmonary mucus layer. European Journal of Pharmaceutics and Biopharmaceutics 2020, 149 , 45-57. https://doi.org/10.1016/j.ejpb.2020.01.017
    85. Shayan M. Vanaki, David Holmes, Kabir Suara, Pahala Gedara Jayathilake, Richard Brown. Transport and fate of inhaled particles after deposition onto the airway surface liquid: A 3D numerical study. Computers in Biology and Medicine 2020, 117 , 103595. https://doi.org/10.1016/j.compbiomed.2019.103595
    86. Safar Alqahtani, Clive J. Roberts, Snjezana Stolnik, Cynthia Bosquillon. Development of an In Vitro System to Study the Interactions of Aerosolized Drugs with Pulmonary Mucus. Pharmaceutics 2020, 12 (2) , 145. https://doi.org/10.3390/pharmaceutics12020145
    87. Aljoscha Koenneke, Marcel Pourasghar, Marc Schneider. Nano-structured microparticles for inhalation. 2020, 119-160. https://doi.org/10.1016/B978-0-12-817776-1.00006-7
    88. Joscelyn C. Mejías, Krishnendu Roy. In-vitro and in-vivo characterization of a multi-stage enzyme-responsive nanoparticle-in-microgel pulmonary drug delivery system. Journal of Controlled Release 2019, 316 , 393-403. https://doi.org/10.1016/j.jconrel.2019.09.012
    89. Duy-Khiet Ho, Brittany L.B. Nichols, Kevin J. Edgar, Xabier Murgia, Brigitta Loretz, Claus-Michael Lehr. Challenges and strategies in drug delivery systems for treatment of pulmonary infections. European Journal of Pharmaceutics and Biopharmaceutics 2019, 144 , 110-124. https://doi.org/10.1016/j.ejpb.2019.09.002
    90. Sarah Zellnitz, Eva Roblegg, Joana Pinto, Eleonore Fröhlich. Delivery of Dry Powders to the Lungs: Influence of Particle Attributes from a Biological and Technological Point of View. Current Drug Delivery 2019, 16 (3) , 180-194. https://doi.org/10.2174/1567201815666181024143249
    91. Nicole Schneider-Daum, Marius Hittinger, Xabier Murgia, Claus-Michael Lehr. Cellular and Non-cellular Barriers to Particle Transport Across the Lungs. 2019, 171-189. https://doi.org/10.1007/978-3-030-12461-8_7
    92. Katherine A. Roach, Aleksandr B. Stefaniak, Jenny R. Roberts. Metal nanomaterials: Immune effects and implications of physicochemical properties on sensitization, elicitation, and exacerbation of allergic disease. Journal of Immunotoxicology 2019, 16 (1) , 87-124. https://doi.org/10.1080/1547691X.2019.1605553
    93. Nashrawan Lababidi, Valentin Sigal, Aljoscha Koenneke, Konrad Schwarzkopf, Andreas Manz, Marc Schneider. Microfluidics as tool to prepare size-tunable PLGA nanoparticles with high curcumin encapsulation for efficient mucus penetration. Beilstein Journal of Nanotechnology 2019, 10 , 2280-2293. https://doi.org/10.3762/bjnano.10.220
    94. Matthias Marczynski, Benjamin T. Käsdorf, Bernhard Altaner, Andreas Wenzler, Ulrich Gerland, Oliver Lieleg. Transient binding promotes molecule penetration into mucin hydrogels by enhancing molecular partitioning. Biomaterials Science 2018, 6 (12) , 3373-3387. https://doi.org/10.1039/C8BM00664D
    95. C.E. Wagner, K.M. Wheeler, K. Ribbeck. Mucins and Their Role in Shaping the Functions of Mucus Barriers. Annual Review of Cell and Developmental Biology 2018, 34 (1) , 189-215. https://doi.org/10.1146/annurev-cellbio-100617-062818
    96. Donglei Leng, Kaushik Thanki, Elias Fattal, Camilla Foged, Mingshi Yang. Engineering of budesonide-loaded lipid-polymer hybrid nanoparticles using a quality-by-design approach. International Journal of Pharmaceutics 2018, 548 (2) , 740-746. https://doi.org/10.1016/j.ijpharm.2017.08.094
    97. Sergey Zaichik, Christian Steinbring, Claudia Menzel, Ludwig Knabl, Dorothea Orth-Höller, Helmut Ellemunter, Katharina Niedermayr, Andreas Bernkop-Schnürch. Development of self-emulsifying drug delivery systems (SEDDS) for ciprofloxacin with improved mucus permeating properties. International Journal of Pharmaceutics 2018, 547 (1-2) , 282-290. https://doi.org/10.1016/j.ijpharm.2018.06.005
    98. Enrica Chiesa, Rossella Dorati, Bice Conti, Tiziana Modena, Emanuela Cova, Federica Meloni, Ida Genta. Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus. International Journal of Molecular Sciences 2018, 19 (8) , 2310. https://doi.org/10.3390/ijms19082310
    99. Franci Bajd, Igor Serša. A Bond-Fluctuation Model of Translational Dynamics of Chain-like Particles through Mucosal Scaffolds. Biophysical Journal 2018, 114 (11) , 2732-2742. https://doi.org/10.1016/j.bpj.2018.04.031
    100. Joël Bourquin, Ana Milosevic, Daniel Hauser, Roman Lehner, Fabian Blank, Alke Petri‐Fink, Barbara Rothen‐Rutishauser. Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials. Advanced Materials 2018, 30 (19) https://doi.org/10.1002/adma.201704307
    Load all citations

    Biomacromolecules

    Cite this: Biomacromolecules 2016, 17, 4, 1536–1542
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biomac.6b00164
    Published March 9, 2016
    Copyright © 2016 American Chemical Society

    Article Views

    2239

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.