Abstract
Mucin glycoproteins are ideal biomacromolecules for drug delivery applications since they naturally offer a plethora of different functional groups that can engage in specific and unspecific binding interactions with cargo molecules. However, to fabricate drug carrier objects from mucins, suitable stabilization mechanisms have to be implemented into the nanoparticle preparation procedure that allow for drug release profiles that match the requirements of the selected cargo molecule and its particular mode of action. Here, we describe two different methods to prepare crosslinked mucin nanoparticles that can release their cargo either on-demand or in a sustained manner. This method chapter includes a description of the preparation and characterization of mucin nanoparticles (stabilized either with synthetic DNA strands or with covalent crosslinks generated by free radical polymerization), as well as protocols to quantify the release of a model drug from those nanoparticles.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Davidson HJ, Kuonen VJ (2004) The tear film and ocular mucins. Vet Ophthalmol 7(2):71–77
Johansson ME, Sjövall H, Hansson GC (2013) The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 10(6):352–361
Lagow E, DeSouza MM, Carson DD (1999) Mammalian reproductive tract mucins. Hum Reprod Update 5(4):280–292
Bansil R, Turner BS (2006) Mucin structure, aggregation, physiological functions and biomedical applications. Curr Opin Colloid Interface Sci 11(2–3):164–170
Linden SK, Sutton P, Karlsson NG et al (2008) Mucins in the mucosal barrier to infection. Mucosal Immunol 1(3):183–197
McGuckin MA, Lindén SK, Sutton P et al (2011) Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9(4):265–278
Ma L, Gaisinskaya-Kipnis A, Kampf N et al (2015) Origins of hydration lubrication. Nat Commun 6:6060
Käsdorf BT, Weber F, Petrou G et al (2017) Mucin-inspired lubrication on hydrophobic surfaces. Biomacromolecules 18(8):2454–2462
Marczynski M, Jiang K, Blakeley M et al (2021) Structural alterations of mucins are associated with losses in functionality. Biomacromolecules 22(4):1600–1613
Lieleg O, Vladescu I, Ribbeck K (2010) Characterization of particle translocation through mucin hydrogels. Biophys J 98(9):1782–1789
Yakubov GE, McColl J, Bongaerts JH et al (2009) Viscous boundary lubrication of hydrophobic surfaces by mucin. Langmuir 25(4):2313–2321
Song J, Winkeljann B, Lieleg O (2019) The lubricity of mucin solutions is robust toward changes in physiological conditions. ACS Appl Bio Mater 2(8):3448–3457
Lieleg O, Lieleg C, Bloom J et al (2012) Mucin biopolymers as broad-spectrum antiviral agents. Biomacromolecules 13(6):1724–1732
Caldara M, Friedlander RS, Kavanaugh NL et al (2012) Mucin biopolymers prevent bacterial aggregation by retaining cells in the free-swimming state. Curr Biol 22(24):2325–2330
Rickert CA, Lutz TM, Marczynski M et al (2020) Several sterilization strategies maintain the functionality of mucin glycoproteins. Macromol Biosci 20(7):e2000090
Rickert CA, Bauer MG, Hoffmeister JC et al (2022) Effects of sterilization methods on the integrity and functionality of covalent mucin coatings on medical devices. Adv Mater Interfaces 9(3):2101716
Rickert CA, Wittmann B, Fromme R et al (2020) Highly transparent covalent mucin coatings improve the wettability and tribology of hydrophobic contact lenses. ACS Appl Mater Interfaces 12(25):28024–28033
Winkeljann B, Bauer MG, Marczynski M et al (2020) Covalent mucin coatings form stable anti-biofouling layers on a broad range of medical polymer materials. Adv Mater Interfaces 7(4):1902069
Song J, Lutz TM, Lang N et al (2021) Bioinspired dopamine/mucin coatings provide lubricity, wear protection, and cell-repellent properties for medical applications. Adv Healthc Mater 10(4):2000831
Duffy CV, David L, Crouzier T (2015) Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery. Acta Biomater 20:51–59
Kimna C, Winkeljann B, Song J et al (2020) Smart biopolymer-based multi-layers enable consecutive drug release events on demand. Adv Mater Interfaces 7(19):2000735
Marczynski M, Kimna C, Lieleg O (2021) Purified mucins in drug delivery research. Adv Drug Deliv Rev 178:113845
Yan H, Chircov C, Zhong X et al (2018) Reversible condensation of mucins into nanoparticles. Langmuir 34(45):13615–13625
Butnarasu C, Petrini P, Bracotti F et al (2022) Mucosomes: intrinsically mucoadhesive glycosylated mucin nanoparticles as multi-drug delivery platform. Adv Healthc Mater 11(15):e2200340
Lutz TM, Kimna C, Lieleg O (2022) A pH-stable, mucin based nanoparticle system for the co-delivery of hydrophobic and hydrophilic drugs. Int J Biol Macromol 215:102–112
Kimna C, Lutz TM, Yan H et al (2020) DNA strands trigger the intracellular release of drugs from mucin-based nanocarriers. ACS Nano 15(2):2350–2362
Fukui Y, Fukuda M, Fujimoto K (2018) Generation of mucin gel particles with self-degradable and-releasable properties. J Mater Chem B 6(5):781–788
Marczynski M, Rickert CA, Fuhrmann T et al (2022) An improved, filtration-based process to purify functional mucins from mucosal tissues with high yields. Sep Purif Technol 294:121209
Nowald C, Käsdorf B, Lieleg O (2017) Controlled nanoparticle release from a hydrogel by DNA-mediated particle disaggregation. J Control Release 246:71–78
Acknowledgements
This project was funded by the Federal Ministry of Education and Research (BMBF) and the Free State of Bavaria under the Excellence Strategy of the Federal Government and the Länder through the ONE MUNICH Project Munich Multiscale Biofabrication.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Kimna, C., Lutz, T.M., Lieleg, O. (2024). Fabrication and Characterization of Mucin Nanoparticles for Drug Delivery Applications. In: Kameyama, A. (eds) Mucins. Methods in Molecular Biology, vol 2763. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3670-1_33
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3670-1_33
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3669-5
Online ISBN: 978-1-0716-3670-1
eBook Packages: Springer Protocols