TY - JOUR
T1 - Mucus-Mimicking Mucin-Based Hydrogels by Tandem Chemical and Physical Crosslinking
AU - Porfiryeva, Natalia N.
AU - Zlotver, Ivan
AU - Davidovich-Pinhas, Maya
AU - Sosnik, Alejandro
N1 - Publisher Copyright:
© 2024 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.
PY - 2024/7
Y1 - 2024/7
N2 - Mucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulates the moisture levels of the tissue and is capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal membranes to assess mucoadhesion and muco-penetration of pharmaceutical formulations which may struggle with limited accessibility, reproducibility, and ethical questions. Aiming to develop a platform for the rationale study of the interaction of drugs and delivery systems with mucosal tissues, in this work mucus-mimicking mucin-based hydrogels are synthesized by the tandem chemical and physical crosslinking of mucin aqueous solutions. Chemical crosslinking is achieved with glutaraldehyde (0.3% and 0.75% w/v), while physical crosslinking by one or two freeze-thawing cycles. Hydrogels after one freeze-thawing cycle show water content of 97.6–98.1%, density of 0.0529-0.0648 g cm⁻3, and storage and loss moduli of ≈40–60 and ≈3–5 Pa, respectively, that resemble the properties of native gastrointestinal mucus. The mechanical stability of the hydrogels increases over the number of freeze-thawing cycles. Overall results highlight the potential of this simple, reproducible, and scalable method to produce artificial mucus-mimicking hydrogels for different applications in pharmaceutical research.
AB - Mucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulates the moisture levels of the tissue and is capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal membranes to assess mucoadhesion and muco-penetration of pharmaceutical formulations which may struggle with limited accessibility, reproducibility, and ethical questions. Aiming to develop a platform for the rationale study of the interaction of drugs and delivery systems with mucosal tissues, in this work mucus-mimicking mucin-based hydrogels are synthesized by the tandem chemical and physical crosslinking of mucin aqueous solutions. Chemical crosslinking is achieved with glutaraldehyde (0.3% and 0.75% w/v), while physical crosslinking by one or two freeze-thawing cycles. Hydrogels after one freeze-thawing cycle show water content of 97.6–98.1%, density of 0.0529-0.0648 g cm⁻3, and storage and loss moduli of ≈40–60 and ≈3–5 Pa, respectively, that resemble the properties of native gastrointestinal mucus. The mechanical stability of the hydrogels increases over the number of freeze-thawing cycles. Overall results highlight the potential of this simple, reproducible, and scalable method to produce artificial mucus-mimicking hydrogels for different applications in pharmaceutical research.
KW - mucin hydrogels
KW - mucosal tissues
KW - mucus-mimicking hydrogels
KW - tandem chemical-physical crosslinking
UR - http://www.scopus.com/inward/record.url?scp=85188823833&partnerID=8YFLogxK
U2 - 10.1002/mabi.202400028
DO - 10.1002/mabi.202400028
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C2 - 38511568
AN - SCOPUS:85188823833
SN - 1616-5187
VL - 24
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 7
M1 - 2400028
ER -