Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery

[Display omitted] The sustained delivery of both hydrophobic and hydrophilic drugs from hydrogels has remained a challenge requiring the design and scalable production of complex multifunctional synthetic polymers. Here, we demonstrate that mucin glycoproteins, the gel-forming constituents of native...

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Bibliographic Details
Published in:Acta biomaterialia 2015-07, Vol.20, p.51-59
Main Authors: Duffy, Connor V., David, Laurent, Crouzier, Thomas
Format: Article
Language:English
Subjects:
Amphiphile
Animals
Bacteria
Biopolymers - chemistry
Cattle
Chemical Sciences
Covalence
Cross-Linking Reagents - chemistry
Crosslinking
Delayed-Action Preparations - pharmacology
Dextrans - chemistry
Drug delivery
Drug Delivery Systems
Drugs
Free radicals
HeLa Cells
Humans
Hydrogels
Hydrogels - chemistry
Hydrophobic and Hydrophilic Interactions
Material chemistry
Materials Testing
Methacrylates - chemistry
Methacrylation
Mucin hydrogel
Mucins - chemistry
Mucus
Paclitaxel - pharmacology
Polymers
Polymyxin B - pharmacology
Pronase - metabolism
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Summary:[Display omitted] The sustained delivery of both hydrophobic and hydrophilic drugs from hydrogels has remained a challenge requiring the design and scalable production of complex multifunctional synthetic polymers. Here, we demonstrate that mucin glycoproteins, the gel-forming constituents of native mucus, are suitable for assembly into robust hydrogels capable of facilitating the sustained release of hydrophobic and hydrophilic drugs. Covalently-crosslinked mucin hydrogels were generated via exposure of methacrylated mucin to ultraviolet light in the presence of a free radical photoinitiator. The hydrogels exhibited an elastic modulus similar to that of soft mammalian tissue and were sensitive to proteolytic degradation by pronase. Paclitaxel, a hydrophobic anti-cancer drug, and polymyxin B, a positively-charged hydrophilic antibacterial drug, were retained in the hydrogels and released linearly with time over seven days. After four weeks of drug release, the hydrogels continued to release sufficient amounts of active paclitaxel to reduce HeLa cell viability and sufficient amounts of active polymyxin B to prevent bacterial proliferation. Along with previously-established anti-inflammatory, anti-viral, and hydrocarbon-solubilizing properties of mucin, the results of this study establish mucin as a readily-available, chemically-versatile, naturally-biocompatible alternative to complex multifunctional synthetic polymers as building blocks in the design of biomaterials for sustained drug delivery.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2015.03.024