title: Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery.
abstract: 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.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 56-341C, Cambridge, MA 02139, USA.
authors.forename: Connor V
authors.initials: CV
authors.lastname: Duffy
authors.affiliation: Ingénierie des Matériaux Polymères, Université de Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5223, 15 Boulevard Latarjet, 69622 Villeurbanne Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: David
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 56-341C, Cambridge, MA 02139, USA; Ingénierie des Matériaux Polymères, Université de Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5223, 15 Boulevard Latarjet, 69622 Villeurbanne Cedex, France. Electronic address: thomas.crouzier@mit.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Crouzier
mesh_terms: D000818:Animals; D001704:Biopolymers / Q000737:chemistry*; D002417:Cattle; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry; D009077:Mucins / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011402:Pronase / Q000378:metabolism
chemical_list: D001704:Biopolymers; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003911:Dextrans; D020100:Hydrogels; D008689:Methacrylates; D009077:Mucins; C008384:methacrylic acid; D011402:Pronase; D011112:Polymyxin B; D017239:Paclitaxel
keywords: Amphiphile; Crosslinking; Drug delivery; Methacrylation; Mucin hydrogel