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2014 MRS Fall Meeting


B11.01 - Crosslinked Mucin Hydrogels for Drug Delivery


Dec 3, 2014 9:45am ‐ Dec 3, 2014 10:00am

Description

The sustained delivery of both hydrophobic and hydrophilic drugs from hydrogels remains a challenge that requires the design of complex multifunctional synthetic polymers. In this work we exploit mucin glycoproteins, the gel-forming building blocks of natural mucus to deliver both hydrophobic and hydrophilic drugs. Mucins are a family of high molecular weight proteins which are densely glycosylated. Their central protein backbone contains hydrophobic and charged domains, while the mucin-associated glycans provide hydrogen bonding capabilities, high hydration, and negative charges. The biochemical versatility of mucins represents potential binding sites for certain drugs. If assembled into hydrogels, mucins could prevent drugs from freely diffusing out, leading to their sustained delivery. We generated methacrylated mucins which assembled into a covalently crosslinked mucin hydrogel when exposed to UV light. The rheological properties of the mucin gels were dominated by an elastic component, and the storage and loss moduli were maintained over four weeks when stored in buffer at 370C. We show that paclitaxel, a model hydrophobic anticancer drug and polymyxin B, a positively charged hydrophilic model antibiotic drug, are retained in the gel and release linearly over more than seven days. This was in contrast with the burst release of the negatively charged poly-glutamic acid and neutral dextran molecules. The activity of the released drugs was tested by measuring the decrease in viability of HeLa epithelial cell when exposed to paclitaxel and the killing of E. coli bacteria by polymyxin B. After three weeks of release, sufficient amounts of active paclitaxel were present to reduce HeLa cell viability. In addition, we show that the mucin gels can sequester polymyxin B and release it in sufficient amounts to inhibit bacteria growth over a month. This work shows that naturally occurring mucins have potential as a new building block for drug delivery biomaterials.

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