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.

Highly efficient delivery of potent anticancer iminoquinone derivative by multilayer hydrogel cubes

“…The slight increase of BA-TPQ release at 37 °C compared to that at 20 °C is attributed to a better solubility of the drug at the increased temperature. In contrast to the hydrophobic drug paclitaxel whose sustained release from mucin hydrogels reached 77 ± 5% after 7 days [70], the release of BA-TPQ in this work plateaued after three days and resulted in overall drug release of 14 ± 2% at pH = 7.4, 11 ± 3% at pH = 5, and 13 ± 3% at pH = 2. These results also demonstrate that the BA-TPQ release is independent of the environmental pH despite the pH-triggered size changes of the hydrogel cubes.…”

The particle in the spider's web: transport through biological hydrogels

“…193 Covalently crosslinked methacrylated bovine submaxillary mucin hydrogels also showed sustained release kinetics of both polymyxin B (a cationic antibiotic) and paclitaxel (a hydrophobic cancer drug). 194 …”

3D printing for drug manufacturing: A perspective on the future of pharmaceuticals

“…These factors include the size of the drug particles relative to the pore size of the hydrogel (if the drug is larger than the pores, diffusion is restricted, thereby reducing the burst release effect), the distribution of drug particles within the print (if the surface of the printed hydrogel contains a large concentration of the drug, a burst release is more likely), and whether the drug is loaded by mixing or bonding [58,73] . Herein lies another advantage of hydrogels over solid materials: drugs can be covalently or physically linked to the hydrogel network to limit the drug's release, whereas this is impossible in FDM [74,75] . Drug release would only occur as the bond between the drug and hydrogel, or the hydrogel itself, degrades.…”