title: Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.
abstract: Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA. johnna.temenoff@bme.gatech.edu.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Peng
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA. johnna.temenoff@bme.gatech.edu.
authors.forename: Liane E
authors.initials: LE
authors.lastname: Tellier
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA. johnna.temenoff@bme.gatech.edu and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332, USA.
authors.forename: Johnna S
authors.initials: JS
authors.lastname: Temenoff
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D006493:Heparin / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D013455:Sulfur / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D013455:Sulfur; D006493:Heparin