title: Keratin hydrogels support the sustained release of bioactive ciprofloxacin.
abstract: Keratins are naturally derived proteins that can be fabricated into several biomaterial forms including hydrogels. These materials are a potential polymeric system for several tissue engineering and regenerative medicine applications due to their ability to support cell attachment, proliferation, and migration. However, little is known regarding their ability to support sustained release of therapeutic agents. This report describes the use of keratin hydrogels for sustained release of the antibiotic ciprofloxacin, which may prove useful to traumatic injury applications that would benefit from materials promoting tissue regeneration while also preventing acute infection. Hydrogels were formed from keratins obtained by oxidative extraction and known as keratose. We found that keratose hydrogels released ~60% of loaded ciprofloxacin over the first 10 days and that continued release was detectable over the course of 3 weeks. Released ciprofloxacin was bioactive, inhibiting growth of Staphylococcus aureus for 23 days in vitro and for 2 weeks in a mouse subcutaneous model. The rate of ciprofloxacin release was highly correlated with degradation of the keratin hydrogel and not consistent with simple diffusion. Further experiments indicated that ciprofloxacin binds to keratose through electrostatic interactions. These studies demonstrate the specific use of keratose hydrogels for the release of antibiotic and the potential for the more general use of this material in tissue engineering and regenerative medicine applications.
authors.affiliation: Department of Biomedical Engineering, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA. jsaul@wfubmc.edu
authors.forename: Justin M
authors.initials: JM
authors.lastname: Saul
authors.forename: Mary D
authors.initials: MD
authors.lastname: Ellenburg
authors.forename: Roche C
authors.initials: RC
authors.lastname: de Guzman
authors.forename: Mark
authors.initials: M
authors.lastname: Van Dyke
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002939:Ciprofloxacin / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism*; D007633:Keratins / Q000737:chemistry* / Q000378:metabolism*; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D012756:Sheep
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D002939:Ciprofloxacin; D007633:Keratins