title: Synthesis and characterization of an antibacterial hydrogel containing covalently bound vancomycin.
abstract: The release of freely loaded small molecules from biomaterials often exhibits an initial burst, inhibiting the ability of these materials to match drug release with the biomaterial's degradation period. In terms of antibiotic release systems, the remaining vehicle may become a substrate for colonization by bacterial biofilms once the payload is depleted, which can become life threatening. Secondary surgeries are typically performed to remove these empty depots as a means of preventing this type of infection. To maintain the effectiveness of a locally delivered antibiotic without the drawback of a second surgery, we propose a hydrogel drug delivery system in which the drug release rate of vancomycin and degradation rate of the hydrogel are linked via covalent incorporation of vancomycin in the hydrogel backbone. This was achieved through coupling PEG based monomer with vancomycin to create poly(β-amino ester) chemistry and verified through drug release and matrix degradation studies. Antibiotic release and material degradation were tunable via hydrophobic/hydrophilic content of the hydrogel matrix and extended up to 3 weeks in PBS sink conditions. Covalent addition of vancomycin to the hydrogel polymer backbone was verified through mass spectroscopy and HPLC peak addition, as well as radiotracing of collected HPLC fractions. Bioactivity of released vancomycin was also confirmed alongside the resulting antimicrobial activity of the reacted vancomycin releasate.
authors.affiliation: Department of Chemical and Materials Engineering and §Department of Biomedical Engineering, College of Engineering, University of Kentucky , Lexington, Kentucky 40506, United States.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lakes
authors.forename: Rebecca
authors.initials: R
authors.lastname: Peyyala
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ebersole
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
authors.forename: J Zach
authors.initials: JZ
authors.lastname: Hilt
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dziubla
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D011108:Polymers; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; C507253:poly(beta-amino ester); D014640:Vancomycin