Synthesis and Characterization of Charged Hydrogels for the Extended Delivery of Vancomycin

1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of Medicine, Mayo Clinic, 2Pharmacometrics Center, Duke Clinical Research Institute, 3Department of Laboratory Medicine and Pathology, Mayo Clinic, 4Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, 5Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, 6Department of Orthopedic Surgery, Mayo Graduate School, Mayo Clinic College of Medicine, Mayo Clinic
This article has been accepted and is currently in production

Abstract

Drug eluting polymers are of great interest due to their utility in cancer treatment, tissue regeneration, and infection prevention. It is desirable for these materials to offer tunable structural characteristics and molecular affinities, as well as excellent biocompatibility. In the context of surgery, infection of the wound site remains a significant risk for any procedure. It is standard practice to deliver systemic antimicrobial agents to combat infection of the surgical wound. To complement systemic therapy, an implantable, local delivery vehicle would be ideal. Our group investigated the utility of oligo(poly(ethylene glycol)fumarate) / sodium methacrylate (OPF/SMA) charged copolymers as a local delivery vehicle for the antimicrobial drug vancomycin. Here, we describe the methods of OPF synthesis, and OPF/SMA hydrogel production. Additionally, we demonstrate a facile chromatographic method for quantification of vancomycin loading and release from the OPF/SMA hydrogels. OPF-based biopolymers have proven to be biocompatible in vivo and have wide-ranging applications due to their ability to be crosslinked chemically or via ultra-violet irradiation. OPF is readily functionalized with charged groups, or mixed with other polymers to create co-polymers with optimal structural properties or unique responses to environmental stimuli. This study utilizes an array of charged OPF/SMA co-polymers to develop a controlled release vehicle for the broad spectrum antibiotic vancomycin based upon charge-charge interactions. Hydrogel loading of vancomycin can be quantified with a simple high performance liquid chromatography method. Vancomycin release from the hydrogels is initiated in the presence of free ions in solution, and release is buffered by free charges on the pendant chains within the crosslinked hydrogel. In sum, we report an efficient method for synthesis and characterization of the OPF/SMA hydrogels, and quantification of their ability to load and release vancomycin.