title: Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation.
abstract: Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca(2+) is less stable at acidic pH, enabling 'smart' drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca(2+) concentration, and Ca(2+) incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca(2+) binding affinity, enabling its use in a variety of biomedical applications.
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Camilla A
authors.initials: CA
authors.lastname: Nix
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Utku K
authors.initials: UK
authors.lastname: Ercan
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Gerstenhaber
authors.affiliation: Surgical Infection Program, Department of Surgery and Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Suresh G
authors.initials: SG
authors.lastname: Joshi
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007239:Infections / Q000188:drug therapy / Q000209:etiology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008911:Minocycline / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019736:Prostheses and Implants / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline; D002118:Calcium