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Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation
Journal article   Open access

Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation

Zhiling Zhang, Camilla A Nix, Utku K Ercan, Jonathan A Gerstenhaber, Suresh G Joshi and Yinghui Zhong
PloS one, v 9(1), pp e84360-e84360
2014
PMID: 24409292
url
https://doi.org/10.1371/journal.pone.0084360View
Published, Version of Record (VoR) Open

Abstract

Prostheses and Implants - adverse effects Calcium - metabolism Infection - drug therapy Humans Inflammation - etiology Infection - etiology Drug Delivery Systems Minocycline - pharmacokinetics Inflammation - drug therapy Anti-Bacterial Agents - pharmacokinetics Hydrophobic and Hydrophilic Interactions Minocycline - administration & dosage Anti-Bacterial Agents - administration & dosage
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.

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Web of Science research areas
Biochemistry & Molecular Biology
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