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Antimicrobial Agents and Chemotherapy, June 2008, p. 1957-1963, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.01438-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

New Anti-Infective Coatings of Medical Implants

Institute of Medical Engineering, Technische Universität München, Garching,¹ Institut für Experimentelle Onkologie und Therapieforschung, Klinikum r. d. Isar,² Department of Pharmacy-Pharmaceutical Technology, Ludwig-Maximilians-Universität München, Munich, Germany³

Received 6 November 2007/ Returned for modification 11 December 2007/ Accepted 28 February 2008

Implantable devices are highly susceptible to infection and are therefore a major risk in surgery. The present work presents a novel strategy to prevent the formation of a biofilm on polytetrafluoroethylene (PTFE) grafts. PTFE grafts were coated with gentamicin and teicoplanin incorporated into different lipid-like carriers under aseptic conditions in a dipping process. Poly-D,L-lactic acid, tocopherol acetate, the diglyceride Softisan 649, and the triglyceride Dynasan 118 were used as drug carriers. The drug release kinetics, anti-infective characteristics, biocompatibility, and hemocompatibility of the coatings developed were studied. All coatings showed an initial drug burst, followed by a low continuous drug release over 96 h. The dimension of release kinetics depended on the carrier used. All coated prostheses reduced bacterial growth drastically over 24 h, even below pathologically relevant concentrations. Different cytotoxic levels could be observed, revealing tocopherol acetate as the most promising biocompatible carrier. A possible reason for the highly cytotoxic effect of Softisan 649 could be assessed by demonstrating incorporated lipids in the cell soma with Oil Red O staining. Tromboelastography studies, enzyme-linked immunosorbent assays, and an amidolytic substrate assay could confirm the hemocompatibility of individual coatings. The development of the biodegradable drug delivery systems described here and in vitro studies of those systems highlight the most important requirements for effective as well as compatible anti-infective coatings of PTFE grafts. Through continuous local release, high drug levels can be produced at only the targeted area and physiological bacterial proliferation can be completely inhibited, while biocompatibility as well as hemocompatibility can be ensured.

Published ahead of print on 24 March 2008.