New Anti-Infective Coatings of Medical Implants

Abstract

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.A major risk associated with surgical placement of medical implants such as endoprostheses or vascular prostheses is their high infection rate (4,8). This is not only of prime importance for the patient but also imposes a high financial cost on the economy (21). Synthetic vascular grafts such as polytetrafluoroethylene (PTFE) prostheses are easily accessible to pathogens, mostly Staphylococcus aureus and Staphylococcus epidermidis. These pathogens colonize the implant by adhering to the patient's own proteins located on the surface of the graft and form a biofilm (1,14,16,23,34). The formation of biofilms on biomaterials presents challenging complications in the field of medical implants (2,12,24,28,30). In a biofilm, bacteria are well protected from the host immune defense. An increase in antibiotic resistance is the consequence (6,8,35); even high local concentrations of antibiotics do not completely eradicate bacteria in biofilms (8, 10). It is therefore of great importance to prevent bacterial adhesion on vascular grafts (7). This can be achieved by antibiotic surface coatings.There have been several approaches to equipping vascular grafts with anti-infective agents to prevent bacterial colonization. Different antim...

Drug Eluting Stents Coated With Rapamycin Crystals for the Prevention of Restenosis and Biofilm Formation

“…When the rate of degradation was high, then the release concentration was also found out to be high. Similar condition was experienced by Matl et al 29 during their research when they analysed the release of gentamicin and teicoplanin from PTFE vascular stents grafted with carriers like DL-lactic acid, tocopherol acetate and dynasan. Zarida et al 30 reported that the rate of release of tobramycin and gentamicin was due to the rate of degradation of the drug containing calcium phosphate beads.…”

Abstracts „Bayern Innovativ'

“…uncemented coated titanium disc: Gentamicinpalmitat und zahlreiche andere Antibiotika-/Antiseptikaverbindungen mit Fettsäuren wurden zwischenzeitlich mit Erfolg zur bakteriziden Ausrüstung von Implantaten wie zementloser Endoprothesen, Wirbelkörper, Zahnimplantate, Gefäßprothesen, Nahtmaterial und Knochenersatzstoffe eingesetzt [9], [7], [4], [5], [3] . In enger Kooperation von Universität und Industrie werden derzeit die Grundlagen für die humane Anwendung erarbeitet.…”

“…Es kommt vielmehr bei den Mikro-organismen durch Quorum-Sensing zu einer Stoffwechsel-umstellung. Die Mikroorganismen wachsen nicht mehr in einer planktonischen sondern in einer sessilen Form [1,4,7], Die MHK der Bakterien in mg/1 ist dann gegenüber Antibiotika im Vergleich zum planktonischen Wachstum um das bis zu lOOOfache höher [9], Um die Biofilmbildung zu verhindern, muss daher das Anheften von Mikroorganismen an die Fremdkörper verhindert werden. Bei der systemischen intravenösen Antibiotikaprophylaxe bzw.…”

Antimicrobial Biomimetics

“…Recently, new lipid-based formulations to incorporate antibiotics for anti-infective action in grafts were developed. In this case, PFTE grafts were coated with lipophilic agents such as poly-lactid acid or tocopherol acetate as carriers for gentamicin and teicoplanin, in order to release high drug concentrations locally and completely inhibit bacterial colonization on the implant (Matl et al, 2008). A recent study also reported the covalent attachment of quaternary ammonium groups to stainless steel and porous filter paper (cellulose) surfaces, through low-pressure plasma-enhanced functionalization (Jampala et al, 2008).…”