Medical devices often serve as the starting point for bacterial

Transcription

Medical devices often serve as the starting point for bacterial
Medical devices often serve as the starting point for bacterial infections. The most frequently occurring
medical device-associated infections are urinary tract infections caused by indwelling catheters. Such
infections are further complicated by the ability of many pathogenic bacteria to form biofilm on polymer
surfaces thereby shielding the bacteria from conventional antibiotic treatment. In recent decades, several
commercial approaches have been pursued to prevent the initial bacterial colonization most of which rely on
surface coating of the biomedical device with antibiotics or antibacterial metals. However, due to the limited
clinical efficacy of these antibacterial materials new approaches are still needed.
This project is based on the overall hypothesis that by creating a material capable of sustained release of
antibiotics a better and more flexible solution to addressing the problem of bacterial colonization on
biomaterials can be achieved. In the present work, a commercially available silicone elastomer was modified
to allow for sustained release of antibiotics by impregnating it with a hydrogel-forming monomer, which was
subsequently polymerized while entrapped in the silicone material thereby forming a silicone-hydrogel
composite material. The material was investigated in terms of mechanical stability as well as the ability of
the embedded hydrogel to form a hydrophilic carrier matrix for drugs. The properties of the produced
material were extensively characterized through release of model compounds as well as by in-material
diffusion tracked by nuclear magnetic resonance imaging. The first-generation material was loaded with
ciprofloxacin and was found to inhibit bacterial growth on the material surface for a period of one month. A
second-generation copolymer material with improved mechanical properties was subsequently developed. It
was found to display slightly reduced release of ciprofloxacin, but was shown to release gentamicin and the
antimicrobial peptide colistin for a period of 15 days.
Overall, these results demonstrate that it is possible to create a silicone composite capable of releasing
drugs with very different properties. The physicochemical properties of the drug, e.g. the hydrophobicity, is
found to play a crucial role for increased drug loading and sustained release. This work represents the first
proof-of-concept in the rational development of a clinically relevant antibacterial material that in future can
be utilized for clinically used devices with extended resilience towards bacterial colonization.

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