Approximately half of all nosocomial
bloodstream infections are caused by bacterial colonization of
vascular catheters. Attempts have been made to improve devices using anti-adhesive or antimicrobial coatings; however, it is often difficult to bind coatings stably to
catheter materials, and the low amounts of
drug in thin-film coatings limit effective long-term release. Interpenetrating
polymer networks (IPNs) are
polymer hybrid materials with unique drug release properties. While IPNs have been extensively investigated for use in
tablet- or
capsule-based drug delivery systems, the potential for use of IPNs in drug release medical devices remains largely unexplored. Here, we investigated the use of
silicone-
hydrogel IPNs as a
catheter material to provide slow anti-bacterial drug-release functionality. IPN
catheters were produced by the sequential method, using supercritical CO2 as a
solvent to polymerize and crosslink poly(2-hydroxyethyl methacrylate) (
PHEMA) in
silicone elastomer. The design was tested against Staphylococcus aureus colonization after loading with
dicloxacillin (DCX) alone or in combination with
thioridazine (TDZ), the latter of which is known to synergistically potentiate the antibacterial effect of DCX against both
methicillin-sensitive and methicillin-resistant S. aureus. The hydrophilic
PHEMA component allowed for
drug loading in the
catheters by passive diffusion and provided controlled release properties. The
drug-loaded IPN material inhibited bacterial growth on
agar plates for up to two weeks and in blood cultures for up to five days, and it withstood 24h of seeding with resilient biofilm aggregates. The combined loading of DCX+TDZ enhanced the antibacterial efficiency in static in vitro experiments, although release analyses revealed that this effect was due to an enhanced loading capacity of DCX when co-loaded with TDZ. Lastly, the IPN
catheters were tested in a novel porcine model of
central venous catheter-related
infection, in which
drug-loaded IPN
catheters were found to significantly decrease the frequency of
infection.