A Topical Hydrogel With Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity [PublishAheadOfPrint]

Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. Whilst oral drug-delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection-site while reducing systemic side-effects.

This study determined the antibiofilm activity of a surgical wound-gel loaded with the iron-chelator deferiprone (Def) and the heme-analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. The activity against MDR Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of colony forming units and correlative light/electron microscopy.

While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gel (log10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for a significant activity against P.aeruginosa biofilms (log10 reduction of 1.3 for GaPP and 3.3 for Def-GaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds.

Def-GaPP delivered in a surgical wound-gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for a clinical utilization as therapy for topical biofilm-related infections.

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