Development of a poly(ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation

Ma, Hui; Darmawan, Erica T.; Zhang, Min; Zhang, Lei; Bryers, James D.

doi:10.1016/j.jconrel.2013.10.005

Cited by 49 publications

(36 citation statements)

References 44 publications

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“…We believe that the potent antibacterial and antibiofilm properties of gallium, combined with its good biocompatibility, make this iron-mimetic metal a suitable candidate for the coating of biomaterials and indwelling medical devices. In support of this possibility, a number of recent reports have highlighted the efficacy of galliumdoped materials in counteracting surface proliferation of some pathogenic bacteria, including A. baumannii (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 98%

Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium

Runci

Bonchi

Frangipani

et al. 2017

Antimicrob Agents Chemother

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Biofilm-associated infections caused by Acinetobacter baumannii are extremely recalcitrant to antibiotic treatment. We report that A. baumannii develops a mature biofilm when grown in complement-free human serum (HS). We demonstrate that 16 M gallium nitrate (GaN) drastically reduces A. baumannii growth and biofilm formation in HS, whereas 64 M GaN causes massive disruption of preformed A. baumannii biofilm. These findings pave the way to the repurposing of GaN as an antibiofilm agent for A. baumannii.

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Section: Discussionmentioning

confidence: 98%

Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium

Runci

Bonchi

Frangipani

et al. 2017

Antimicrob Agents Chemother

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“…While both compounds have been described previously as single treatments (19)(20)(21)(22) and in combination (18), the present study is the first to incorporate Def and GaPP in a clinically relevant hydrogel, thereby potentially serving as a novel antimicrobial strategy in the context of topical biofilm-related infections. The surgical hydrogel was used as a carrier to deliver Def and GaPP to biofilms, thereby complementing the gel's wound-healing properties with antimicrobial activity for topical treatment.…”

Section: Discussionmentioning

confidence: 98%

A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity

Richter

Thomas

Claeys

et al. 2017

Antimicrob Agents Chemother

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Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While 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. 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 CFU and correlative light/electron microscopy. While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gels (log 10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity against P. aeruginosa biofilms (log 10 reduction of 1.3 for GaPP and 3.3 for DefGaPP). 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 clinical utilization as a therapy for topical biofilm-related infections.KEYWORDS antimicrobial combinations, biofilms, drug delivery, iron metabolism M edical treatments for chronic infectious diseases are typically based on oral delivery of high-dose, long-term antibiotic therapies. Despite the risk for emerging antimicrobial resistance and the potential of side effects (e.g., gastrointestinal disorders, neutropenia, nephrotoxicity), there is a lack of suitable alternatives. Depending on the disease nature and localization, topical treatments can deliver high dosages of antimicrobials directly to an infection site while reducing unwanted systemic effects. Higher drug dosages are particularly needed to combat microbial biofilms (1). The ability of bacteria to form biofilms and establish resistance to antibiotics is a major biomedical threat, adding billions of dollars to health care costs worldwide (1-3). Biofilms are responsible for 80% of microbial infections in humans and are a common cause of chronic infections, including chronic wound and chronic sinus infections (4, 5), with increasing tolerance and subtle resistance mechanisms to antibiotic therapies (6-8).

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“…Current research is focused on developing methods to prevent or control biofilm formation (6,7). We recently found three analogues of N-acyl homoserine lactone that participate in quorum sensing, a system of bacterial cell-to-cell communication, and inhibit Porphyromonas gingivalis biofilm formation (8).…”

mentioning

confidence: 99%

Promotion of Endodontic Lesions in Rats by a Novel Extraradicular Biofilm Model Using Obturation Materials

Kuremoto

Noiri

Ishimoto

et al. 2014

Appl Environ Microbiol

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bAlthough extraradicular biofilm formation is related to refractory periapical periodontitis, the mechanism of extraradicular biofilm development, as well as its effect on periapical lesions, is unknown. Therefore, we aimed to develop an in vivo extraradicular biofilm model in rats and to identify and quantify extraradicular biofilm-forming bacteria while investigating the effect of extraradicular biofilms on periapical lesions. Periapical lesions were induced by exposing the pulpal tissue of the mandibular first molars of male Wistar rats to their oral environment. Four weeks later, gutta-percha points were excessively inserted into the mesial root canals of the right first molars (experimental sites) but not the left first molars (control sites). After 6 and 8 weeks of pulp exposure, the presence of extraradicular biofilms was confirmed histomorphologically, and biofilm-forming bacteria were identified by using classical culture methods. The biofilms were observed in the extraradicular area of the experimental sites. Similar species were detected both inside and outside the root canals. The bacterial count, quantified by real-time PCR assays, in the extraradicular area gradually increased in the experimental sites until 20 weeks after pulp exposure. After 8 weeks of pulp exposure, the periapical lesion volume that was measured by micro-computed tomography was significantly larger in the experimental sites than in the control sites (P < 0.05 by Welch's t test). These results suggest that we developed an extraradicular biofilm model in rats and that extraradicular biofilms affect developing periapical lesions. In clinical practice, we encounter patients in whom periapical periodontitis does not heal despite a root canal treatment following general dental procedures. The etiology is considered to be the result of residual bacteria in the lateral branch of the root canal, endodontic reinfection, or both. Recent studies have shown that biofilms that form outside the apical foramen, which are termed "extraradicular biofilm," are also involved in refractory periapical periodontitis (1-4). As the bacteria in biofilms are resistant to the host's immunoreaction and to antibiotics (5), dental biofilm diseases such as caries or periodontitis have been treated by mechanical removal. However, extraradicular biofilm is impossible to remove mechanically with nonsurgical endodontic treatments. As extraradicular biofilms cannot be accessed from the root canal for mechanical removal, the only treatment methods are endodontic surgery and tooth extraction.Current research is focused on developing methods to prevent or control biofilm formation (6, 7). We recently found three analogues of N-acyl homoserine lactone that participate in quorum sensing, a system of bacterial cell-to-cell communication, and inhibit Porphyromonas gingivalis biofilm formation (8). Furthermore, azithromycin, a 15-membered macrolide antibiotic, has an antibiofilm effect on P. gingivalis (9). For clinical applicability, these in vitro effects should be exami...

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Development of a poly(ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation

Cited by 49 publications

References 44 publications

Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium

Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium

A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity

Promotion of Endodontic Lesions in Rats by a Novel Extraradicular Biofilm Model Using Obturation Materials

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