1,721,063 research outputs found
Novel strategies to prevent and control biofilm growth on central venous catheters
No full textIn last decades, several strategies based on antiadhesive, antiseptic or antibiotic coating of polymers have been developed to prevent biofilm formation on the outer and inner surfaces of medical devices. However, the so far developed medicated devices are able to delay microbial colonization in spite of definitively solving the problem of biofilm formation and related infections. In fact, these devices mainly suffer from a relatively short persistence of antimicrobial action as consequence of an early and rapid drug release.
In the last years, we focused our research efforts in developing different experimental approaches to prevent microbial colonization of central venous catheters based on the adsorption of antimicrobial agents to synthesized and properly functionalized polyurethanes with the aim to control drug adsorption and release.
The new antibiofilm strategies we are dealing with concern: i) the development of antimicrobial polymers by the use of polyurethanes able to coordinate metal ions (Ag+, Zn2+, etc); ii) the exploiting of the biofilm matrix-degrading enzyme, DispersinB, to enhance the penetration of antibiotics through the biofilm; iii) the set up of a magnetic nanoparticles (MNPs)-based targeting system to fight in situ catheter-related infections.
As the metal ion-containing polymers are concerned, a carboxylated polyetherurethane (PEUA) was treated with silver, copper, zinc, aluminium and iron salts, thus obtaining PEUA-Ag, PEUA-Cu, PEUA-Zn, PEUA-Al and PEUA-Fe. A part from PEUA-Al, all polymers showed significant antimicrobial properties. The most active was PEUA-Ag which resulted to be able to inhibit S. epidermidis biofilm formation up to 16 days.
As the Dispersin B is concerned, we carried out collaborative experiments with Jeff Kaplan group to evaluate the antibiofilm activity of this β-N-acetylglucosaminidase once adsorbed to our polyurethanes, either alone or in combination with antibiotics.
Finally, we are currently developing a strategy to fight in situ biofilm development by the use of antibiotic loaded-MNPs to be intravenously injected in at risk patients and driven to the device implantation areas by the application of an external magnetic field. This approach will allow an in situ, on demand treatment of biofilm infections. Drugs are expected be released only in the close surroundings of the colonized device and when clinically required. If the planned experiments in animals will be successful, patients could be treated either immediately after the device implant or later in presence of signs of infection
NOVEL STRATEGIES TO CONTROL BIOFILM FORMATION ON MEDICAL DEVICES.
No full textDevice coating with antimicrobial agents able to inhibit microbial colonisation and biofilm formation represents a pivotal approach in the prevention of medical device-associated infections. Existing antiseptic or antibiotic loaded devices mainly suffer from a relatively short persistence of antimicrobial action as consequence of an early and rapid drug release. On the other hand, the most frequently implicated bugs in device colonisation, such as Staphylococcus, Pseudomonas and Candida spp, are known to develop a largely increased antibiotic resistance due to their sessile mode of growth to form a biofilm. These issues are both critical for the management of patients in clinical settings and need the development of innovative and safer medical devices refractory to microbial adhesion and biofilm formation.
To this aim, we designed and tested in vitro experimental models based on the adsorption on functionalised polymers of: i) a water-insoluble antibiotic active at device level and not used for systemic therapy; ii) pore-former molecules able to modulate drug loading and release; iii) transition metal ions able to synergistically act together with antibiotics.
In particular, we developed new drug-releasing polyurethanes loaded with: i) usnic acid as a water-insoluble drug able to exert antibiofilm activity against Gram-positives and to interfere with quorum-sensing phenomena in Gram-negatives; ii) albumin and polyethylene glycol as porogens promoting the release of rifampin, cefamandole nafate and fluconazole from polyurethanes; iii) silver ions and ciprofloxacin exhibiting a long-lasting antibacterial synergistic activity against Gram-positives and Gram-negatives.
Combined entrapping within our functionalised polyurethanes of antibiotic/antifungal drugs and transition metal ions, when needed in conjunction with porogens as drug release modulators, seem to offer promising strategies both in prevention of bacterial colonisation and biofilm formation and control of drug resistance
Rilascio di una combinazione di antibiotici da matrici poliuretaniche per prevenire la formazione di biofilm microbici e contrastare l’insorgenza di antibiotico-resistenza.
No full textUna combinazione di antibiotici è stata adsorbita su matrici poliuretaniche per contrastare la formazione di biofilm microbici che sono gli agenti causanti le infezioni correlate a dispositivi medici. Lo scopo del lavoro è stato quello di studiare la cinetica di rilascio dei farmaci come pure di valutare l'attività antibatterica nel tempo del sistema sviluppato. Gli antibiotici scelti per l'adsorbimento possedevano meccanismi di azione diversi al fine di controllare lo sviluppo dell'insorgenza di microrganismi antibiotico-resistenti
Poliuretani funzionalizzati a rilascio combinato di rifampicina/cefamandolo e polietilenglicole in grado di prevenire la colonizzazione batterica e l’insorgenza di antibiotico-resistenza.
No full textI poliuretani rappresentano come noto i materiali polimerici più diffusamente impiegati per la realizzazione di dispositivi medici impiantabili, in particolare di cateteri venosi centrali.
Il loro ampio utilizzo è essenzialmente dovuto alla loro elevata biocompatibilità ed alle loro caratteristiche chimico-fisiche che li rendono idonei a diverse applicazioni.
Una complicazione associata all'impianto di dispositivi medici è lo sviluppo di infezioni, dovute alla colonizzazione del dispositivo medico da parte di microrganismi. Per contrastare la colonizzazione microbica, due antibiotici sono stati intrappolati in matrici poliuretaniche in presenza di agenti formanti pori (albumina e polietilenglicole). I buoni risultati di attività antimicrobica otttenuti in quetso studio indicano come l'approccio sperimentale adottato possa contribuire alla prevenzione della colonizzazione microbica di dispositivi medici e al controllo dell’insorgenza di resistenza batterica
Biomateriali a rilascio di agenti antimicrobici per lo sviluppo di dispositivi medici anti-biofilm.
No full textI notevoli progressi in campo medico concretizzati negli ultimi decenni sono in parte da attribuire al crescente sviluppo di nuovi materiali sintetici, idonei per la realizzazione di dispositivi medici impiantabili. Al loro impiego è, tuttavia, associata una grave complicanza clinica: l’instaurarsi di processi infettivi. Tra le diverse specie microbiche responsabili, le più comuni sono batteri gram positivi (stafilococchi), e lieviti (candide).
Al fine di sviluppare biomateriali polimerici capaci di inibire la colonizzazione da specie microbica e la conseguente formazione di biofilm sono state messe appunto diverse strategie.
L’adsorbimento sulle matrici polimeriche di una o più specie antimicrobiche (cefamandole nafate, rifampicina, amoxicillina e vancomicina) o di specie antifungine (fluconazolo) è stato uno degli approcci di maggior successo, da noi perseguiti.
Metodo alternativo è stato, invece, la modifica superficiale della matrice polimerica stessa, mediante salificazione di gruppi funzionali specifici con metalli pesanti dalle note proprietà antibatteriche, come l’Ag. Il successivo adsorbimento sulla matrice così modificata, dell’antibiotico ciprofloxacina, ha permesso di ottenere un biomateriale antibiofilm la cui attività non è limitata dal potenziale sviluppo di antibiotico resistenza
Poliuretani a rilascio di fluconazolo in grado di prevenire la colonizzazione da Candida albicans nei dispositivi medici impiantabili
No full textIl 90% delle batteriemie ospedaliere è correlato all’uso di dispositivi medici impiantabili. Tali infezioni sono associate ad una aumentata mortalità, oltre che ad una crescita dei costi sanitari conseguente al prolungamento del tempo di ospedalizzazione. Nonostante la gravità e la crescente incidenza delle infezioni fungine associate a dispositivi medici impiantabili, pochi studi sono stati finora indirizzati alla loro prevenzione, probabilmente perchè la capacità di formare biofilm da parte di specie fungine è stata descritta solo recentemente. Allo scopo di realizzare polimeri capaci di inibire la colonizzazione da Candida albicans, abbiamo adsorbito fluconazolo a poliuretani funzionalizzati. Il migliore modello sperimentale è risultato essere quello costituito da un polimero idrofobico con intrappolato il 25% in peso di fluconazolo e albumina come agente porogeno. Tale sistema inibiva per otto giorni sia la crescita di Candida albicans che la formazione di biofilm
Synthesis, characterization, and in vitro activity of antibiotic releasing polyurethanes to prevent bacterial resistance
No full textCentral venous catheters are a major cause of nosocomial bloodstream infections. Different attempts have been made to incorporate antimicrobial agents into catheters, particularly directed at the surface-coating of devices. To facilitate the antimicrobial adsorption, various cationic surfactants, which however showed several problems, have been used. On the other hand, impregnated catheters with only antimicrobials have demonstrated a short-term duration due to the difficulties to deliver the drug slowly. Thus, in order to obtain high antimicrobial-polymer affinity we synthesized or modified polyurethanes to introduce different functional groups. Polymers were loaded with two antibiotics, cefamandole nafate and rifampin (RIF), chosen for boththeir functional groups and their action spectrum. The in vitro release behavior showed that the elution of drugs depended on the matrix hydrophilicity and on the antibiotic–polymer and antibiotic–antibiotic interactions. To increase the amount of drug released, polyethylene glycol (PEG) used as a pore forming agent at different molecular weights was incorporated in the polymer bulk with antibiotics. As for the in vitro antimicrobial activity of matrices, assessed by Kirby-Bauer test, it was seen that antibiotics released from various formulations inhibited the bacterial growth and exerted a synergistic effect when both were present. In particular, PEG10000-containing polymer was active against the RIF-resistant S. aureus strain up to 23 days. These results suggest that the combined entrapping of antibiotics and pore formers in these novel polymer systems could be promising to prevent the bacterial colonization and to control the emergence of bacterial resistance
Inhibition of Candida growth and biofilm formation on polyurethanes by fluconazole adsorption.
No full textRecent attempts to prevent device-related infections included several strategies among which catheter coating with antibiotics resulted to be one of the most promising. However, so far only sporadic studies were designed to prevent fungal colonization of devices presumably because of the only recently described ability of Candida species to form biofilms. In this study we report in vitro experiments on the efficacy of coating of newly synthesized polyurethanes with the antifungal drug fluconazole in preventing polymer colonization and biofilm formation by Candida albicans.
Polymers used in this study are three synthesized urethane polymers having different functional groups in the side-chain: hydroxyl groups, primary amino groups and tertiary amino groups. Fluconazole was adsorbed on round shaped disks made of the above described polyurethanes. The kinetics of fluconazole release from polymers, either containing or not albumin as pore forming agent, was studied by keeping fluconazole-loaded polymeric disks in water for increasing times up to 8 days. The antifungal activity of polymers was studied by the Kirby Bauer test and scanning electron microscopy.
Among the tested polymers, the most hydrophilic ones were able to adsorb higher drug amounts by establishing “hydrogen bond” and “van der Waals” interactions. The kinetics of fluconazole release from polymers was influenced by the degree of polymer swelling in water and resulted significantly improved by the albumin incorporation in polyurethanes which increased polymer porosity. In our best experimental in vitro model consisting of an hydrophilic polymeric disk (average weight 250 mg) impregnated with 62.5mg albumin and 62.5mg fluconazole, the Candida albicans growth was inhibited as evidenced by the Kirby Bauer test and biofilm formation on polymeric surface was not observed up to 8 days as evidenced by scanning electron microscopy.
Overall, data obtained from our newly synthesized functionalized polyurethanes loaded with fluconazole seem to be very promising in the perspective to develop medical devices refractory to Candida colonization
- …
