Pharmaceutical Research 2015-01-01

Prevention of biofilm formation by methacrylate-based copolymer films loaded with rifampin, clarithromycin, doxycycline alone or in combination.

Warren E Rose, Daniel P Otto, Marique E Aucamp, Zach Miller, Melgardt M de Villiers

Index: Pharm. Res. 32(1) , 61-73, (2015)

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Abstract

This study reports the incorporation of the antibiotics rifampin, doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and their effect on biofilm prevention.Invasive procedures in patients such as surgical device, or intravenous or urinary catheter implantation, often results in complicated hospital-acquired nosocomial infections. Biofilm formation is essential to establish these infections on these devices and novel antibiotic delivery approaches are needed for more effective management.The films were evaluated in vitro for drug release and for their ability to prevent biofilm formation by methicillin susceptible and methicillin resistant Staphylococcus aureus. Surface tension components, obtained from contact angle measurements, and the morphology of the films evaluated by scanning electron microscopy were also investigated.In this study, antibiotic-loaded methacrylic copolymer films that effectively released rifampin, clarithromycin and doxycycline for up to 21 days prevented biofilm formation when tested in an in vitro bioreactor model. These drug loaded copolymer films provided the advantage by coating materials with a novel surface that was unsuitable for resettling of biofilms once the antibiotic was dissolved from the polymer surface. A combination of rifampin and clarithromycin released from the polymer film provided >99.9% kill of an MRSA inoculate for up to 72 h.Results showed that combining multiple drugs in copolymer films with unique surface properties, initial hydrophilicity and increase in roughness, can be an effective way to prevent biofilm formation.