Stimulus-Responsive Antibiotic Releasing Systems for the Treatment of Wound Infections

ACS Appl Bio Mater. 2019 Feb 18;2(2):704-716. doi: 10.1021/acsabm.8b00577. Epub 2019 Jan 18.

Abstract

There remains an unmet need for innovative treatments for chronic wound infections as they continue to be a financial and social burden on society. Because of the dynamic nature of wounds, this study investigated the utilization of stimulus-responsive plasma polymers for the development of pH- and thermoresponsive antibiotic delivery systems for the treatment of wound infections. Porous silicon films were loaded with the antibiotic levofloxacin (LVX) and subsequently coated with plasma polymer layers: first, poly(1,7-octadiene) (pOCT) for stability, followed by either the temperature-responsive polymer poly N,N-diethylacrylamide (pDEA) or the pH- responsive polymer poly 2-(diethylamino)ethyl methacrylate (pDEAEMA), to fabricate two delivery systems. The delivery systems were thoroughly characterized chemically and physically and tested in vitro through drug release and bacterial zone of inhibition studies. After a 16 h time point, the system containing pDEA achieved 3.2-fold greater release at 45 °C compared to 22 °C, whereas the system containing pDEAEMA achieved a 2.2-fold greater release when exposed to pH 8.5 media compared to pH 6.2 media. Furthermore, both systems retained their antimicrobial activity and demonstrated stimulus-responsive release to form zones of inhibition on relevant wound pathogens, Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus aureus. Therefore, this proof-of-principle study confirms that stimulus-responsive porous silicon films can be utilized to deliver antibiotic when exposed to physiologically relevant stimuli such as pH and temperature with the potential to be applied to other pharmaceutics.

Keywords: antibiotics; drug delivery systems; levofloxacin; porous silicon; stimulus-responsive polymers; wound infections.