Therapy of infected wounds: overcoming clinical challenges by advanced drug delivery systems

In recent years, the incidence of infected wounds is steadily increasing, and so is the clinical as well as economic interest in effective therapies. These combine reduction of pathogen load in the wound with general wound management to facilitate the healing process. The success of current therapies is challenged by harsh conditions in the wound microenvironment, chronicity, and biofilm formation, thus impeding adequate concentrations of active antimicrobials at the site of infection. Inadequate dosing accuracy of systemically and topically applied antibiotics is prone to promote development of antibiotic resistance, while in the case of antiseptics, cytotoxicity is a major problem. Advanced drug delivery systems have the potential to enable the tailor-made application of antimicrobials to the side of action, resulting in an effective treatment with negligible side effects. This review provides a comprehensive overview of the current state of treatment options for the therapy of infected wounds. In this context, a special focus is set on delivery systems for antimicrobials ranging from semi-solid and liquid formulations over wound dressings to more advanced carriers such as nano-sized particulate systems, vesicular systems, electrospun fibers, and microneedles, which are discussed regarding their potential for effective therapy of wound infections. Further, established and novel models and analytical techniques for preclinical testing are introduced and a future perspective is provided.