Controlled drug delivery systems in eradicating bacterial biofilm-associated infections

Drug delivery systems (DDS) have extensively progressed over the past decades for eradicating the bacteria embedded in biofilms while minimizing the side effects of antimicrobials on the normal tissues. They possess potential in solving the challenges of intrinsic antimicrobial-resistance and poor penetration of antimicrobials into biofilms. However, the guidelines for developing a controlled DDS for combating bacterial biofilms are limited. In this review, classical mechanisms and mathematical models of DDS were summarized in order to lay the foundation of controlled DDS development. Strategies for building controlled DDS were proposed based on the process of biofilm formation, including surface coatings, fibers, nanoparticles as DDS to prevent biofilm formation and eradicate bacterial biofilm-associated infections. The challenges that still remain in DDS design were discussed and future directions were suggested. We hope this review could give a "road map" to inspire readers and boost the development of the new generation of controlled drug release system for antimicrobial applications.