Drug delivery approaches for enhanced antibiofilm therapy

Biofilms have attracted increasing attention in recent years. Many bacterial infections are associated with biofilm formation. A bacterial biofilm is an aggregated membrane-like substance that is composed of a large number of bacteria and their secreted extracellular polymeric substances. The traditional antibiofilm approaches, such as chemotherapy based on antibiotics, are often ineffective in eradicating biofilms owing to the limited diffusion ability of antibiotics within biofilms and inactivation of antibiotics by biofilms. Moreover, a larger dosage of antibiotics could be effective, but leads to an increased tolerance. Smart drug delivery systems that deliver antibiotics into the biofilm interior is a promising strategy to meet this challenge. In this review, we focus on the methods to improve drug delivery efficiency for enhanced chemotherapy of biofilms. Furthermore, we have summarized chemical approaches for enhanced drug delivery, such as chemical shields, charge reversal, and dual corona enhanced delivery strategies; these methods focus on physicochemical biofilm properties and specific biofilm features. Afterwards, physical approaches are discussed, such as magnetism-mediated drug delivery, electricity-mediated drug delivery, ultrasound-mediated drug delivery, and shock wave-mediated drug delivery. Finally, a perspective on the development of next-generation antibiofilm drug delivery systems is given.