Challenges and solutions in polymer drug delivery for bacterial biofilm treatment: A tissue-by-tissue account

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial communities (biofilms) are a particular concern in this context. Biofilms are responsible for most human infections and are inherently less susceptible to antibiotic treatments. Biofilms have been linked with several challenging chronic diseases, including implant-associated osteomyelitis and chronic wounds. The specific local environments present in the infected tissues further contribute to the rise in antibiotic resistance by limiting the efficacy of systemic antibiotic therapies and reducing drug concentrations at the infection site, which can lead to reoccurring infections. To overcome the shortcomings of systemic drug delivery, encapsulation within polymeric carriers has been shown to enhance antimicrobial efficacy, permeation and retention at the infection site. In this Review, we present an overview of current strategies for antimicrobial encapsulation within polymeric carriers, comparing challenges and solutions on a tissue-by-tissue basis. We compare challenges and proposed drug delivery solutions from the perspective of the local environments for biofilms found in oral, wound, gastric, urinary tract, bone, pulmonary, vaginal, ocular and middle/inner ear tissues. We will also discuss future challenges and barriers to clinical translation for these therapeutics. The following Review demonstrates there is a significant imbalance between the research focus being placed on different tissue types, with some targets (oral and wound biofims) being extensively more studied than others (vaginal and otitis media biofilms and endocarditis). Furthermore, the importance of the local tissue environment when selecting target therapies is demonstrated, with some materials being optimal choices for certain sites of bacterial infection, while having limited applicability in others.