Polymeric nano- and microparticulate drug delivery systems for treatment of biofilms

Abstract

Now-a-days healthcare systems face great challenges with antibiotic resistance and low efficacy of antibiotics when combating pathogenic bacteria and bacterial biofilms. Administration of an antibiotic in its free form is often ineffective due to lack of selectivity to the infectious site and breakdown of the antibiotic before it exerts its effect. Therefore, polymeric delivery systems, where the antibiotic is encapsulated into a formulation, have shown great promise, facilitating a high local drug concentration at the site of infection, a controlled drug release and less drug degradation. All this leads to improved therapeutic effects and fewer systemic side effects together with a lower risk of developing antibiotic resistance. Here, we review and provide a comprehensive overview of polymer-based nano- and microparticles as carriers for antimicrobial agents and their effect on eradicating bacterial biofilms. We have a main focus on polymeric particulates containing poly(lactic-co-glycolic acid), chitosan and polycaprolactone, but also strategies involving combinations of these polymers are included. Different production techniques are reviewed and important parameters for biofilm treatment are discussed such as drug loading capacity, control of drug release, influence of particle size and mobility in biofilms. Additionally, we reflect on other promising future strategies for combating biofilms such as lipid-polymer hybrid particles, enzymatic biofilm degradation, targeted/triggered antibiotic delivery and future alternatives to the conventional particles.

Keywords: Antibiotics; Antimicrobial tolerance; Antimicrobials; Bacterial biofilm infections; Chitosan; Microparticles; Nanoparticles; Poly(lactide-co-glycolide); Polycaprolactone.