Treating Polymicrobial Infections in Chronic Diabetic Wounds

Abstract

This review provides a comprehensive summary of issues associated with treating polyclonal bacterial biofilms in chronic diabetic wounds. We use this as a foundation and discuss the alternatives to conventional antibiotics and the emerging need for suitable drug delivery systems. In recent years, extraordinary advances have been made in the field of nanoparticle synthesis and packaging. However, these systems have not been incorporated into the clinic for treatments other than for cancer or severe genetic diseases. We present a unifying perspective on how the field is evolving and the need for an early amalgamation of engineering principles and a biological understanding of underlying phenomena in order to develop a therapy that is translatable to the clinic in a shorter time.

Keywords: biofilms; chronic diabetic wounds; drug delivery systems; engineering; nanoparticles; quorum sensing.

FIG 1

Biofilm formation and treatment options for chronic wounds. Planktonic bacteria secrete extracellular proteins and DNA and form a glycocalyx containing polysaccharide film around them, which marks the beginning of the formation of a biofilm. As the number of bacterial cells in the polysaccharide matrix increases due to cell division and from the environment, the matrix thickens and forms a mature biofilm. Each bacterial species proliferates in its own “territory” until nutrient and gas supplies are not limiting and secretes quorum-sensing molecules. Several classes of drug molecules exist for treating bacterial infections, but their efficacy is limited since they either cannot penetrate the matrix or are degraded by matrix components. Drug delivery systems have evolved to attenuate the problem.

FIG 2

IDR-1018 inhibits bacterial biofilm formation and eradicates preformed biofilms in Gram-negative and Gram-positive bacteria. Gram-positive and -negative bacterial biofilm formation was monitored for up to 3 days after treating the surface with IDR-1018 at sub-MICs. Biofilm eradication was evaluated 2 days after the flow cell surface came into contact with the bacteria. Bacterial presence was tested using live/dead staining using confocal microscopy. (Adapted from reference [published under a Creative Commons license].)

FIG 3

Various surface modifications of liposomes. Structure, composition, and surface modifications increase the utility of liposomes as drug carriers. A multilamellar (multiple lipid bilayer) liposome is more useful for controlled drug release. Surface modifications such as positive charge, PEGylation, and ligand conjugation are governed for the liposome to penetrate the biofilm better, protect it from degradation by proteases, and selectively bind to the target molecule, respectively.