Activation of Macrophages: Establishing a Role for Polysaccharides in Drug Delivery Strategies Envisaging Antibacterial Therapy

Infectious diseases are an important health concern, as several pathogens have developed the ability to survive inside phagocytic cells (mostly macrophages), encountered at early infection stages, using these cells as trojan horses. In fact, in several cases macrophages have become a nutrient reservoir that helps pathogens to grow in number and spread. It is frequent that conventional therapeutic schedules include long periods of drug intake, at high doses, in some cases leading to severe side effects and clinical relapses due to prolonged intake, along with an increased risk for the development of antibiotic resistances. Therefore, there is a compelling need to develop new therapeutic strategies providing a targeted drug delivery to macrophages. These cells have unique surface receptors that might recognise preferentially several polysaccharide moieties present on the surface of infecting organisms, including in the bacterial cell wall. Benefiting from a similar composition regarding the referred moieties, polysaccharides might be good candidates to compose the matrix of drug carriers aimed at macrophage targeting, as they can use the same recognition pathways of the infecting organisms. This review describes the features and the role of macrophages in infectious conditions, while addressing their potential as therapeutic targets and unravelling the prominent role of polysaccharides as matrix materials of drug delivery systems developed for the therapy of infectious diseases. Keywords: Bacterial infections, drug delivery, macrophage activation, macrophage receptors, phagocytosis, polysaccharides.