Adjustment of the cellular metabolism of pro-inflammatory macrophages is essential for their bactericidal function, however it underlies the development of many human diseases if induced chronically. Therefore, intervention of macrophage metabolic polarization has been recognized a potent strategy for their treatment. Although many small-molecule inhibitors affecting macrophage metabolism have been identified, their in vivo administration requires a tool for macrophage-specific delivery to limit their potential side effects. Glucan particles derived from yeast have been recently proposed as potential drug delivery carriers.

We demonstrated the potential of glucan particles for protein delivery in vivo, using the insect Drosophila melanogaster as a model organism. By employing genetic tools, we showed the capacity of yeast glucan particles to spread efficiently through the Drosophila body, to enter macrophages and to deliver an active transcription factor protein or small molecule metabolic inhibitor successfully. Systemic administration of glucan particles loaded with atorvastatin, the inhibitor of Hydroxy-methyl-glutaryl-CoA reductase (Hmgcr), leads to intervention of mevalonate pathway specifically in macrophages, without affecting HMGCR activity in other tissues. Using this tool, we demonstrate that mevalonate pathway is essential for macrophage pro-inflammatory polarization and individual’s survival of infection. Moreover, the glucan particles were nontoxic and induced only minimal immune response. The injection of glucan particles did not impair the ability of Drosophila to fight and survive infection by pathogenic bacteria.

From this study, Drosophila emerges as an excellent model to test and develop drug delivery systems based on glucan particles, specifically aimed to regulate macrophages.