Title : Nano-in-micro glucan particles for delivery of anti-TB drugs
Yeast derived β-glucan particles (GP) are 1–4 µm spherical, hollow and porous shells extracted from the cell wall of Saccharomyces cerevisiae (Baker’s yeast). Macrophage are the first line of defense against infections, as they phagocytose any bacilli or foreign particles they encounter. GP also act as pathogen associated molecular pattern (PAMPS) and the surface 1-3 β-glucan compositions of these particles facilitate receptor-mediated phagocytic cell uptake by immune cells bearing glucan receptors, such as macrophages and dendritic cells, thus making GP an ideal drug delivery vehicle to target phagocytic cells in the immune system. These also act as “natural polysaccharide immunomodulators,” and activate the immune system. These are non-toxic, biodegradable, biocompatible by nature and are generally regarded as safe (GRAS) approved by USFDA and EFSA.
We report here, the preparation of β-glucan particles (GP) from yeast cells, their characterization and demonstration of their rapid phagocytic uptake by the macrophage. The beta glucan structure of particles was validated by fourier transform infrared spectroscopy (FTIR), and NMR. The particles were loaded with an anti-tuberculosis drug, Rifabutin and sealed with alginate. Electron microscopy revealed the porous nature of these particles with drug nano-precipitates. The drug entrapment and drug loading was seen up to 81.46 ± 4.9 % and ~40.5 ± 1.9 %, respectively. These results indicate that these yeast derived glucan particles have the potential to be used as an effective agent for delivery of Rifabutin and targeting to macrophage.
Additionally, these particles have been seen to induce phagosomal maturation and autophagy induction within M.tb. infected macrophage. The particles thus not only act as effective delivery vehicles but also activate anti-microbial defence mechanism within host cells. Thus, the intracellular drug delivery supplements the innate response in M. tuberculosis infected macrophage, thereby accounting for the enhanced efficacy observed for this delivery system and holding promise for their use as formulations against TB.
Audience Take Away:
- The audience shall learn about the various applications of this delivery system.
- The audience shall learn about the preparation of these particles from yeast cells.
- The audience shall come to understand that these particles can be applied for the delivery of a diverse array of small molecules including prophylactics and therapeutics.
- The presentation shall explain the benefits of using this delivery system against intracellular infections, particularly M.tb.