9th International Drug Chemistry Congress, Antalya, Turkey, 8 - 11 April 2021, pp.79
Cellulose microspheres (CMs, diameters 10-1000 m) have been used as stationary phases in chromatography, substrates for ion exchange applications, supports for protein immobilization and solid-phase synthesis, and drug loading and release materials.2 Furthermore CMs are biocompatible and have been used in many biomedical applications as varied as blood filtration3,4 and the dressing of wounds. Blood is normally sterile and the presence of bacteria in blood is a condition known as bacteremia. Bacteremia can be caused by burns, injuries, local infections, surgical procedures, and the use of catheters or needles. If undetected and untreated, the immune response to bacteremia can result in sepsis, septic shock, and multiple organ failure. Septic shock and multiple organ failure as a result of hospital-acquired bacteremia is a leading cause of death in intensive care units.5 Zinc(II) bisdipicolylamine complexes (Zn2BDPA, Figure 1, Panel A) are capable of selectively binding to negatively charged phosphate amphiphiles displayed by bacterial cells.6
In this study we aimed to develop Zn2BDPA-derivatized CMs with an ultimate goal of obtaining selective sorbents for the treatment of bacteremia through extracorporeal blood filtration. To this end we have investigated the preparation of CMs through the thermal regeneration of cellulose from water-in-oil emulsions of viscose. Native CMs were then activated to display epoxy, amino, and carboxylic acid functionalities. We then tried to couple amine and carboxylic acid reactive BDPA ligands with these activated CMs. Elemental analysis and FTIR spectroscopy confirmed the formation of BDPA-CM conjugates. These Zn2BDPA functionalized CMs were then shown to bind to green fluorescent protein (GFP) expressing bacterial cells through fluorescence microscopy (Figure 1, Panel B and C).
Acknowledgement: We gratefully acknowledge financial support from TÜBİTAK (Project 118Z442).
Footnotes and References:
1) Undergraduate student researcher
2) Gericke, M.; Trygg, J.; Fardim P. Chem. Rev. 2013, 113, 4812−4836.
3) Wang, S.; Yu, Y. “Bioactive bead type cellulosic adsorbent for blood purification”, 2013 in Cellulose-Medical, Pharmaceutical and Electronic Applications. IntechOpen.
4) Weber, V. et al. “Functionalization and application of cellulose microparticles as adsorbents in extracorporeal blood purification.” In: Macromolecular Symposia. Weinheim: WILEY‐VCH Verlag, 2010. p. 90-95.
5) Mayr, F.B.; Yende, S., Angus D.C. “Epidemiology of severe sepsis” Virulence 2014, 5(1), 4-11.
6) Turkyilmaz, S.; Rice, D.R.; Palumbo, R.; Smith B.D. Org. Biomol. Chem. 2014, 12, 5645-5655.