Development of novel silica nanoparticle designs for antibiotic delivery Asier Rodriguez Muguruza 1 , Jessica. M.A. Blair 2 , Zoe Pikramenou 1 1 School of Chemistry, University of Birmingham, UK, 2 Institute of Microbiology and Infection (IMI), University of Birmingham, UK Antimicrobial resistant (AMR) is the results of bacterial cells being able to overcome the effect of antibiotics, causing substantial morbidity and death globaly. 1 The design of new antibiotics is a time-consuming process with low success due to the rapid acquisition of resistance by bacteria to new drugs. However, the use of drug delivery systems has been proposed as a promising solution to overcome AMR. Silica nanoparticles (SiO 2 ) in particular, have attracted the attention of the research community due to their facile synthesis, tuneable morphology and surface composition and high biocompatibility. Mesoporous SiO 2 have been the preferred choice for drug delivery due to their porous structure; nevertheless, if pores are not capped, burst cargo release is observed. 2 Furthermore, the effective delivery of antibiotics relies on the nanoparticle-cells inspections, most of the time, overseen in the current literature. In this work, we have explored alternative framework and surface designs for the development of non-porous silica nanoparticles with enhance antibiotic delivery. Addition of organic building blocks within the frameworks or via templating strategies have resulted in SiO 2 with higher cargo loading and release. Furthermore, surface modification of SiO 2 with chelators 3 and meta complexes have increased cell- nanoparticle interactions, being able to target bacterial surface receptor, and in this way improve the interactions of nanoparticles containing antibiotics, that in their free form are not able penetrate the Gram-negative bacteria cell wall, and hence, not being active.
References 1. M. Darby, E. Trampari, P. Siasat, M. S. Gaya, I. Alav, M. A. Webber and J. M. A. Blair, Nat. Rev. Microbiol. , 2022, 21 , 280–295. 2. M. Vallet-Regí, F. Schüth, D. Lozano, M. Colilla and M. Manzano, Chem. Soc. Rev. , 2022, 51 , 5365–5451. 3. A. R. Muguruza, A. di Maio, N. J. Hodges, J. M. A. Blair and Z. Pikramenou, Nanoscale Adv. , 2023, 5 , 2453–2461.
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