Surface and framework modification of silica nanoparticle for efficient delivery of antibiotics

Rodriguez Muguruza, Asier ORCID: 0000-0003-4169-5024 (2024). Surface and framework modification of silica nanoparticle for efficient delivery of antibiotics. University of Birmingham. Ph.D.

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Abstract

Antimicrobial resistance is a growing health concern being the cause of higher morbidity and mortality worldwide. Alongside the increased number of resistant bacterial strains identified and the reduced number of new antibiotics in the pipeline, the development of new antimicrobial therapies is crucial. Silica nanoparticles present unique properties for the design of novel drug delivery systems. The chemical versatility of their surface and framework proposes an advantage for the design of innovative antibiotic delivery systems.
Hereby, we present different approaches for the development of novel silica nanoparticles for the efficient delivery of antibiotics against Gram-negative bacteria. Firstly, surface functionalization of silica nanoparticles led to a novel drug delivery system able to deliver an antibiotic inside Gram-negative bacterial cells, that in its free form is not active due to the reduced permeability of Gram-negative bacteria. Furthermore, the simultaneous inclusion of a ruthenium(II) luminescent metal complex alongside an antibiotic allowed the tracking of the therapeutic nanoparticles. Further Fe3+ cation complexation to the ligand attached to the nanoparticle surface is determined to be an excellent approach to enhance the uptake of nanoparticles in bacterial cells driven by nutrient uptake systems expressed in the bacterial membrane. Another studied approach consisted of the modification of silica nanoparticles framework with spiropyran derivatives to achieve photoresponsive particles that displayed light triggered antibiotic release against urinary tract pathogenic bacterial cells.
Finally, two different approaches for the modification of nanoparticle’s framework were investigated by development of polysilesquioxane nanoparticles and micelle-driven encapsulation in order to enhance the loading and release of a model hydrophobic antibiotic resulting in nanoparticles with better antibiotic delivery performance than traditional non-porous and mesoporous silica nanoparticles.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):