Staphylococcus aureus implant-associated biofilms: Development of a novel nanoparticle-based drug delivery system

Bacterial biofilms are currently an increasing concern for modern medicine due to the escalating figures of antimicrobial resistance and the high demand for implantable medical devices. When a medical device enters the human body, it is prone to infection and, eventually, to biofilm formation. The current therapy to treat bacterial biofilms is solely focused on the administration of conventional antibiotics, which fails to target the extracellular polymeric substances (EPS) matrix. The EPS matrix is the first barrier that antibiotics encounter. This structure protects bacterial cells within the biofilm by hindrance the diffusion of antibiotics into deeper layers of the structure. Hence, current therapies to treat implant-associated biofilms commonly fail, and the removal of the device is frequently required. Several bacterial species are associated with biofilms formed on implantable medical devices, such as Pseudomonas aeruginosa and Staphylococcus spp. Amongst these, Staphylococcus aureus biofilms are being highlighted due to their high prevalence and high mortality and morbidity rates. In the present work, we proposed innovative strategies based on the encapsulation of matrix-disruptive agents (N-acetyl-L-cysteine and caspofungin) and bactericidal agents (moxifloxacin and farnesol) into lipid nanoparticles. The nanoparticles were functionalized with ᴅ-amino acids to target and disrupt the biofilms. The developed nanosystems were studied alone and in combination, as a multi-target strategy, to target both the EPS matrix and the bacterial cells within the biofilms. The formulations developed in this thesis were evaluated according to their physical characterization, biocompatibility and antibiofilm efficacy. In vitro and in vivo studies revealed the potential of the developed nanosystems to improve current therapies toward the eradication of clinically relevant bacterial biofilms.

Publication year:2022

Accessibility:Closed