Treatment -Pathogen Infection

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Summary UCLA researchers in the Department of Chemistry and Biochemistry and Department of Medicine at the David Geffen School of Medicine have developed a new nanotherapeutic for the treatment of intracellular and extracellular pathogens. Background Drug-resistant pathogens such as Mycobacterium tuberculosis and Francisella tularensis, the pathogen that causes tularemia, necessitate the use of long-term antibiotic therapies or combined drug therapies to clear the infection, often requiring hospitalization. Current therapies, such as fluoroquinolone drugs, require high doses leading to side effects and can be rapidly metabolized and excreted by patients. Mesoporous nanoparticles offer distinct advantages over other drug delivery systems (e.g. liposomes, alginates, etc.) and the drug alone as they are more stable, can be targeted to specific cells, uniformity, inherent lack of toxicity, and have large drug cargo capacity (up to 50% of its weight). However, while this technology has recently been developed for cancer therapeutics, it has not yet been tested for efficacy for the treatment of infectious disease. Innovation Prof. Marcus Horwitz and Prof. Jeffery Zink and colleagues at UCLA have developed a new mesoporous nanoparticle therapeutic system that can specifically delivery antibiotics to macrophages for the treatment of tularemia and other intracellular infections. Furthermore, they were able to design a ‘snap-top’ system that was able to retain the drug until appropriately delivered to the inside of the cell. They demonstrated in a mouse model for pneumonic tularemia (a potential bioterrorism threat) that their system exhibited log-fold reductions in colony-forming units in various organ systems at significantly lower drug concentrations compared to administering the drug alone. Applications For the treatment of various pathogens including Mycobacterium tuberculosis and Francisella tularensis Deliver single or combined antibiotic therapies Advantages  The mesoporous nanoparticle ‘snap-top’ system is more efficacious than an equivalent amount of free drug Targets macrophages, the host cells for a variety of intracellular pathogens, thereby increasing the therapeutic index Controlled intracellular drug release  Various routes of administration and fully biodegradable Inherently non-toxic