Featured Article Academic Journal Main Category: MRSA / Drug Resistance Also Included In: Biology / Biochemistry Article Date: 06 May 2012 – 12:00 PDT

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The scientists have been working towards this goal by developing a nanoparticle that invades the immune system, targeting the infection sites, and subsequently release a focused antibiotic attack.

According to leading author, Aleks Radovic-Moreno, who is an MIT graduate student, this strategy would lower the side effects of some antibiotics and protect the beneficial bacteria that commonly live in the human body.

The new nanoparticles were created from a polymer capped with polyethylene glycol (PEG), which is commonly used for drug delivery due to its nontoxic properties and because it can help to transport nanoparticles through the bloodstream without being detected by the immune system. The researchers then induced the particles to specifically target bacteria. Previous attempts to target particles to bacteria by giving them a positive charge that attracts them to bacteria’s negatively charged cell walls have not been successful, given that the immune system tends to clear positively-charged nanoparticles from the body before they can encounter bacteria.

The team managed to overcome this hurdle by designing antibiotic-carrying nanoparticles, which can switch their charge depending on their environment, for instance, whilst circulating in the bloodstream, the particles’ charge is slightly negative, yet on encountering an infection site, they gain a positive charge, which allows them to bind tightly to bacteria and release their drug payload.

The switch is invoked because of the slightly acidic environment surrounding bacteria. Infection sites can be slightly more acidic compared with normal body tissue, because the bacteria that cause disease reproduce rapidly and deplete oxygen. Insufficient oxygen levels, however, trigger a change in bacterial metabolism, which prompts them to generate organic acids. The body’s immune cells try to assist – neutrophils cells start producing acids so as to to consume the bacteria.

The nanoparticles have a pH-sensitive layer that is made of long chains of the amino acid histidine just below the outer PEG layer. When the pH-level fall from 7 to 6, i.e. when it becomes more acidic, the polyhistidine molecule tends to gain protons that give the molecule a positive charge.

The nanoparticles start releasing their drug payload, which is embedded in the particle’s core, once they bind to bacteria. The researchers designed the particles to deliver vancomycin, which is used to treat drug-resistant infections, However, it is possible to modify the particles to deliver other antibiotics or combinations of drugs. With increasing acidity, many antibiotics tend to lose their efficacy. However, the team discovered that antibiotics carried by nanoparticles retained their potency better than traditional antibiotics. The current version of nanoparticles discharges its drug payload over one to two days.

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