Pharmacology

The researches find that the An organic molecule composed of simple sugars could become a potent weapon in the fight against rising antibiotic resistance, according to EU-funded researchers who have developed a novel, targeted drug-delivery technique to treat deadly tuberculosis and other lethal pathogens. The EU-funded CYCLON HIT project investigated cyclodextrins cyclic oligosaccharides whose molecular composition is similar to common table sugar as a nanotechnology-engineered carrier for antibiotics and other drugs.

Rising antibiotic resistance

They discovere that cyclodextrin nanocarriers develop not only to efficiently encapsulate and protect antibiotics to combat resistant bacteria; but that these molecules also possess unique antimicrobial properties of their own. They adopt a totally innovative approach in which cyclodextrins are not just used as nanocarriers of drug combinations but they also play an active role in fighting infection by interfering with the mechanism through which bacteria invade cells.”

Ruxandra Gref; project coordinator; Centre National de la Recherche Scientifique in France Targeting tuberculosis; one of the leading causes of death worldwide which claims more than 1.5 million lives each year; the CYCLON HIT team investigated a method to deliver antibiotic-enhanced cyclodextrin nanoparticles directly into the lungs; where the Mycobacterium tuberculosis pathogen accumulates in humans.

Unique antimicrobial properties

This highly specialised bacteria uses part of the membrane of cells called lipid rafts to enter lung tissue where it is able to take up residence inside defensive cells known as macrophages; effectively hiding itself within the body’s own immune system. ‘Using this ingenious mechanism, the pathogen invades and persists inside macrophages despite their role in killing foreign bodies. They found that engineered cyclodextrins also preferentially locate at lipid rafts and act as a shield against pathogen penetration without any toxicity for the body;’ Gref says.

Cyclodextrins can therefore be engineered to perform two life-saving functions: preventing pathogens from invading cells; and delivering antibiotics and other medications to infected cells; providing a potent dual-action weapon against disease. Furthermore; a patented nanoparticle developed by the CYCLON HIT researchers made ;from β-cyclodextrin nanoparticles could enable the administration of antibiotic drug combinations directly into the lungs via an inhaler rather than patients having to ingest slow-acting and less-effective pills.

Following the failure of first-line antibiotics; multidrug-resistant tuberculosis is currently treat with chemotherapy or second-line antibiotics such as ethionamide in combination with other drugs. But patients often find it difficult to comply with treatment regimens that can require taking more than 10 000 tablets over a two-year period; frequently with debilitating side effects.