Scientists in Japan have developed a unique way to control the size of lipid-based anticancer drug carriers. Using this method to create mesoscale drug carriers could lead to more efficient targeting of tumours. 

Mesoscale drug carriers have a diameter between five and 100 nanometres and have become popular in drug delivery as they accumulate in tumour tissues and inflammatory sites after being injected into the blood. Their small size means that they move in stealth through the body without creating an immune response and can escape from the bloodstream through leaky blood vessels that surround tumours but do not escape through normal blood vessels. 

Tatsuya Murakami at Kyoto University and colleagues based the design of their drug carrier on high-density lipoprotein (HDL), which transports cholesterol through the blood. By varying the amount of loaded drug, Murakami found they were able to control the size of the drug carrier, in this case HDL, so that it fell into the mesoscale. 

The team prepared the drug carriers by mixing together a serum protein, known as apolipoprotein A, with phospholipids. The serum protein wraps around the phospholipids in a continuous helical nature giving the carrier a diameter of 13 nm. The crucial factor, says Murakami, is the amount of phospholipids added which needs to be much greater than that used to prepare HDL for general biochemical studies. The anticancer drug, doxorubicin, is then incorporated into the drug carrier by simple mixing with the final size of the loaded carrier controlled by the amount of drug added. 

HDLs have particular potential as drug carriers because, unlike other materials, including micelles and liposomes, they are intrinsically biocompatible and do not have to be coated with polyethylene glycol (PEG), which is known to weaken the functions of molecules introduced to the surface of drug carriers, explains Murakami. 'The absence of PEG modification means that it may be possible to endow the HDLs with further functions through genetic and/or chemical modification,' he adds. 

Patrick Shahgaldian at the University of Applied Sciences Northwestern Switzerland in Muttenz sees promise in the work. 'Self-assemblies of phospholipids, represent one of the most promising ways to design cargo systems able to safely carry drugs to their therapeutic target. These results might be valuable for the development of HDLs in drug delivery,' he says. 

Sarah Corcoran 

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