Crafty Carriers: Armoring vesicles for more precise and reliable drug delivery

Transporting drugs into the body can be hit-or-miss because many delicate molecules break down before they reach their target. In an attempt to develop protective drug-delivery tools, materials scientists have now fabricated micron-size polymer vesicles that are sturdy enough to navigate the bloodstream unscathed and yet release their cargoes on target.

In the past few years, several research groups have focused on developing drug carriers called liposomes (SN: 1/18/03, p. 43: Delivering the Goods). The membranes of these hollow spheres consist of fatty molecules—lipids—in the same arrangement as that of similar lipids in a living cell’s membrane. However, liposomes themselves are fragile; their membranes are “as thin as soap bubbles’,” notes Richard Jones of the University of Sheffield in England.

To fabricate tougher liposomelike vesicles, Timothy Deming at the University of California, Santa Barbara and Darrin Pochan of the University of Delaware in Newark enlisted polymers of amino acids, the building blocks of proteins. To make the polymers behave as lipids do, the researchers designed the amino acid chains to have one water-repelling and one water-attracting end.

When added to a water solution, these polymers spontaneously assembled into vesicles. However, instead of having two molecule layers, as membranes of a regular liposome do, the new membranes had three layers. The added thickness makes the vesicles tougher than liposomes, the researchers report in the April Nature Materials.

“We envision that these materials [will] posses attributes useful for applications in biotechnology and medicine,” say the researchers.

Although thickening the armor on vesicles can better protect their contents, it creates a problem for getting the drugs out of the vesicles on cue. Deming and his colleagues overcame that challenge by tweaking the amino acid composition of the polymer’s water-attracting segment to make the polymers responsive to a change in acidity, or pH.

The researchers next enclosed a fluorescent dye inside vesicles formed from the new polymer and lowered the pH of the solution containing the spheres. This disrupted the membranes, releasing the dye. Future alterations in the amino acids could tailor the vesicles to respond to various pH environments, such as in the gastrointestinal tract or a cancer cell.

The response to pH is akin to the way many viruses infect cells, say the researchers. The acidic cellular interior triggers the virus’ protein coat to open and release the invader’s genes.

Jones says that vesicles made of amino acids could be an “altogether more useful product” for drug delivery than those made of liposomes.

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