Drug delivery: Made to order DEVISING effective drugs is only half the battle faced by pharmaceutical companies. The other half is delivering them to the place in the body they are needed. Pills and potions are easy to pop, but they must then run the gauntlet of the gastrointestinal tract, with its hostile acids and enzymes. Injections bypass that difficulty, but they are unpleasant for the patient and, if they have to be carried out repeatedly, can be damaging. Skin patches and nasal sprays are alternatives for some medicines. But all these methods share a problem. The drug is generally being given to the entire body, when it is actually wanted in only one, specific place. Some researchers, therefore, are exploring an alternative: building tiny factories that make and release a drug precisely where it is needed. Among these investigators is Daniel Anderson, a chemical engineer at the Massachusetts Institute of Technology. And as he reports in Nano Letters, he and his colleagues have built a device which might do just that. Popping a pill factory Dr Anderson's drugmaking machine is a simplified, artificial version of a living cell, albeit one that cannot reproduce. The cell's outer membrane is made of molecules called phospholipids, which are similar to those in the membrane of a natural cell. In the right conditions, an emulsion of these molecules will organise itself into small spheres, known as vesicles, that contain part of the liquid the phospholipids were suspended in. Dr Anderson arranged for these conditions in a liquid that contained ribosomes - the subcellular machines that manufacture proteins. It also contained pieces of DNA that carried a gene for a particular protein; a plentiful supply of the raw materials for making both proteins and the messenger molecules that carry DNA's instructions to the ribosomes; and a set of enzymes needed to make the whole shebang work. The protein in question was not actually one that might be useful as a drug. Instead it was a molecule called green fluorescent protein. This is a workhorse of molecular biology that is used because its presence can easily be detected by its tendency to glow green when suitably illuminated. And green the vesicles did indeed glow, showing that Dr Anderson's protein assembly line was running smoothly. The next phase was to bring the factory under control, so that it could be switched on at will, and thus act only where and when needed. To do so, the team encased the DNA in a special chemical cage before they encapsulated it. This cage was designed to break down when illuminated by ultraviolet light. Only once that had happened could the DNA become active. And when Dr Anderson injected the modified vesicles into mice and then shone ultraviolet light of a wavelength that can pass through flesh at some of them, he found the tactic worked. Mice so illuminated produced green fluorescent protein. Those that were not, did not. Having proved the point, Dr Anderson has gone on to look at the yield of his tiny factories. He has made them in a range of sizes, from 400 nanometres (billionths of a metre) across, to 100 nanometres. Up to a point, smaller is better. The 400-nanometre version turned out an average of 190 protein molecules per vesicle. The 170-nanometre version, a thirteenth of the volume, managed 81 molecules. That is good news, because smaller vesicles can travel through blood capillaries more easily, and would thus be simpler to deploy. There was a limit, though. The 100-nanometre vesicles produced no protein whatsoever. The next stage is to test the nanofactories with DNA that makes proteins which might actually act as drugs - anticancer antibodies, for example. That should be a formality; from a ribosome's point of view, one protein is much like another. Whether the system can then be turned into a practical method of drug delivery is more questionable. But if it can, a new and valuable weapon will have been added to pharma's armamentarium.