Picking the bones of drug delivery

Supercritical CO2 offers a novel route to controlled protein release.

Supercritical carbon dioxide is becoming an increasingly popular solvent in industrial processes, and is often used to extract organic compounds such as caffeine from natural products. But researchers from Ohio State University, US, have found a way to use it for the opposite process — forcing chemicals into a polymer. The process may be the key to making implantable reservoirs for controlled release of drugs which double up as bone replacements, the team says.

David Tomasko’s team is working on medical implants made from polymethyl methacrylate (PMMA), which is often used in bone replacement implants. Embedding drugs into these implants would give them a double effect — they would both replace missing bone and deliver drugs to prevent inflammation or infection following surgery. If bone had been removed as a result of cancer, an impregnated implant could also deliver anti-cancer drugs to the site.

The technique is fairly simple: Tomasko’s team swabbed a protein solution onto a coin-sized disc of PMMA, then placed the disc in a glass tank which they flooded with supercritical CO ₂.The protein was driven 30µm into the surface of the PMMA, with the CO ₂ acting as a lubricant to push the proteins between the tightly-packed polymer chains of the plastic. The structure of the protein was apparently not affected by the process, the researchers say. Another effect was entirely unexpected: the inside of the disc foamed up into a series of tiny voids. The foaming effect turned out to be controllable: the faster the engineers turned off the CO ₂, the more voids were created. Tomasko believes that these voids could be used as an extra reservoir for drugs.

The ability of the CO ₂ to embed the proteins without changing their structure is very significant, because the substance has yet another property - it sterilises the surface of the polymer. Surgical implants are generally sterilised with heat, radiation or disinfectant chemicals, all of which can change the structure of drug active ingredients.

There is still some way to go before these materials are usable in surgery. Tomasko is now trying to determine whether drug molecules actually remain effective after being embedded in the plastic. He is working with biodegradable materials which could be combined with the PMMA to form a reservoir that would release the drugs once they had been implanted.

Stuart Nathan