New carrier for drug administration
Researchers at Institut Lavoisier, based at the Université de Versailles, France, have announced successful tests on a new carrier for drug administration.
Medicines are often encapsulated so the substance is released slowly into the human body, or only becomes active in specific organs. According to the team at Versailles, there are problems associated with the two approaches currently employed. The ‘organic’ route involves drug molecules being enclosed in biocompatible dendritic macromolecules or polymer carriers, but this does not achieve controlled release due to the absence of a well-defined porosity. Post-synthesis treatment of the product is therefore required.
Meanwhile, the ‘inorganic’ method involves a carrier manufactured from silicate solid materials, or zeolites, where ‘there is a rigid and well-defined porosity’, explains lead researcher Gérard Férey. ‘But the inorganic wall is not favourable for host-drug interactions, [therefore], the walls are coated with organic siloxanes. This grafting has a significant disadvantage because the coating on the internal surface of the pores induces a decrease in volume and therefore of drug-loading capacity.’
The new porous crystalline nanomaterials developed last year by the team at Versailles, MIL-100 and MIL-101 (see Materials World, February 2006, p16-17), are metal-organic frameworks (chromium compounds with a range of organic components, such as carboxylates, phosphonates or sulfonates). These hybrid materials combine the advantages of both the above approaches and provide carriers with large cavities.
Férey says, ‘Due to their mixed organic-inorganic skeleton, there is no need for post-synthesis treatment or further grafting [with organic molecules] – this preserves the initial porosity. Chromium is toxic, but structures exist with other cations and we have proved non-toxicity for organisms.’
He adds, ‘[Effective drug] storage must combine large volumes for the cages for high loading and medium interactions with the drug that are strong enough to allow storage but weak enough to be broken in a physiological medium. It is the kinetics of breaking bonds which determines the time for release.’
Tests were undertaken with the painkiller Ibuprofen, which was absorbed from a solution in hexane. The MIL-101 lattice was able to carry what the team claims is an astonishing quantity of the drug – 1.4g per gram of the carrier – and release it within six days under physiological conditions.
‘Ibuprofen is considered by pharmacologists as a model and molecule of reference in this area,’ explains Férey.
By varying the components of the lattice, the researchers hope to tailor the pore shapes and sizes for individual pharmaceuticals and the desired dosage.