The volume-enclosing (Voxel) microstructures are an enticing prospect for drug delivery because they can be engineered to deliver a range of drug combinations or doses. The drug industry is increasingly focused on delivering drugs in combination to make patient treatment easier, improve efficacy and - faced with a reduction in new active substances coming through to market - extend the patented lifespan of older compounds.

The researchers, from the University of Southern California's Information Sciences Institute, create the Voxels by etching two-dimensional patterns into polysilicon layers on top of a thin film of gold using a technology developed by French micro-electromechanicals specialist Memscap. They then used a combination of magnetics, water pressure, drying and capillary action to fold the patterns into hollow 3D structures of around 20 to 30 microns in diameter.

Project leader Professor Peter Will, an ISI Fellow, told in-PharmaTechnologist that the technology has considerable potential in drug delivery. He said that: "[Voxels] are of a small programmable size so that a single [one] has a metered dose and they are so small that they are injectable by a normal thin needle."

The use of toxic drugs and complex biologics in indications ranging from cancer to autoimmune disorder mean that accurate delivery and release is becoming a key focus for the pharmaceutical industry. For example, while anti-angiogenic medications have huge potential in preventing tumour growth or in arresting the development of acute macular degeneration, it is important that they do not interfere with normal blood vessel development.

Multi-drug regimens

Will also commented that because the size of the Voxels can be programmed, infusions containing a range of different dosage sizes could be produced. Such an approach would be ideal for complex multi-drug regimens.

He also said that: "the smallest Voxels made so far have been 20 microns on a side but much smaller is possible," adding that "forming them and getting them to close enough to be sealed is step one. We have not yet 'cemented' up the sides of the Voxels. That is step two."

Although the project is still at a relatively early stage, the team is already considering methods of stimulating drug release. Professor Will explained that either ultrasonics or MRI could be employed to rupture the Voxels, thereby allowing targeted drug release. The researchers anticipate that release would be dependent on the size of the particle and duration of exposure to, for example, the ultrasound stimuli.

Will said that the team has also: "looked at biodegradable polymers but would prefer to rupture on demand locally by a focussed beam."

Will added that: "while the method we used could make a large number of Voxels per wafer," the expense associated with such a technique, in terms of the cost of raw materials, masking and processing, would not be suitable for mass production.

He suggested that biocompatible polymer films could be used in place of the polysilicon wafers, but added that this would require further research and funding. He went on to say that with appropriate financial resources initial trials could be undertaken after three years of further work.