Speaking just ahead of the company's acquisition of 100 per cent of its UK subsidiary pSiMedica today, the company's managing director, Gavin Rezos, said that the BioSilicon material is cheap to manufacture, biodegradeable, safe to administer and offers exquisite control over the rate of release of the drugs it carries.
BioSilicon takes the form of nanostructured porous silicon that can be machined into powders, microspheres, or just about any other structure whilst retaining its ability to carry and release active components. It is just about to start clinical trials as part of a brachytherapy (short range intratumoural radiotherapy) for liver cancer.
Rezos told In-PharmaTechnologist.com that that one of the main attractions of BioSilicon is the range of compounds it can carry, as well as the fact that it does not have to be chemically bonded to its payload. This means that there is no need to alter the manufacturing process for the drug it carries and, once a dossier has been filed with the relevant regulatory authorities, development of BioSilicon-based versions of existing drugs should be fairly straightforward.
In drug delivery applications, BioSilicon has significant advantages over rival polymer slow release drug delivery systems in animal trials. For example, it boasts higher loading rates, and the rate of release (achieved as the BioSilicon breaks down in the body), can be controlled to extend from days to months.
The structure of the material prevents dose dumping - the release of a higher dose of drug after it is first administered which then gradually tails off. Moreover, unlike polymers silicon can carry an electrical current, which can be harnessed to alter the rate of break down. In the future, this property could be used to incorporate sensors into a BioSilicon implant, which could then respond to its environment and release drug appropriately.
pSivida's core focus is the development of controlled slow release drug delivery products through pSiMedica and brachytherapy through another subsidiary, pSiOncology.
In brachytherapy, pSivida should be able to start a trial of its BrachySil product in Singapore before the end of the month. The product is made by concentrating phosphorus in the silicon and placing it in a reactor, creating the radioactive isotope 32-P. This has fewer side effects compared with currently used radionuclides due to its shorter range, which also makes it safer for the person delivering the treatment.
Rezos noted that 32-P is also commercially more practical having a much longer half life (14 days) compared to yttrium 90 (64 hours), which is widely used in brachytherapy. The market targeted by BrachySil is tipped to reach $1 billion in 2005.
Slow-release drug delivery is a much larger opportunity, with the market valued at more than $20 billion, although the use of the technology in this setting is not so advanced as in brachytherapy. pSivida has a collaboration in place with UK drug delivery firm PowderJect to look at applications of BioSilicon in DNA vaccine delivery, while a project with Epitan looking at the delivery of melanotan for skin tanning.
Another potential application for the material is in diagnostics. Many cancers are detectable through chemical markers released into the bloodstream usually detected by diagnostic tests in pathology laboratories. By placing porous silicon mirror particles, smaller than a pin-head, containing quantities of targeted antibody, the antibody capture mechanism would generate a change in reflectivity as the relevant marker accumulates on the BioSilicon surface.
The patient could externally detect this change using a handheld device, avoiding the need for routine blood tests and making very early detection of disease re-establishment possible.
Non-core technologies, which include applications in orthopaedics, tissue engineering, and smart chip and electronic applications will be licensed out, said Rezos. In fact, the tissue engineering and orthopaedic businesses may be sold off as a package to companies with a standing in these areas, he predicted.
pSivida has a materials exchange research agreement in place with Implex, a US orthopaedic products company for the development of improved orthopaedic devices which reduce the healing time for bone breaks and fractures, and decrease muscle wastage at the point of repair.
Meanwhile, in the tissue engineering sector, pSivida has a research materials agreement with the McComb Foundation for the use of BioSilicon as a scaffold for skin cell lines used in wound healing and burns. It also has two agreements with the Singapore General Hospital to assess cell proliferation and metabolism and with Cytomatrix in the US for stem cells to treat patients following radiotherapy and chemotherapy.
Safety issues
One issue facing pSivida will be instilling confidence that BioSilicon is safe, in the wake of the negative press surrounding silicone implants over the last years and the more recent concerns voiced about nanotechnology.
Rezos noted that a clear distinction must be made between the silicone use in implants and pSivida's porous silicon, which breaks down in the body to form silicic acid, a substance which, he said, is encountered everyday in the diet. pSivida has already conducted animal studies in which high doses of BioSilicon have been ingested over extended periods, with no evidence of toxicity.
Meanwhile, many of the concerns surrounding nanotechnology have related to its accumulation in tissues such as the brain. This should not occur with BioSilicon as it is biodegradeable, although it may be an issue with carbon-based alternatives to pSivida's material, such as carbon nanotubes.
Carbon nanotubes are being explored as potential drug delivery vehicle, with interest driven by their apparent (and so far unexplained) ability to deliver directly to the nuclei of cells, but work is still in the very early stages. Meanwhile, Canadian company CSixty is focusing on the use of carbon 'buckyballs,' although these have yet to start human trials.