## Special Delivery

Drug molecules, without special intervention, don't apply only where we want them to. Indeed, late last year this fact landed pharmaceutical giant Reckitt Benckiser in trouble with the Australian regulator. Their "specific pain" range, despite bold claims on the packaging, was deemed to not target back pain, migraine or indeed any other specific pain. As a result, the premium pricing was ruled misleading and earned the company a AU\$6 million fine. Pharmaceutical marketing departments will likely be unhappy that a regulator has decided the standard approach of deploying medication via simple blood circulation should no longer be represented as targeted.

Of course, this issue isn't simply about misleading consumers; truly targeted drug delivery may be the only effective means of treating certain conditions. This fact has been behind the growing use of liposome packaging, and the more recent emergence of ultrasound techniques to cross the blood-brain barrier and treat brain disease. However, the importance of having drug activity focus where required may well be matched by the need to avoid impact elsewhere. An important example would be in the treatment of cancers using cytotoxic chemotherapy. Such agents don't simply harm cancer cells, but by acting against the process of mitosis, will disproportionately impact all cells that rapidly divide, including those in the bone marrow, hair follicles and digestive tract. In the UK the mortality impacts of such therapies are themselves tracked using increasingly sophisticated monitoring and reporting. Clearly, limiting cytotoxic agents to more precisely target only the disease would reduce cancer-related mortality.

Recent research in targeted drug delivery has explored the application of nanotechnology. One focus has been on using DNA origami to construct nano-caged medications (or, more sensationally, nano-bots) that will release their payload only in the presence of a target cancer cell. Results from human subjects are not yet available, although a commercial collaboration is now reportedly underway. Another focus has been to exploit the properties of existing nanoscale organisms to create novel treatments. The Magnetococcus marinus bacterium has been found to be magnetically guidable into oxygen-depleted tumour regions previously resistant to treatment. Again this promising therapy has not yet released trial results in humans.

However, a different microbe-based intervention published human results in December 2016. Here, a derivative from a light-activated deep-sea bacteriochlorophyll known as WST11, has been applied in a photo-dynamic therapy for prostate cancer. The treatment involved minimally invasive optical fibres being inserted into the prostate to activate the therapy directly at the site of interest. This had the impressive outcome of boosting complete remission to nearly half of all cases compared with just 14% in the control group. This is a clear example of a novel targeting strategy delivering not just medication, but groundbreaking results for patients as well.

References

Lai, F., Fadda, A.M., Sinico, C. (2013) Liposomes for brain delivery. Expert Opin Drug Deliv. doi:http://dx.doi.org/10.1517/17425247.2013.766714

Zhao, Y.Z., Lu, C.T., Li, X.K., Cai, J. (2013) Ultrasound-mediated strategies in opening brain barriers for drug brain delivery. Expert Opin Drug Deliv. doi:http://dx.doi.org/10.1517/17425247.2013.787987

Douglas, S.M., Bachelet, I., Church, G.M. (2012). A logic-gated nanorobot for targeted transport of molecular payloads. Science. 2012 Feb 17;335(6070):831-4. doi: 10.1126/science.1214081

Martel, S. et al. (2016) Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nature Nanotechnology 11, 941-947(2016) doi:10.1038/nnano.2016.137

Emberton, M. et al. (2016) Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. The Lancet Oncology doi:http://dx.doi.org/10.1016/S1470-2045(16)30661-1

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