OPINION | DERMATOLOGY |
TO THE SKIN O
DELIVERING DRUGS
Delivering drugs through the skin is a well-known technique for simplifying administration and avoiding first-pass
metabolism. But what about when the aim is to deliver drugs to the skin? Peter Charlish examines some recent developments in this area.
NE OF THE MANY challenges of treating cancer is how to deliver anti-cancer drugs to precisely those tissues in the body where they
are needed, while at the same time sparing other tissues from their toxic effects. In the case of skin cancer, you could be
forgiven for thinking that this goal would be relatively easy to achieve: after all, all you have to do is apply the drug to the affected skin in a suitable vehicle, right? Wrong, unfortunately. There are many reasons why such an
approach is not practical. For example, the drug may be too toxic to apply externally. An externally-applied drug could easily be transferred to the fingers and so, could come into contact with the mouth or the eye, with potentially serious consequences. Another reason may be that, if the diseased cells lie below the surface of the skin, as in the case of skin cancer, and the drug is unable to penetrate through the skin, then external application is likely to achieve little.
New research Recently, researchers at Northwestern University in Evanston and Chicago, Illinois, reported a new technique for delivering
small interfering RNA
PETER CHARLISH Principal Analyst, Informa Business Information
email:
peter.charlish@
informa.com 60 ❚
(ribonucleic acid) molecules through the skin, where they target a gene that is thought to promote the growth of tumours. Small interfering RNAs (siRNAs) are a class of double-stranded RNA
September 2012 |
prime-journal.com
molecules, approximately 20-25 nucleotides long, that occur in both plants and animals, where they are thought to have a number of functions, including regulating the expression of genes with a complementary nucleotide sequence. This property is currently being explored as a possible way of treating cancer, as well as as a research tool. RNA molecules will not normally pass
through the skin, so to achieve transdermal delivery of siRNA, the US researchers turned to the science of nanotechnology. They took gold nanoparticles with a diameter of approximately 13 nm and surrounded them with a shell of covalently immobilised siRNA designed to inhibit the expression of epidermal growth factor receptors (EGFR). These so- called spherical nucleic acid (SNA) constructs were found to penetrate freely almost 100% of keratinocytes studied in vitro, as well as through the skin of live mice. Importantly, there was a significant reduction in EGFR mRNA expression and almost complete inhibition of EGFR protein levels in the relevant tissues. Similar results were obtained in experiments using human skin equivalents. Of particular significance was the fact
that, in the intact skin studies, the nanoparticles were delivered using a commercial moisturiser product (Aquaphor, manufactured by Beiersdorf) as the delivery vehicle, and that they did not require the use of barrier disruption or transfection agents, such as liposomes, peptides, or viruses. In the in vivo
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