Everyone agrees that some of the key applications of nanotechnology will be in medicine. Within medicine, drug delivery is an obvious target. So when can we expect to see nano-enabled medicines on the pharmacy shelves? The answer, as usual, depends on what you mean by nanotechnology. Many people have welcomed Abraxane™, which received FDA approval for use for breast cancer earlier this year, as the first nano-drug. But a number of other drugs already in clinical use have just as much right to the nano- label.
Ruth Duncan gives a useful list of nano-medicines in current clinical use in an article in Nano Today – Nanomedicine gets clinical (I’ve already referred to this article here). We can summarise the key functions that nano-engineering confers on these products as packaging and targeting – the active drug molecules need to be protected from the body’s systems for repelling foreign materials, and if possible they need to be actively targetted to the parts of the body at which the therapy is directed. For the anti-cancer therapeutics that dominate this list, this target is the tumour.
One approach to targetting is to wrap the molecule up in a liposome – a nanoscale container that is formed, by self-assembly, when soap-like lipid molecules form a bilayer sheet which folds over on itself to make a bag. These are the same structures that are already incorporated in some cosmetics. DaunoXome® consists of the anti-cancer drug daunorubicin encapsulated in liposomes, and is used for the treatment of HIV–related Kaposi’s sarcoma. Doxil® and Caelyx® are liposomal preparations of the related drug doxorubicin, and are used for advanced ovarian cancers. Simple liposomes have quite a short lifetime in the body; in Doxil the surfaces of the liposome are modified by being coated by the water soluble polymer polyethylene glycol.
Rather than putting the drug in a liposome, and then coating the liposome with polymer, it is possible simply to attach polyethylene glycol directly to the drug. This is the basis of “polymer therapeutics” (this is Ruth Duncan’s own field). Examples in clinical use include Oncaspar®, for acute lymphoblastic leukemia, and Neulasta®, used to decrease infection in patients receiving chemotherapy. Both these drugs consist of a protein drug molecule which is disguised from the body by being coated in a diffuse cloud of polyethylene glycol (PEG). How PEG works is still not entirely clear, but the basis of the effect is that it forms a diffuse layer which resists protein adsorption.
Mylotarg®, a drug licensed in the USA for acute myeloid leukemia, is a (currently rather rare) example of a targetted drug. The drug itself – a potent anti-tumor antibiotic – is chemically linked to an antibody – a protein molecule which specifically binds to chemical groups on the outside of the target cells. In Abraxane™, it is the drug molecule itself, paclitaxel, that is nanoengineered – it is prepared in a nanoparticulate form to improve its solubility; the nanoparticles are coated with the blood protein albumin.
So what we see now are a number of products which use individual tricks of nanoengineering to improve their effectiveness. What we will probably see in the future is the combination of more than one of these functions in a single product – moving beyond clever formulation to integrated nanodevices.
Hello, Richard,
First, I want to thank you for your very kind words regarding my farewell from the blogosphere. It means a great deal to me, especially coming from a scientist.
Now, if you don’t mind me committing an act of public relations, I do want to tell you what a couple of subsidiaries of my new company, Arrowhead, is up to when it comes to drug delivery and fighting cancer.
Insert Therapeutics and Calando Pharmaceuticals are subsidiaries of Arrowhead, and both of these companies are close to human clinical trials.
Insert has a drug delivery system that has achieved complete remission of some tumor types in mice and has shown promise across a wide range of cancers. The innovation here comes from Mark Davis of Caltech, who invented a rationally designed system called Cyclosert. It protects healthy parts of the body against the toxic effects of cancer medication and releases it precisely where it’s needed while producing no immune responses.
“Rational design” is akin to the early vision of nanotechnology, which is to build precisely what you want from the “bottom up.” It means that Dr. Davis is no accidental nanotechnologist performing blind experiments with unknown and untested materials. In other branches of nanotechnology, researchers may discover or create novel materials, then spend years or even decades trying to figure what exactly the new nanoparticle can do and how it could be helpful or harmful to the human body.
Dr. Davis, however, manipulates already-tested materials and uses their known properties, chemistry and interactions as components or functions of more-complex systems. Dr. Davis’ specialty is designing systems to deliver nucleic acids — the basis of Calando’s unique technology.
Get ready for an announcement soon on a new investment into this company, plus partnerships with big pharma firms and, of course, human trials.
Calando uses Cyclosert as a vehicle to deliver RNAi, and it’s worked pretty impressively. Our latest announcement earlier this week is that it effectively “silenced” Ewing’s sarcoma in mouse models. Human trials are next for them, too.
Thanks, Richard. And I’m happy to see the nanotech blogging world is doing just fine without me.
Howard
It’s good to hear from you, Howard. RNAi is undoubtedly a very exciting technology – I wrote about it earlier this summer here. And it is also clear that without some very smart nanotech to deliver these nucleic acids it’s not going to get anywhere – I look forward to hearing more about the Caltech technology in this respect. I’m glad you’ve found out there’s more to academic nanoscience than grinding powders small!