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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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April 12, 2013

Nano-Drugs: Peaked, Or Maybe Past

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Posted by Derek

Nano-everything has been the rule for several years now, to judge from press releases and poster abstracts. But here's an article in Nature Reviews Drug Discovery that's wondering what, exactly, "nanomedicine" has offered so far:

. . .Indeed, by some quantitative measures, the field is flourishing; over the past decade there has been an explosive growth in associated publications, patents, clinical trials and industry activity. For example, a search of the worldwide patent literature using 'nanoparticle and drug' resulted in over 30,000 hits. . .

New biomedical technologies have often undergone a similar life cycle. Initially, exciting pioneering studies result in a huge surge of enthusiasm in academia and in the commercial arena. Then, some of the problems and limitations inherent in the technology emerge, the initial enthusiasm is deflated, and many players leave the field. A few enthusiasts persist and eventually the technology finds its appropriate place in research as well as in clinical and commercial applications. It seems possible that nanomedicine is now verging on the phase of disillusionment.

That's exactly the cycle, and what's never clear is how steep the peaks and valleys are. Some of those deflationary cycles go so deep as to take out the entire field (which may or may not be rediscovered years later). That's not going to happen with nanoparticle drug delivery, but it's certainly not going to make everyone rich overnight. As the article goes on to detail, these formulations are expensive to make (and have tricky quality control issues), and they're not magic bullets for drug delivery across membranes, either. So far, the record of the ones that have made it to market is mixed:

. . .Addressing these challenges would be strongly justified if major benefits were to accrue to patients. But is this happening? Although we do not know the potential benefits of the nanomedicines currently under development, we can examine the early-generation nanoparticle drugs that entered the clinic in the 1990s and 2000s, such as the liposomal agents Doxil and Ambisome and the protein–drug nanocomplex Abraxane. These agents are far more costly than their parent drugs (doxorubicin, amphotericin B and paclitaxel, respectively). Furthermore, these nanomedicines made their mark in the clinic primarily by reducing toxicity rather than improving efficacy. . .

The big question is whether these toxicity reductions warrant the increased prices, and the answer isn't always obvious. The current generation of nanoformulations are different beasts, in many cases, and it's too early to say how they'll work out in the real world. But if you Google the words "drug nanoparticles revolution", you get page after page of stuff, and clearly not all of it is going to perform as hoped. Funding seems to be cresting (or have crested) for this sort of thing for now, and I think that the whole field will have to prove itself some more before it climbs back up again.

Comments (16) + TrackBacks (0) | Category: Pharmacokinetics


1. Marcos Sainz on April 12, 2013 11:49 AM writes...


I'm a long-time reader/first-time commenter. This is off-topic, but I sent a PM to your gmail account last week that may have found its way to the recycle bin. I have since resent the message, and any correspondence would be greatly appreciated. Keep up the great work!

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2. Anon on April 12, 2013 12:11 PM writes...

If you are ever in a medium where you need to interview someone on the topic I would heavily suggest Mauro Ferrari down at Methodist Hospital.

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3. Chrispy on April 12, 2013 12:16 PM writes...

I think "nano" went from having some meaning to being just a buzzword prefix. How is abrazane a "nano" anything? It is paclitaxel bound to albumin. Are antibody-drug conjugates nanomedicines, too?

Does anyone else cringe a little when they hear "nano-" whatever?

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4. blueman on April 12, 2013 12:31 PM writes...

Off topic too - but as you haven't bitten on the electroceuticals yet Derek. Maybe nanoelectroceuticals will be the next wave.

I see GSK have some well formed plans in the area and are prepared to richly reward the community to build those plans

GlaxoSmithKline Electroceutical Ideation Challenge

Bioelectronic medicines or "electroceuticals" promise to treat disease by modulating neural electrical impulses. Which specific disease has a major peripheral neural control component and would be the best proof of principle for such medicines?

You do not need to perform any experiments, only to describe the conceptual approach and need in a total of 3 pages!

Challenge 9933143
Deadline: May 11, 2013
Reward: $5,000

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5. ClutchChemist on April 12, 2013 2:05 PM writes...

Great example of the beginning of a "hype cycle," Derek. I think nanostuffs may have reached the "peak of inflated expectations" point of the cycle. (see graphic for detals:

PEM fuel cells are another example, and one that has already peaked and continued onto the "trough of disillusionment." In the early 90's, every car and house was going to be run on a H2 fuel cell within 20 years. oops.

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6. Matthew Herper on April 12, 2013 2:46 PM writes...

To be fair, doesn't the recent data with Abraxane in advanced pancreatic cancer show that it does have some increased efficacy as well? Up until now, I'd agree there hadn't been tests that proved it did anything but improve side effects. But I'm not so sure we can say that now.

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7. Anon on April 12, 2013 4:10 PM writes...

The point was that Abraxane is no more nano then anything else. The nano appendage has become a vacuous term.

I think we can do better than nano and should go smaller. Let's make pico scaled drugs. Oh wait...

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8. Rudy Juliano on April 12, 2013 4:35 PM writes...


I hope the NRDD commentary didn't come across as too negative. I really do believe there is an important future for nanomedicine. However, as some of the other commentators have pointed out there is also a certain amount of 'hype' and inflated claims in the field. It needs a more balanced approach.


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9. Angie on April 12, 2013 4:35 PM writes...

I cringe when I hear nano too

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10. Anchor on April 13, 2013 4:59 AM writes...

This field is milked to the point that there is nothing else coming out. I am reminded of those days when the combinatorial chemistry gained its currency only to face fast retreat. I believe that these fields will be active at least to keep those specialty journal still in circulation. Two questions...does NIH still keeps funding projects in these area? What will happens to the journals if the rate of progress in this area comes down to a trickle?

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11. Jill on April 13, 2013 6:36 AM writes...

As scientists, we have abused the prefix "nano" in trying to sell one's work, and I agree, I hope that trend is on its way out.
But nano represents a fascinating length scale (the 1-100 nm length scale specifically), where phenomena that we (scientists, engineers, society as a whole) want to emulate occur (e.g. bio), and processes we want to understand and use, begin to arise (e.g. LSPRs).
If hearing the word "nano" is a visceral and negative experience for you, or you think “nano is over,” I hope it’s the abuse of the term that elicits the response, and not the real science that occurs there. How can anyone hate or want to stop researching a frontier where new, perspective-altering phenomena are observed regularly?

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12. David Young MD on April 13, 2013 3:19 PM writes...

It sounds like the idea has peaked and is now fading. This happened with the Liposomal drugs in the late 1990's. Doxil came out as a drug that had a therapeutic advantage over Doxorubicin, but I think that it primarily is an advantage in terms to less side effects, or at least different side effects. Back in 1998 I thought that oncology would see 5 or 6 liposomal new drugs come out over the next 10 years, but none did. And once Doxil was FDA approved, there was no further research on how to make Doxil an even better drug. For a while, in the early to mid 2000's there was much research on liposomal Lurtotecan, but nothing ever came of it.

The same has happened with the albumin conjugated drugs such as Abraxane. In the two or three years after Abraxane was FDA approved, I saw posters at the AACR conference on other anticancer drugs attached to albumin nanoparticles in a similar fashion studies in vitro. But nothing came of them in vivo and they faded after a couple of years. The research on the principle seemed to have stopped. Yes, Abraxsis tried to make something of nanoparticle Docetaxel but it must have failed for I hear nothing of it now.

Abraxane has some advantages over straight Paclitaxel, mostly in terms of less side effects, but not a lot of advantages. One can't help but be disappointed in both of these instances. It is like the principle has failed and the only outcome is a little less side effects.

Abraxane is now owned by Celgene and Medicare has made Patrick Soon-Shiong the "richest man in Los Angeles" having his company bought out by Celgene. So, if liposomal drugs and nanoparticle drugs are so good, why aren't there any more in the pipeline?

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13. Oldnuke on April 13, 2013 9:05 PM writes...

When I hear two nano's, I think of Robin Williams' character Mork --

Mork's greeting was "Na-Nu Na-Nu" (pronounced "nah-noo nah-noo") along with a hand gesture similar to Mr. Spock's Vulcan salute from Star Trek combined with a handshake.

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14. weirdo on April 14, 2013 8:10 PM writes...

My assumption is that "nano" has now peaked, since we already have the next wave of overhypeness: epigenetics.

Get on the train, or get left at the station!!!!!!!!

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15. Vincent on April 16, 2013 4:06 AM writes...

Re. Abraxane being "nano" or not.. it could be a matter of self-assembly of several complexes into small particles (like surfactants), which would make the moniker not too usurped.
But yes, I think "nano" was hyped too much, as if it would be game changer when it's only a group of methods... A difficult one on top of that, that frustrated (and still frustrates) a lot of scientists that delved into it without any formation (i.e. no, a PhD in organic chemistry doesn't give good insights in physical chemistry)

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16. Joseph on August 15, 2013 7:31 AM writes...

I emphatically disagree. Nanodrugs haven't even yet started. Their best utility would be in "cyborg" drugs where necessary functional groups would be attached onto a "nanite" capable of performing real-time "transformer" motion.

Think of being able to move functional groups in space in such a way their 3D molecular geometry permits the necessary bits to dock into a receptor.

If one were clever enough, such devices could be used to gain selectivity of one receptor over another; and even more... to use the same cyborg nanite for two different therapeutic indications via drastic changes in molecular geometry.

The limit is the imagination here.

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