Here are two references which directly answer your question. Look at their summarized tables:

1. McNeil et al. Nature Nanotech 2007

http://bdds.fudan.edu.cn/picture/article/111/4b/4c/95e5ee2948c491dc24c7604ff127/fdfa2aa9-df2b-4c9f-a2a5-a33ee29acb76.pdf

2. Davis et al. Nature Reviews Drug Discovery 2008

http://www.nature.com/nrd/journal/v7/n9/pdf/nrd2614.pdf

I know of ferridex which is used as an MRI contrast agent. I also know of doxil and paclitaxel which are anti-cancer drugs. Please share if you know of others. Giving the references will be even more helpful.

You don't strictly mean drugs, then, but any therapeutic/diagnostic particles?

There are a number of contrast agents (gadolinium, iron oxide).

There is at least one iron oxide particle approved for hyperthermic treatment of tumours.

There are also iron oxide particles used to treat anaemia.

I'm not familiar with nanoparticles used in the clinic for drug delivery.

If your interest is the nature of the diseases diagnosed/treated using nanoparticles, then you'll be looking at a broad spectrum of conditions: cancer, anaemia, and potentially any condition that can be treated with any drug.

Stuart and Shubhadeep,

Thank you for your responses. I appreciate it.

Yes, I am interested in the medical applications of nanoparticles especially those which are already in the market or undergoing clinical trials. If you could refer useful recent articles that will even be better.

Here are two references which directly answer your question. Look at their summarized tables:

1. McNeil et al. Nature Nanotech 2007

http://bdds.fudan.edu.cn/picture/article/111/4b/4c/95e5ee2948c491dc24c7604ff127/fdfa2aa9-df2b-4c9f-a2a5-a33ee29acb76.pdf

2. Davis et al. Nature Reviews Drug Discovery 2008

http://www.nature.com/nrd/journal/v7/n9/pdf/nrd2614.pdf

Leo,

Thank you very much. This is very helpful!

From my PhD:

"Of the MPs reported in the literature, those incorporating iron oxide (typically either magnetite or maghemite) have a good safety profile, and some formulations have been approved for clinical applications [e.g. EndoremTM, Resovist® and SineremTM, as MRI contrast agents;148,181 NanoTherm® for hyperthermic tumour therapy;97 ferumoxytol (Feraheme®) for iron-deficiency anaemia182],..."

97. Taylor, A., Wilson, K. M., Murray, P., Fernig, D. G. & Lévy, R. Long-term tracking of cells using inorganic nanoparticles as contrast agents: are we there yet? Chem. Soc. Rev. 41, 2707–2717 (2012).

148. Wang, Y. X., Hussain, S. M. & Krestin, G. P. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur. Radiol. 11, 2319–2331 (2001).

181. Schäfer, R. et al. Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles. BMC Cell Biol. 11, 22 (2010).

182. MacDougall, I. C. Evolution of IV iron compounds over the last century. J. Ren. Care 35, 8–13 (2009).

Hi Stuart,

This is awesome. Thank you for providing the 2012 and 2010 references. I know of the ferumoxytol, Resovist and Sinerem (was discontinued). I also know of Ferridex but when searching for it, I found that is was taken out of the market because of side effects. Combidex is another iron oxide based MRI contrast agent that also was discontinued. I am confident that nanomaterials with medical values are out there either already approved or undergoing clinical trials for approval.

I can provide a few more examples in case you were interested in therapies where the drug had passed all regulatory scrutiny. In the following examples, the nanoparticles consist of the drug itself. All the following are marked products.

Rapamune (Pfizer) an immunosuppressant; Emend (Merck) an antiemetic; Megace ES (Par) treats apetite loss; TriCor (Abbot) cholesterol and triglyceride lowering; Invega Sustenna (Janssen) an antipsychotic drug. The first 4 are oral dosage forms and the last an IM depot. These drugs were manufactured under license using Elan’s NanoCrystal technology (now a part of Alkermes).

Shubhadeep and Niels,

Thank you very much for all your answers. These are all very helpful for me. If you can point me to the references about these diagnostic and therapeutic NPs, that will be even more helpful. I am interested in all forma of diagnostic and therapeutic NPs.

Niels in your examples when you say the therapeutic is a nanoparticle of the drug it self, do you mean that Elan's NanoCrystal technology makes nanometre sized crystals of the drugs and administer that?

Yes, that is correct. A wet milling technique is used to reduce particle size of the crystalline drug (together with stabilizers). The term nanoparticle or NanoCrystal was used prior do the FDA and EU definitions and encompasses larger sizes than 100 nm (typically up to 400 nm).

I should perhaps clarify a little bit. The active ingredient is typically milled to 100 -400 nm size, which produces a suspension product intermediate. This can be further processed into solid dosage forms like tablets and capsules. The formulation challenge is to make a presentation that ensures more or less complete redispersibility. Rapamune and TriCor are tablets, Emend is a capsule, Megace ES is an oral suspension, and Invega Sustenna is an injectable suspension.

Niels, does this mean that the individual drug particles are in the nano dimensions but are compacted into tablet or capsule form? How about the suspension and the injectible forms?

Zoraida, probably it might regards to your question also. SunStone introduced a series of commercially available (by Sigma-Aldrich) upconverting nanocrystals for immunohistochemical and immunocytochemical diagnosis and bioimaging: http://www.sigmaaldrich.com/china-mainland/zh/technical-documents/articles/biology/upconverting-ucp-nanocrystals.html

here I had attach a pdf in which there are some example of nanoparticle based drug. so find it

Hi Anna and Abishek, Thank you so much. These are all very helpful leads.

Zoraida, yes the drug particles are in the nanosize as defined earlier. Tablets and capsules made from NanoCrystal Dispersions contain the nanoparticles embedded in an excipient matrix. Upon ingestion, the tablet/capsule disintegrates which is followed by redispersion of the nanoparticles. The redispersion is a part of the formulation development efforts. For suspension products, these are usually “as is”, possibly with a preservative added. They may also be diluted into a concentration that makes the dosing volume easy to achieve. Injectable dispersions are terminally sterilized or produced aseptically.

It looks to me that all these "nano-drugs" are nothing more than suspensions of finely milled solids. The "justification" for calling it "nano-particles" is simply that their dimension/diameter is expresed in nanometers. For particles of e.g., 400 nm, one could easily express it as 0.4 um, and call it a micro-particle. So what is new?

Some refers to the milling approach as a low tech approach to nanomaterials (e.g. top down rather than bottom up). The results, however, may be extraordinary at times. Such milled drug suspensions often show an increased bioavailability, earlier onset of action and usually reduced fed/fasted variability. Like nanomaterials in the purest definition, the size influences the extent of the benefits (i.e. a tunable property). Milling by itself is simple, to make a stable dispersion is not so simple, and to make a tablet that disintegrates in to its primary particle size is far from trivial.

There are different types of nanomaterials. There are, for example, gold nanoparticle with ligands attached that are intended to target tumor sites. There are hollow sphere materials with nanosized openings to control the release rate. The ones I happen to have mentioned are finely milled drug particles.

The FDA and EU regulators have defined nanomaterials as materials with one or more dimension in the 1 – 100 nm range (without any mention of how these are made). Before that, it was common practice to refer submicron materials as nanomaterials (e.g. R. Mueller, and others).Elan’s definition happened to be somewhere in between. Ultimately, it is about the benefit that the size brings with it matters.

You mentioned "nanoparticles with ligands attached that are intended to target tumor sites" and "hollow sphere materials with nanosized openings to control the release rate". Nanoparticles has as yet contributed nothing new to the efficacy of advanced/site-specific drug targeting. Reason? The task is far too complex to be accomplished by size alone... Size may be a necessary but definitely not a sufficient feature...

Hi Niels,

Thank you for the very informative and well written response. I agree with all that you mentioned.

We have worked with nanomaterials that are used to load drug by attachment on the surface and by loading the drug inside the hallow hydrophobic layer. And yes, these are still in the in vitro and pre-clinical stage so no one has benefitted from them yet. These nanomaterials range from 2 to 100 nm so these are really very small.

Hi Karel,

Thank you for your answer and participation. I greatly appreciate it.

There is a lot of new stuff going on in the nanomaterials for drug delivery right now. A lot of them are not in the publications yet but these are on-going. Also, the use of nanomaterials for targeting is very new. It is the second stage of nanomaterial mediated drug delivery and is still undergoing the drug-loading and drug-targeting stage. A few are in pre-clinical and clinical trials but are not published it.

Be patient with nanotechnology, which is the technology of this century. Watch out what happens to it in the various fields of its applications as the years go by in the same way that we watched what happened to the semi-conductor industry and the biotech industry in the last century. These technologies did not bloom overnight, it took them years before the fruits were harvested. Look at the IC chips now and compare them to those in the 1970's or even way back before that. Look at th genome project now. Similarly, I believe, it is just a matter of time when one of our diligent researchers will come out and tell the world that the nanomaterial-targeted drug delivery is the best cure for one incurable disease. Once that first breakthrough happens, the rest will follow in due time.

Your sentiments may all be justified, but the key point is that "drug delivery" considerations need to start with the drug - it is the pharmacokinetics and pharmacodynamics of the drug that is to be "manipulated". technological development that starts with developing "materials" such as "nanoparticles" (or any other drug vehicles for that matter) without full considerations of the basic requirements and principles that all need to be met is likely to (as it has been for some 50 years now) result in failure. Looking for a drug vehicle that is a generic "Trojan horse" is futile in my view.

My suggestion - select a drug, or at least a class of drugs, determine what drug behaviour you seek to achieve, and then develop your plans accordingly.

Karel,

You seem to be missing the points all together.

The drugs are already out there and are FDA approved. What do you think doxorubicin is for?paclitaxel? camptothecin? and many many more?

The behaviors of the drugs being used as they are right now without nanomaterials as delivery vectors are already known to the sponsors, pharmaceuticals, the FDA, EMA, and other agencies worldwide. But, the drugs have unwanted characteristics that the use of nanomaterials as carriers may be able to solve.

Please read the book "Nanomaterials for Medical Applications" . If you don't have it yet, please request your library to get it. It is a very good resource/reference book for the various uses of nanomaterials in medicine.

Talking of "missing points", there is one you need to consider.

Should your nanoparticle deliver e.g., doxorubicin close to the intended target, e.g., to the cell surface and the drug is released there, the overall rate of drug delivery and release would need to be higher than the rate of drug escape from the site for the drug delivery system having at least a chance of being more effective than the drug alone.

Please, show me the actual clinical data demonstrating that nanoparticle delivery has improved clinical efficacy of doxorubicin or a similar drug. Cheers.

As I previously mentioned above, there is a lot of new stuff going on in the nanomaterials for drug delivery right now. A lot of them are not in the publications yet but these are on-going.

The use of nanomaterials for targeting is very new, it probably started during the past 5 years or so. It is the second stage of nanomaterial mediated drug delivery and is still undergoing the drug-loading and drug-targeting stage. A few are in pre-clinical and clinical trials but are not published and I doubt that these will be published for public consumption because pharmaceuticals do not release their information to the public except to the FDA, EMA, and other regulatory agency.

You can find more explanation of the points I am making at: Karel Petrak, Targeted Drug Delivery––Quo Vadis? Article first published online: 29 DEC 2011, DOI: 10.1002/ddr.20492, © 2011 Wiley Periodicals, Inc., Issue: Drug Development Research Volume 73, Issue 2, pages 59–65, March 2012.

Karel,

Will you send me an electronic copy of your papers you mentioned?

Zoraida,

My wife is an expert in the field of Photodynamic Therapy and she advices You to check PDT - there are numerous efforts to use directly nanoparticles as photosensitizers and also nanocarriers, including polymer micelles and liposomes. The best to our knowledge, clinical trials should be ongoing in Canada, USA and Scandinavian Countries.

Wojciech,

Would you (or your wife) be able to elaborate on the clinical uses of PDT, specifically what role/niche they serve to fill in the treatment of specific diseases?

Hi Wojcieh,

Thank you for the advice. Does she have any publications she can share? That will be very helpful to follow and check out.

Review Article

Nanomedicine

Betty Y.S. Kim, M.D., Ph.D., James T. Rutka, M.D., Ph.D., and Warren C.W. Chan, Ph.D.

N Engl J Med 2010; 363:2434-2443December 16, 2010DOI: 10.1056/NEJMra0912273

Do a literature search for the following that are in clinical trials:

BIND-014, CALAA-01, MBP-426, SGT-53.

Hi Fatih,

This review is helpful. I appreciate you adding it to this page. Thank you very much for your participation and input.

Perhaps this review could be useful for you:

Nanoparticle delivery systems for cancer therapy: advances in clinical

and preclinical research

Clin Transl Oncol (2012) 14:83-93

DOI 10.1007/s12094-012-0766-6

Hi Rosa,

Thank you so much. I appreciate it. Do you have the names of he authors?

These are:

Susana Patricia Egusquiaguirre · Manuela Igartua · Rosa María Hernández · José Luis Pedraz

It would depend on how you define a "nano-particle". Since drugs act at a molecular level, and each molecule of any drug is a nanoparticle, one might consider all drugs on the market to be in a form of "nano-particles".

In addition to Rosa's excellent article I was just reading another good review on nanoparticle applications in clinic; as drug delivery systems in oncology. From the world of Robert Langer and co: Annu. Rev. Med. 2012. 63:185–98.

Michael, thank you for including this reference in your reply. This is helpful.

On of possible directions is treatment of arthritis, e.g. in paper:

Article Effect of Gold Nanoparticles in the Treatment of Established...

What specific advantages did nanoparticles offer in case of the quoted drugs (i.e., Rapamune, Emend, Megace ES, TriCor, and Sustenna) over other/conventional formulations?

Improved bioavailability, reduced fed fasted variability, dose proportionality.

Can you quantify your answers, please?

Niels, can you elucidate further on the drugs you mentioned? RAPA is an immunosuppressive drug but is it nanoparticle mediated or is it manufactured in nanoparticle size? Are EMEND, Megace Es, Sustenna and Tri Cor nanoparticle mediated or are they manufactured in nanoparticel size?

You may find some in the review paper of R. Duncan:

dx.doi.org/10.1021/mp200394t | Mol. Pharmaceutics 2011, 8, 2101–2141

Or in the review of Petros/de Simone:

NATURE REVIEwS | Drug Discovery VOLUmE 9 | AUGUST 2010 | 615

A list of "marketed nanomedicine products" is readily available at http://www.nature.com/nbt/journal/v24/n10/fig_tab/nbt1006-1211_T2.html .

There you will find out that these products are mainly lipid and micellar formulations, vaccines, and dental-repair materials. Basically the only "new" thing is that they are now called "nano" materials... What's in the name?! I do not believe that giving a problem a new name solves anything.

http://www.sciencedirect.com/science/article/pii/S0006295212000330

There is an extensive list at

https://en.wikipedia.org/wiki/Nanomedicine#Applications_and_reported_research_studies

Nanomedicine(s) under the Microscope

Ruth Duncan, and Rogerio Gaspar

This version was generated on Wednesday, 1st June 2011

http://www.ruthduncan.co.uk/#/2011-nanomedicines-review/4551969069