Ultrasound Waves For Transdermal Drug Delivery

An anonymous reader writes with news of research from MIT, where engineers have found a better way to use ultrasound waves to boost the permeability of skin for the delivery of drugs. "Ultrasound — sound waves with frequencies greater than the upper limit of human hearing — can increase skin permeability by lightly wearing away the top layer of the skin, an effect that is transient and pain-free. ... When ultrasound waves travel through a fluid, they create tiny bubbles that move chaotically. Once the bubbles reach a certain size, they become unstable and implode. Surrounding fluid rushes into the empty space, generating high-speed 'microjets' of fluid that create microscopic abrasions on the skin. In this case, the fluid could be water or a liquid containing the drug to be delivered. In recent years, researchers working to enhance transdermal drug delivery have focused on low-frequency ultrasound, because the high-frequency waves don’t have enough energy to make the bubbles pop. However, those systems usually produce abrasions in scattered, random spots across the treated area. In the new study (abstract), the MIT team found that combining high and low frequencies offers better results. The high-frequency ultrasound waves generate additional bubbles, which are popped by the low-frequency waves."

Comments

Does this replace DMSO?

[Anonymous Coward]

Well?

Re:Does this replace DMSO?

[Adriax]

Not really.
"Hold still chummer while my narcojet plays soothing music to your skin." wouldn't go over very well with security on your run.
GM final say of course, maybe the corps decided to gene therapy their citizens with sloth dna or something and it would work...

Already got one.

[ColdWetDog]

Just for a bit of background.

Sonophoresis (or Phonophoresis) is a older technology that sort of works. Hasn't make much in the way of clinical inroads because of a number of problems. This work may overcome some of that although having to go to a physical therapist (typically) to get some drug stuffed in your body is typically more trouble that it's worth.

The most common use for this technique is to push steroids to a localized area (such as along a tendon) instead of giving the drug in a pill and having it diffuse through the entire body or using multiple, painful injections. Sort of works.

Re:Already got one.

[wwphx]

I so hope this becomes a marketed product soon! I do two subcutaneous infusions a week, four needles in my abdomen for about an hour a session and will be doing so for the rest of my life. This would be SO sweet!

Re:Already got one.

[BoRegardless]

What I am interested in is whether the ultrasound modifies the chemicals being transported -- injected???

Ultrasonic bubbles can create implosions that raise temperatures into the range of thousands of degrees farenheit.

Ultrasonics are routinely used to bond plastics as a result of the temperatures induced.

The question comes down to whether you destroy or modify the molecules you want to deliver...however slightly. Needles don't do that.

Re:Already got one.

[jbeaupre]

The summary gets some details very wrong. Intense ultrasound can create cavitation bubbles, but nothing of that intensity is used for drug delivery. It that were to happen, it would kill living cells. So, no bubbles, no implosions, none of that stuff.

At the lower levels used, ultrasound strains the cells, creating small openings between cells and in cell membranes. Skin becomes "leaky."

Re:Already got one.

[TheSwift]

Ultrasounds are routinely used to look at human organ systems to evaluate for disease processes. The technology is extremely well-researched and it is considered significantly safer than CT scans or X-rays since it lacks the radiation and has an apparent lack of risks. The ultrasound isn't being done when the medication is administered to the patient's skin. The transdermal medication would be given after the ultrasound treatment has already removed the top layer of skin, therefore there would be no possibility of "modifying" the medications. I don't think ultrasound waves hide in cells and jump out at the last second when the medication is given. Needles come with many risks including introducing bacterial infection. A transdermal method may be very effective and preferred, especially for pediatric patients or adults who have anxiety about needles. If this was marketed at a consumer level one day, it could mean that diabetic patients wouldn't have to poke themselves on a daily basis anymore - which I imagine would be very desirable by millions of people. This tech is worth looking into.

Re:Already got one.

[Paul Fernhout]

"If this was marketed at a consumer level one day, it could mean that diabetic patients wouldn't have to poke themselves on a daily basis anymore"

Or most Type-2 diabetics could just eat more vegetables and get enough vitamin D: :-)
http://www.drfuhrman.com/disease/Diabetes.aspx
http://www.vitamindcouncil.org/health-conditions/diabetes-and-endocrine-diseases/diabetes-type-2/

And pregnant women and infants could get enought vitamin D and may prevent Type-1 cases:
http://www.vitamindcouncil.org/health-conditions/diabetes-and-endocrine-diseases/diabetes-type-1/

I agree with you about the risks of needles though (including to medical staff who work around sharps and could accidentally get stuck by one and get a disease like AIDS). However, ultrasound may have its own risks, too. Have you ever run a stream of water into a sink and had one drop bounce out of the sink from some weird interaction of waves giving some small amount of water a much higher velocity than the total stream? Waves can interact "constructively" in odd ways in relation to resonance and other concepts.
http://en.wikipedia.org/wiki/Interference_(wave_propagation)
http://en.wikipedia.org/wiki/Tacoma_Narrows_Bridge_(1940)

Whenever you inject macroscale energy into a system, whatever the form (heat, light, sound, etc.), you run the risk of resonance effects or other effects causing microscale damage. As another example, heat up the planet Earth, and you may get more hurricanes that rip the roofs off homes.

It's a question of risk vs. reward and for whom. Something does not have to be perfect to be better. The important thing is to fully understand the various tradeoffs and make informed decisions. It may well be that any risks from ultrasonic transdermal delivery of drugs may outweigh any risks relative to other options. Although, I'd still suggest eating better and having a healthier lifestyle and so on is, in general, better than taking drugs to paper cover up the symptoms of vegetable deficiency disease and sunlight deficiency disease. Like Dr. Joel Fuhrman says, a typical prescription is taken by most people as a "permission slip" to keep eating poorly or doing other problematical lifestyle things.

Re:Already got one.

[TheSwift]

I think I'm understanding your point more and your concerns in your other comment make a little bit more sense. You're right in saying that there is a lot of potential for harm in technology before we're fully aware of it's implications and there are plenty of historical examples of that. However, it doesn't mean we shouldn't explore technologies that could be extremely effective. It just means we should proceed with caution. If that's your point, then I agree. Researchers should give careful thought to what they're dealing with. Of course diet and exercise is necessary to helping diabetics. Vitamin D may have quite a bit of potential as your sources indicate. However, I do know that without sufficient insulin diabetics can quickly recede into DKA and die. If Vitamin D and other means of treating it can help wean them off of it, fantastic, but in the meantime, diabetics need to take the right medication (insulin in many cases) until they can make the necessary lifestyle changes.

Yeah!

[Anonymous Coward]

Science is fucking awesome.

Hypospray

[yincrash]

Woooooo. Sci-Fi gone real! Please tell me it makes the same sound too.

Re:Hypospray

[preaction]

We've had the hypospray for some time, it's just not good for everyday use. http://en.wikipedia.org/wiki/Jet_injector

Re:Hypospray

[another random user]

How about laser injection - http://www.bbc.com/news/technology-19600706

Above page links through to:
Er:YAG laser pulse for small-dose splashback-free microjet transdermal drug delivery - http://www.opticsinfobase.org/ol/abstract.cfm?uri=ol-37-18-3894

Re:Hypospray

[RoxyFlox]

Like maybe finding a way to avoid needing to sterilise it between uses? I can't seem to find any footage from Star Trek where a doctor or nurse cleans one between uses, sometimes even swapping one cartridge of medicine for another, which usually causes mixing of any residual fluids.

Just guessing . . .

[reboot246]

I'd bet this method wouldn't work for dogs.

Re:Just guessing . . .

[Anonymous Coward]

It would on my peruvian hairless

This is great!

[RoxyFlox]

This would surely be a godsend to anyone with a phobia of sharp objects, like hypodermic needles.

Question for the med community

[AnotherAnonymousUser]

I realize Google is my friend in this, but I'd love to hear from insider perspective what sort of advances are actually *in use* in clinics and hospitals these days. About 10-15 years ago I used to read in Pop Sci about the innovations in needle technology - serrating the edge like a mosquito, using thinner needles, new kinds of shots, and using these painless, efficient methods of delivering vaccines and medicine. What of those actually panned out? It's been about 10 years since I've received a vaccination; did any of those technologies we read about 10 years ago make it into the field?

Re:Question for the med community

[Anonymous Coward]

Short answer: no. I had to get a tetanus shot a year ago and I was at a pretty damn nice facility when they administered it with a normal needle.

(maybe you have to be rich or something to get the super stuff).

Re:Question for the med community

[Anonymous Coward]

From the insurance perspective, your suffering is cheaper than newer tech.

Re:Question for the med community

[dunkelfalke]

Nope, still standard stuff.
By the way, if it has been 10 years, it is now time to do the next booster (diphteria/tetanus/pertussis if in USA, add polio for Europe).

Re:Question for the med community

[TheSwift]

I'm a pre-med student and I work for physicians in an emergency department. I've seen several pretty nifty innovations for administering IV's. In pediatric hospitals, they often use air-pressure needle-free methods of starting IV's and administering medications. To be honest, I'm not sure how they work, but they do exist and instead of having a metallic needle in your arm, it is tough, but malleable plastic. They aren't generally used mainstream in most hospitals yet, especially not in the ER. My guess is that they are more expensive and it may be more difficult to start IV access to an adult vein using needle-free technology. Some benefits though, are a reduction in introducing bacteria to a bloodstream (no potentially contaminated needles) reducing the "scare factor" from having a needle shoved in your arm. One of my close friends is a cancer survivor and he had the technology used on him many times and he said it hurts a helluva lot less than needles. http://www.icumed.com/products/infusion-therapy/needlefree-vascular-access-devices.aspx BTW, thinning needles isn't always helpful, especially if you want to administer drugs quickly (critical care situations).

What about Lasers?

[Anonymous Coward]

I am a bit more interested in the new Laser Injected method developer in South Korea.

This is good

[Anonymous Coward]

I read a few weeks ago that a group trying to kill cancer mated an ultrasound machine with an MRI. They targeted the cancer with the MRI, and blasted it (in 3 dimensions) with the ultrasound. Ultrasound makes cancer tumors 'fragile'. They are far more prone and are profoundly more affected by chemotherapy than they would be otherwise. What do I mean by that? Normally after 6 weeks of chemotherapy, a tumor might shrink by 30%. After the MRI/ultrasound and a single dose of chemotherapy, the tumor might shrink by 50% (in rough and general terms, they did multiple tests on multiple patients and these are generated averages). Its like 'it just isn't for the epidermis, but can be used to make the cancer tumor 'skin' more prone and able to absorb the chemo coctail more easily, making the treatment more effective, leaving less chemo cocktail in the rest of the body, meaning the tumor suffers the worst, and surrounding tissue is affected less.

he's dead Jim

[indybob]

Sound like the StarTrek HipoSpray... http://www.ffesp.com/portal/images/stories/Articles/Noticias/fotos_2012/Hipospray.jpg

Free Radicals

[the eric conspiracy]

I'd be kinda leery of this one. It's long been known that ultrasound in liquids can lead to the formation of free radicals. I'd think that this could potentially lead to a variety of nasty side effects including DNA damage.

Maybe even radiation, too?

[Paul Fernhout]

http://en.wikipedia.org/wiki/Bubble_fusion
http://peswiki.com/index.php/Directory:Cavitation
http://www.articlesextra.com/cavitation-fusion-nuclear.htm
http://nextbigfuture.com/2012/06/brillouin-funded-for-2-million-and.html

Re:Maybe even radiation, too?

[TheSwift]

Do a control-F search for "radiation" on any of those articles listed. You will find 0 results. Ultrasound technology has zero radiation. It uses sound waves at frequencies relative to its preferred use. It is used frequently in hospitals every day and it is actually done to AVOID radiation caused by CT scans and X-rays.

Re:What about this one?

[miknix]

There is a research team which came up with something similar (I think), their product should be in the markets next year already:
"A laser syringe being developed in Portugal should be on the market within a year":
http://www.innovationtoronto.com/2012/07/needleless-syringe-invention-on-market-within-a-year/

I don't understand much about it but it looks like both ideas (ultrasound and laser) use the same technique (changing skin permiability) to deliver the payload.

Ha! Good luck with that.

[Sensei_knight]

Will this become vaporware like the ultrasound technology to remineralize tooth structures that came out from U of Alberta at Edmonton about a decade ago? Ultrasound mayby be a major yet under-realized(suppressed?) discipline of physical molecular creation, or in this case destruction. I'm not going to hold my breath, not even for one or two peer reproduced small mammal studies.

Re:Ha! Good luck with that.

[Anonymous Coward]

The one thing new, at least to me, is the idea of using two different frequencies. Other than that, cavitation was not mentioned in the article linked to by the op, but many above have talked about it. Did anyone use the term 'acoustic streaming?'

Also interesting is the question of why and how new technologies, or simple techniques, get adopted into standard practice or fall by the wayside. I'm sure this a complicated subject, worthy of a graduate thesis or a conspiracy.

My two favorite examples: a spray of xylocaine or novacaine into the sinuses reduced migraines or aborted them if taken at the onset. Heard it 10 or so years ago (Dr Dean Edel on the radio during a gee whiz moment?), a little blip on Wikipedia but nothing else.
#2. varicose veins are thought to be 'unresponse' to treatment; they don't get better. An Article in Lancet 20 some year ago tested a treated: 3 days on a slant with your legs raised above you heart. This reversed gravitational effects on lower limb circulation. 3 days means no bathroom breaks, use a bedpan. The idea was to give a rest to the veins from gravity. Some level of improvement was reported. Of course, how much does the surgeon not make by that treatment?

Bubble fusion from ultrasonic waves

[Paul Fernhout]

Sorry, but you and whoever modded that post down missed the point. There is an apparent affect where imploding small bubbles in liquid can cause nuclear fusion or some similar process involving very hot temperatures like the surface of the sun and so possibly emit radiation as evidenced by the production of light (although the details remain controversial). Ultrasonic sound waves can apparently cause such small bubbles, and so the proposed idea of injecting drugs using ultrasonic waves to cause small bubble may be a potential radiation risk. From the wikipedia link:
http://en.wikipedia.org/wiki/Bubble_fusion
"Bubble fusion, also known as sonofusion, is the non-technical name for a nuclear fusion reaction hypothesized to occur during a high-pressure version of sonoluminescence, an extreme form of acoustic cavitation.[1] The mechanism of sonofusion was proposed in 2002 by Rusi Taleyarkhan. Experiments in following years have produced conflicting results about whether it is possible to cause a fusion reaction with this method."

Emphasis being on "nuclear fusion".
http://en.wikipedia.org/wiki/Sonoluminescence#Nuclear_reactions

And this supports the original poster's point about free radical damage. Maybe free radicals are caused by radiation from the imploding bubbles?

If you want to learn more about bubbles and possible radiation, watch this youtube video about snapping "Pistol Shrimp", who use the effect to stun prey:
http://www.youtube.com/watch?v=DeFUO2F7Gvw

So the question is, could this be happening in this attempt to inject medicine via ultrasonics? Compare what is quoted above from Wikipeida with this part of the summary of the original article: "When ultrasound waves travel through a fluid, they create tiny bubbles that move chaotically. Once the bubbles reach a certain size, they become unstable and implode. Surrounding fluid rushes into the empty space, generating high-speed 'microjets' of fluid that create microscopic abrasions on the skin."

Imploding bubbles are referenced in both.

Of course, many mainstream physicists may find this idea of bubble fusion heretical, same as they object to the idea that nuclear processes can go on at the surface of a metal lattice (or maybe inside one):
http://pesn.com/2012/09/06/9602177_LENR-to-Market_Weekly_September6/
http://hardware.slashdot.org/story/07/05/11/184239/bubble-fusion-researcher-faces-fraud-trial
http://science.slashdot.org/story/04/04/19/1117201/bubble-fusion-results-replicated-by-4-institutions?sdsrc=rel

Am I saying typical ultrasounds used for diagnostic imaging produce this sonofusion effect? No. Although now that you bring the issue up, maybe they can?

By the way, as far as ultrasound and the developing human brain and ear related to ultrasounds performed during pregnancy, even without radiation issues, consider:
"Prenatal exposure to ultrasound waves impacts neuronal migration in mice"
http://www.pnas.org/content/103/34/12903.full

What are the implications?
http://www.naturalchild.org/research/yale_ultrasound.html
"Physicians should continue to be prudent about the use of ultrasound and perform the study only when medically necessary and when benefits outweigh risk, according to the American College of Radiology. The advice comes in the wake of recent findings by Yale researchers that link prenatal ultrasound exposure to brain damage."