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  10/2/2014Getting (drugs) under your skin | MIT Newshttp://newsoffice.mit.edu/2012/ultrasound-waves-and-drug-delivery-09141/3 RELATED Paper: Rapid skin permeabilization by thesimultaneous application of dual-frequency,high-intensity ultrasound Langer LaboratoryDaniel BlankschteinDepartment of Chemical EngineeringDavid H. Koch Institute for Integrative CancerResearch Getting (drugs) under your skin Using ultrasound waves, researchers boost skin’s permeability to drugs. Ultrasound waves of two differentfrequencies generate tiny bubbles ofwater on the skin’s surface. When thesebubbles pop, the skin’s surface is lightlyworn away, allowing drugs to passthrough the skin more easily. Graphic: Carl Schoellhammer Using ultrasound waves, MIT engineers have found a way to enhance the permeability of skinto drugs, making transdermal drug delivery more efficient. This technology could pave theway for noninvasive drug delivery or needle-free vaccinations, according to the researchers.“This could be used for topical drugs such as steroids — cortisol, for example — systemicdrugs and proteins such as insulin, as well as antigens for vaccination, among many otherthings,” says Carl Schoellhammer, an MIT graduate student in chemical engineering and oneof the lead authors of a recent paper on the new system.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 thatis transient and pain-free.In a paper appearing in the Journal of Controlled Release , the research team found thatapplying two separate beams of ultrasound waves — one of low frequency and one of highfrequency — can uniformly boost permeability across a region of skin more rapidly than usinga single beam of ultrasound waves.Senior authors of the paper are Daniel Blankschtein, the Herman P. Meissner ’29 Professorof Chemical Engineering at MIT, and Robert Langer, the David H. Koch Institute Professor atMIT. Other authors include Baris Polat, one of the lead authors and a former doctoral studentin the Blankschtein and Langer groups, and Douglas Hart, a professor of mechanical Anne Trafton, MIT News Office September 14, 2012  In the new study, the MIT team found that combining high and low frequencies offers betterresults. The high-frequency ultrasound waves generate additional bubbles, which are poppedby the low-frequency waves. The high-frequency ultrasound waves also limit the lateralmovement of the bubbles, keeping them contained in the desired treatment area and creatingmore uniform abrasion, Schoellhammer says.“It’s a very innovative way to improve the technology, increasing the amount of drug that canbe delivered through the skin and expanding the types of drugs that could be delivered thisway,” says Samir Mitragotri, a professor of chemical engineering at the University ofCalifornia at Santa Barbara, who was not part of the research team.The researchers tested their new approach using pig skin and found that it boostedpermeability much more than a single-frequency system. First, they delivered the ultrasoundwaves, then applied either glucose or inulin (a carbohydrate) to the treated skin. Glucose wasabsorbed 10 times better, and inulin four times better. “We think we can increase theenhancement of delivery even more by tweaking a few other things,” Schoellhammer says. Noninvasive drug delivery Such a system could be used to deliver any type of drug that is currently given by capsule,potentially increasing the dosage that can be administered. It could also be used to deliverdrugs for skin conditions such as acne or psoriasis, or to enhance the activity of transdermal  10/2/2014Getting (drugs) under your skin | MIT Newshttp://newsoffice.mit.edu/2012/ultrasound-waves-and-drug-delivery-09143/3 About This Website This Website is maintained by the MIT News Office.MIT News Office ã Building 11-400Massachusetts Institute of Technology ã Cambridge, MA 02139-4307 Topics:patches already in use, such as nicotine patches.Ultrasound transdermal drug delivery could also offer a noninvasive way for diabetics tocontrol their blood sugar levels, through short- or long-term delivery of insulin, theresearchers say. Following ultrasound treatment, improved permeability can last up to 24hours, allowing for delivery of insulin or other drugs over an extended period of time.Such devices also hold potential for administering vaccines, according to the researchers. Ithas already been shown that injections into the skin can induce the type of immune responsenecessary for immunization, so vaccination by skin patch could be a needle-free, pain-freeway to deliver vaccines. This would be especially beneficial in developing countries, since thetraining required to administer such patches would be less intensive than that needed to giveinjections. The Blankschtein and Langer groups are now pursuing this line of research.They are also working on a prototype for a handheld ultrasound device, and on ways toboost skin permeability even more. Safety tests in animals would be needed before humantests can begin. The U.S. Food and Drug Administration has previously approved single-frequency ultrasound transdermal systems based on Langer and Blankschtein’s work, so theresearchers are hopeful that the improved system will also pass the safety tests.The research was funded by the National Institutes of Health.Chemistry and chemical engineeringDiabetesDrug deliveryKoch InstituteResearchVaccinationVaccinesDual-frequency ultrasoundInsulinTransdermalMechanical engineering
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