Ultrasound Mediated Transdermal Insulin Delivery in Pigs Using a Lightweight Transducer
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In previous studies, ultrasound mediated transdermal drug delivery has shown a promising potential as a method for noninvasive drug administration. For prospective future human application, this study was designed to determine the feasibility of lightweight cymbal transducer array as a practical device for noninvasive transdermal insulin delivery in large pigs.
Materials and Methods
Six Yorkshire pigs (100–140 lbs) were divided into two groups. As the control (n = 3), the first group did not receive any ultrasound exposure with the insulin. The second group (n = 3) was treated with ultrasound and insulin at 20 kHz with an Isptp = 100 mW/cm2 at a 20% duty cycle for 60 min. With the pigs in lateral recumbency after anesthesia, the ultrasound transducer with insulin was placed on the axillary area of the pig. At the beginning and every 15 min up to 90 min, the blood glucose level was determined using a glucose monitoring system. To compare the results of individual animals, the change of blood glucose level was normalized to each animal’s initial glucose value at the start of the experiment.
Although each animal had a different initial glucose level, the mean and standard error for the six animals was 146 ± 13 mg/dl. For the control group, the blood glucose level increased to 31 ± 21 mg/dl compared to the initial baseline over the 90 min experiment. However for the ultrasound with insulin treated group, the glucose level decreased to −72 ± 5 mg/dl at 60 min (p < 0.05) and continued to decrease to −91 ± 23 mg/dl in 90 min (p < 0.05).
The results indicate the feasibility of ultrasound mediated transdermal insulin delivery using the cymbal transducer array in animal with a similar size and weight to a human. Based on these result, the cymbal array has potential as a practical ultrasound system for noninvasive transdermal insulin delivery for diabetes management.
Key wordsdiabetes drug delivery insulin transducer ultrasound
This work was supported by the Department of Defense Technologies for Metabolic Monitoring Award Number W81XWH-05-1-0617.
- 15.N. B. Smith. Perspectives on transdermal ultrasound mediated drug delivery. International Journal of Nanomedicine 2(2). (2007). (in press).Google Scholar
- 16.Congressionally established diabetes research working group. Conquering diabetes: a strategic plan for the 21th century. NIH Publication No. 99-4398. 1999.Google Scholar
- 17.The Whitaker Foundation. Biomedical engineering and the fight against diabetes, 2003 Annual Report. The Whitaker Foundation, Arlington, VA, 2004.Google Scholar
- 21.A. Boucaud, L. Tessier, L. Machet, L. Vaillant, and F. Patat. Transdermal delivery of insulin using low frequency ultrasound. In Proceedings of the IEEE 2000 Ultrasonics Symposium, San Juan Porto Rico, 2000, pp. 1453–1456.Google Scholar
- 25.D. Stansfield. Underwater electroacoustic transducers. Bath University Press, Bath, UK, 1990.Google Scholar
- 26.O. B. Wilson. An introduction to the theory and design of sonar transducers. Peninsula, Los Altos, CA, 1988.Google Scholar
- 27.K. K. Shung, M. B. Smith, and B. Tsui. Principles of medical imaging. Academic, San Diego, 1992.Google Scholar
- 28.R. E. Newnham, Q. C. Xu, and S. Yoshikawa. Transformed stress direction acoustic transducer. US Patent 4,999,819, March 12, 1991.Google Scholar
- 29.R. E. Newnham, Q. C. Xu, and S. Yoshikawa. Metal-electroactive ceramic composite actuators. US Patent 5,276,657, January 4, 1994.Google Scholar
- 37.IEEE. IEEE guide for medical ultrasound field parameter measurements. Institute of Electrical and Electronics Engineers, Inc., New York, 1990.Google Scholar
- 38.AIUM. Acoustic output labeling standard for diagnostic ultrasound equipment. American Institute of Ultrasound in Medicine, Laurel, MD, 1998.Google Scholar
- 39.W. G. Pond and K. A. Houpt. The biology of the pig. Cornell University Press, Ithaca, NY, 1978.Google Scholar
- 40.D. Danfaer. A quantitative biology of the pig. CABI, New York, NY, 1998.Google Scholar
- 42.J. E. Harkness and D. J. Wagner. The biology and medicine of rabbits and rodents. Williams and Willkins, Baltimore MD, 1995.Google Scholar
- 43.M. Pavlovic, K. Wroblewski, Y. Manevich, S. Kim, and J. E. Biaglow. The importance of choice of anaesthetics in studying radiation effects in the 9L rat glioma. Br. J. Cancer., Suppl. 27:S222–S225 (1996).Google Scholar
- 44.E. Hillyer and K. E. Quesenberry. Ferrets, rabbits, and rodents: clinical medicine and surgery. Saunders, Philadelphia PA, 1997.Google Scholar
- 47.H. Rifkin and D. Porte. Ellenberg and rifkin’s diabetes. Elsevier, New York, NY, 1990.Google Scholar