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Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light-weight cymbal array.
Diabetes Technol Ther. 2004 Dec; 6(6):808-15.DT

Abstract

OBJECTIVE

Recent studies have shown that ultrasound-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to demonstrate ultrasonic transdermal delivery of insulin in vivo using rabbits with a novel, low-profile two-by-two ultrasound array based on the cymbal transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 x 37 x 7 mm3 in size and weighed less than 22 g. Using the same array on hyperglycemic rats, our previous experiments demonstrated that blood glucose would decrease 233.3 +/- 22.2 mg/dL in 90 min from 5 min of pulsed ultrasound exposure. With a similar intensity (Isptp = 100 mW/cm2, 20% duty cycle), our goal was to determine if the same effect could be achieved with rabbits.

METHODS

Experiments were performed in 16 New Zealand White rabbits (weighing 2.7-3.4 kg) divided into three groups: two controls and one ultrasound with insulin exposure. The rabbits were first anesthetized, and their thigh area was shaved for the exposure area. While the animal was lying in the lateral recumbent position, a 1-mm-thick, water-tight standoff (reservoir) that held insulin or saline was fastened between the thigh and the ultrasound array. The first control group (control 1: insulin-no ultrasound) had insulin placed in the reservoir with no ultrasound exposure, while the second control group (control 2: saline-ultrasound) had saline in the reservoir with ultrasound operating at Isptp = 100 mW/cm2 for 60 min. The third rabbit group (ultrasound-insulin) was subjected to insulin with ultrasound exposure for 60 min (Isptp = 100 mW/cm2). At the beginning of the experiment and every 15 min for 90 min, 0.3 mL of blood was collected from the ear vein to determine the blood glucose level (in mg/dL) using a glucose monitoring system. For comparison between individual rabbits, the change in the blood glucose level was normalized to a baseline value. The insulin reservoir was removed with the array after the ultrasound was turned off at 60 min of exposure.

RESULTS

For both controls, insulin-no ultrasound and saline-ultrasound, the blood glucose level varied from the initial baseline by approximately +75 mg/dL. However, for the ultrasound-insulin group, the glucose level was found to decrease to -132.6 +/- 35.7 mg/dL from the initial baseline in 60 min. Even after the array and insulin reservoir were removed, the blood glucose level of ultrasound-insulin group continued to decrease to -208.1 +/- 29 mg/dL from the initial baseline.

CONCLUSIONS

These results indicate the feasibility of using a low-cost, lightweight cymbal array for enhanced transdermal insulin delivery using ultrasound.

Authors+Show Affiliations

Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15684633

Citation

Lee, Seungjun, et al. "Noninvasive Ultrasonic Transdermal Insulin Delivery in Rabbits Using the Light-weight Cymbal Array." Diabetes Technology & Therapeutics, vol. 6, no. 6, 2004, pp. 808-15.
Lee S, Snyder B, Newnham RE, et al. Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light-weight cymbal array. Diabetes Technol Ther. 2004;6(6):808-15.
Lee, S., Snyder, B., Newnham, R. E., & Smith, N. B. (2004). Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light-weight cymbal array. Diabetes Technology & Therapeutics, 6(6), 808-15.
Lee S, et al. Noninvasive Ultrasonic Transdermal Insulin Delivery in Rabbits Using the Light-weight Cymbal Array. Diabetes Technol Ther. 2004;6(6):808-15. PubMed PMID: 15684633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light-weight cymbal array. AU - Lee,Seungjun, AU - Snyder,Benjamin, AU - Newnham,Robert E, AU - Smith,Nadine Barrie, PY - 2005/2/3/pubmed PY - 2005/5/27/medline PY - 2005/2/3/entrez SP - 808 EP - 15 JF - Diabetes technology & therapeutics JO - Diabetes Technol Ther VL - 6 IS - 6 N2 - OBJECTIVE: Recent studies have shown that ultrasound-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to demonstrate ultrasonic transdermal delivery of insulin in vivo using rabbits with a novel, low-profile two-by-two ultrasound array based on the cymbal transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 x 37 x 7 mm3 in size and weighed less than 22 g. Using the same array on hyperglycemic rats, our previous experiments demonstrated that blood glucose would decrease 233.3 +/- 22.2 mg/dL in 90 min from 5 min of pulsed ultrasound exposure. With a similar intensity (Isptp = 100 mW/cm2, 20% duty cycle), our goal was to determine if the same effect could be achieved with rabbits. METHODS: Experiments were performed in 16 New Zealand White rabbits (weighing 2.7-3.4 kg) divided into three groups: two controls and one ultrasound with insulin exposure. The rabbits were first anesthetized, and their thigh area was shaved for the exposure area. While the animal was lying in the lateral recumbent position, a 1-mm-thick, water-tight standoff (reservoir) that held insulin or saline was fastened between the thigh and the ultrasound array. The first control group (control 1: insulin-no ultrasound) had insulin placed in the reservoir with no ultrasound exposure, while the second control group (control 2: saline-ultrasound) had saline in the reservoir with ultrasound operating at Isptp = 100 mW/cm2 for 60 min. The third rabbit group (ultrasound-insulin) was subjected to insulin with ultrasound exposure for 60 min (Isptp = 100 mW/cm2). At the beginning of the experiment and every 15 min for 90 min, 0.3 mL of blood was collected from the ear vein to determine the blood glucose level (in mg/dL) using a glucose monitoring system. For comparison between individual rabbits, the change in the blood glucose level was normalized to a baseline value. The insulin reservoir was removed with the array after the ultrasound was turned off at 60 min of exposure. RESULTS: For both controls, insulin-no ultrasound and saline-ultrasound, the blood glucose level varied from the initial baseline by approximately +75 mg/dL. However, for the ultrasound-insulin group, the glucose level was found to decrease to -132.6 +/- 35.7 mg/dL from the initial baseline in 60 min. Even after the array and insulin reservoir were removed, the blood glucose level of ultrasound-insulin group continued to decrease to -208.1 +/- 29 mg/dL from the initial baseline. CONCLUSIONS: These results indicate the feasibility of using a low-cost, lightweight cymbal array for enhanced transdermal insulin delivery using ultrasound. SN - 1520-9156 UR - https://www.unboundmedicine.com/medline/citation/15684633/Noninvasive_ultrasonic_transdermal_insulin_delivery_in_rabbits_using_the_light_weight_cymbal_array_ L2 - https://www.liebertpub.com/doi/10.1089/dia.2004.6.808?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -