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Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection.

Park EJ, Dodds J, Smith NB - Int J Nanomedicine (2008)

Bottom Line: Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array.The change in blood glucose from baseline was compared between groups.Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190 +/- 96 mg/dl (mean +/- SD) at 90 minutes.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802, USA.

ABSTRACT
Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array. In this study the physiologic response to ultrasound mediated transdermal insulin delivery is compared to that of subcutaneously administered insulin. Anesthetized rats (350-550 g) were divided into four groups of four animals; one group representing ultrasound mediated insulin delivery and three representing subcutaneously administered insulin (0.15, 0.20, and 0.25 U/kg). The cymbal array was operated for 60 minutes at 20 kHz with 100 mW/cm2 spatial-peak temporal-peak intensity and a 20% duty cycle. The blood glucose level was determined at the beginning of the experiment and, following insulin administration, every 15 minutes for 90 minutes for both the ultrasound and injection groups. The change in blood glucose from baseline was compared between groups. When administered by subcutaneous injection at insulin doses of 0.15 and 0.20 U/kg, there was little change in the blood glucose levels over the 90 minute experiment. Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190 +/- 96 mg/dl (mean +/- SD) at 90 minutes. The change in blood glucose following ultrasound mediated insulin delivery was -262 +/- 40 mg/dl at 90 minutes. As expected, the magnitude of change in blood glucose between the three injection groups was dependant on the dose of insulin administered. The change in blood glucose in the ultrasound group was greater than that observed in the injection groups suggesting that a higher effective dose of insulin was delivered.

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(A) For the cymbal array made up of four cymbal transducers, the cymbal elements were connected in parallel, encased in URALITE® polymer and arranged in a two-by-two elemental pattern. The dimensions of the array were 37 × 37 × 7 mm3 and it weighed less than 20 g. (B) Photograph of a transdermal insulin delivery experiment with a rat placed in a dorsal decubitus position with the array attached. A 1 mm thick water tight standoff was arranged between the abdominal area and the array. The reservoir within the standoff was filled with insulin through a small hole in the back of the array.
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f1-ijn-3-335: (A) For the cymbal array made up of four cymbal transducers, the cymbal elements were connected in parallel, encased in URALITE® polymer and arranged in a two-by-two elemental pattern. The dimensions of the array were 37 × 37 × 7 mm3 and it weighed less than 20 g. (B) Photograph of a transdermal insulin delivery experiment with a rat placed in a dorsal decubitus position with the array attached. A 1 mm thick water tight standoff was arranged between the abdominal area and the array. The reservoir within the standoff was filled with insulin through a small hole in the back of the array.

Mentions: Details regarding the design and construction of the cymbal transducer and the multi-element array have been described elsewhere (Newnham et al 1991, 1994; Maione et al 2002). Briefly, the cymbal transducer is a novel flextensional transducer capable of producing very low frequencies (Figure 1a). A cymbal transducer has a compact, lightweight structure with an adjustable resonance frequency. In the cymbal transducer design, the caps on the lead zirconate – titanate (PZT) ceramic contained a shallow cavity beneath the inner surface. The fundamental mode of vibration is the flexing of the end caps caused by the radial motion of the ceramic. Therefore, the overall displacement of the device is a combination of the axial motion of the disk plus the radial motion amplified by the end caps. Amplification factors can be as high as 40 times that of the ceramic by itself (Meyer et al 2001). Specifically, the piezoelectric disc was made from PZT-4 (Piezokinetics, Inc., Bellefonte, PA), had a diameter of 12.7 mm, and was 1 mm thick. Caps were made of 0.25-mm thick titanium while the thin glue layer between the caps and the ceramic disk was made of Eccobond® (Emerson and Cuming, Billerica, MA) epoxy. For the array, four transducers were connected in parallel and encased in URALITE® polymer (FH 3550, H.B. Fuller, St. Paul, MN) to produce a transducer array arrangement.


Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection.

Park EJ, Dodds J, Smith NB - Int J Nanomedicine (2008)

(A) For the cymbal array made up of four cymbal transducers, the cymbal elements were connected in parallel, encased in URALITE® polymer and arranged in a two-by-two elemental pattern. The dimensions of the array were 37 × 37 × 7 mm3 and it weighed less than 20 g. (B) Photograph of a transdermal insulin delivery experiment with a rat placed in a dorsal decubitus position with the array attached. A 1 mm thick water tight standoff was arranged between the abdominal area and the array. The reservoir within the standoff was filled with insulin through a small hole in the back of the array.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2626935&req=5

f1-ijn-3-335: (A) For the cymbal array made up of four cymbal transducers, the cymbal elements were connected in parallel, encased in URALITE® polymer and arranged in a two-by-two elemental pattern. The dimensions of the array were 37 × 37 × 7 mm3 and it weighed less than 20 g. (B) Photograph of a transdermal insulin delivery experiment with a rat placed in a dorsal decubitus position with the array attached. A 1 mm thick water tight standoff was arranged between the abdominal area and the array. The reservoir within the standoff was filled with insulin through a small hole in the back of the array.
Mentions: Details regarding the design and construction of the cymbal transducer and the multi-element array have been described elsewhere (Newnham et al 1991, 1994; Maione et al 2002). Briefly, the cymbal transducer is a novel flextensional transducer capable of producing very low frequencies (Figure 1a). A cymbal transducer has a compact, lightweight structure with an adjustable resonance frequency. In the cymbal transducer design, the caps on the lead zirconate – titanate (PZT) ceramic contained a shallow cavity beneath the inner surface. The fundamental mode of vibration is the flexing of the end caps caused by the radial motion of the ceramic. Therefore, the overall displacement of the device is a combination of the axial motion of the disk plus the radial motion amplified by the end caps. Amplification factors can be as high as 40 times that of the ceramic by itself (Meyer et al 2001). Specifically, the piezoelectric disc was made from PZT-4 (Piezokinetics, Inc., Bellefonte, PA), had a diameter of 12.7 mm, and was 1 mm thick. Caps were made of 0.25-mm thick titanium while the thin glue layer between the caps and the ceramic disk was made of Eccobond® (Emerson and Cuming, Billerica, MA) epoxy. For the array, four transducers were connected in parallel and encased in URALITE® polymer (FH 3550, H.B. Fuller, St. Paul, MN) to produce a transducer array arrangement.

Bottom Line: Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array.The change in blood glucose from baseline was compared between groups.Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190 +/- 96 mg/dl (mean +/- SD) at 90 minutes.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802, USA.

ABSTRACT
Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array. In this study the physiologic response to ultrasound mediated transdermal insulin delivery is compared to that of subcutaneously administered insulin. Anesthetized rats (350-550 g) were divided into four groups of four animals; one group representing ultrasound mediated insulin delivery and three representing subcutaneously administered insulin (0.15, 0.20, and 0.25 U/kg). The cymbal array was operated for 60 minutes at 20 kHz with 100 mW/cm2 spatial-peak temporal-peak intensity and a 20% duty cycle. The blood glucose level was determined at the beginning of the experiment and, following insulin administration, every 15 minutes for 90 minutes for both the ultrasound and injection groups. The change in blood glucose from baseline was compared between groups. When administered by subcutaneous injection at insulin doses of 0.15 and 0.20 U/kg, there was little change in the blood glucose levels over the 90 minute experiment. Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190 +/- 96 mg/dl (mean +/- SD) at 90 minutes. The change in blood glucose following ultrasound mediated insulin delivery was -262 +/- 40 mg/dl at 90 minutes. As expected, the magnitude of change in blood glucose between the three injection groups was dependant on the dose of insulin administered. The change in blood glucose in the ultrasound group was greater than that observed in the injection groups suggesting that a higher effective dose of insulin was delivered.

Show MeSH
Related in: MedlinePlus