Background: Noninvasive transdermal insulin delivery using ultrasound technology has gained attention for improving the glycemic control of insulin-dependent patients. Methods: Indirect functional comparison and evaluation of insulin dosage, between noninvasive ultrasound-mediated transdermal delivery and needle injection methods, was achieved utilizing in vivo blood glucose measurements of temporary hyperglycemic rabbits. Nine rabbits were divided into three groups: (i) untreated control, (ii) subcutaneous injection and (iii) ultrasound-mediated transdermal delivery. Animals were anesthetized using a combination of ketamine hydrochloride and sodium xylazine to produce temporary hyperglycemic rabbits during the experiments. The rabbits in the control group did not receive insulin, while the animals in the ultrasound group received insulin transdermally for 10 min utilizing a customized single-element piston-shaped ultrasound transducer operated by multi-frequency electrical signals from 100 to 200 kHz. Rabbits in the direct subcutaneous injection group were anesthetized and injected with 0.25 units/kg of insulin. Results: With an initial blood glucose baseline level of 228.7 ± 13.1 (mg/dL) for all rabbits, the in vivo results of control group showed an increase above the baseline by 129.7 ± 27.3 (mg/dL) at the end of the in vivo experimental period (80 min). However, the ultrasound-mediated delivery and subcutaneous injection groups showed noticeable statistically significant percentage reductions in blood glucose levels by 43.9 ± 5.4 and 42.7 ± 6.6, respectively, compared to the control group by the end of the in vivo experiments. Conclusions: In vivo glucose response results confirmed that piston-shaped ultrasound transducers achieved indirectly similar insulin dosage delivery by ultrasound energy for tested animals with no statistically significant differences once compared to the results of the subcutaneous needle injection group.
Al-Bataineh et al. (Wed,) studied this question.