The Effects of Extracorporeal Shockwave Mediated Transdermal Drug Delivery in Rat Caudal Nerves

• Main Authors: Wan-Ting Huang, 黃琬葶
• Other Authors: Jer-Junn Luh
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/76885993173308713706

碩士 === 國立臺灣大學 === 物理治療學研究所 === 100 === Background and Purpose: Traditionally, low-frequency ultrasound is used for sonophoresis and has been found to be an effective method in enhancing transdermal drug transport. The generally accepted mechanism responsible for skin permeability enhancement by sonophoresis is the cavitation effect. Extracorporeal shockwave can provide more transient cavitation than most other forms of medical ultrasound, with less thermal effect. Thus, it might have better clinical effects than ultrasound in sonophoresis. However, extracorporeal shockwave might induce nerve damage and cause uncomfortable sense on human skin. Therefore to determine the reasonable dosage of shockwave to reduce the uncomfortableness and induce better compliance of patients is crucial for safety consideration. There is no study founded to explore the sonophoretic effect of shockwave on transdermal delivery of anesthetic drug. Therefore, the purposes of this study were (1) to use the determined suitable parameters of shockwave to identify the sonophoretic effect of extracorporeal shockwave by using the pre- or concurrent shockwave-aided EMLA(eutectic mixture of local anesthetics) application, and simultaneously compared with the sonophoresis-aided EMLA application and topical EMLA application via an animal study. (2) to determine the dose-response of the sonophoretic effect of extracorporeal shockwave with lower intensities or pulses. Methods: Twenty-four Wistar rats with a mean age of 20.9 weeks were used as the experimental subject in this study. In the shockwave sonophoresis study, the rats were assigned to following groups randomly: topical, sonophoresis-aided (1MHz ultrasound), pre- and concurrent shockwave-aided EMLA application on the rat tails for 60 minutes. The degree of anesthesia was assessed using the amplitude and latency of sensory nerve action potential which were evaluated by nerve conduction study (VikingQuest, Nicolet, VIASYS Healthcare, USA) before and every 5 minutes after treatment for 60 min. One week later, in the dose-response study, rats were divided into four groups to received shockwave mediated EMLA delivery with different pulse number and intensity to determine the possible minimal dosage in this application. Results: The pre-treated and concurrent shockwave could provide better effectiveness on transdermal delivery of EMLA cream on the nerve of tail than pre-treated 1 MHz ultrasound (p<0.05). Besides, the concurrent shockwave mediated drug delivery was superior to pre-treated shockwave (p<0.05). After the concurrent shockwave application, the effects of EMLA were evident within 5 minutes, which is much quicker than pre-treatment shockwave application (p<0.05). The concurrent extracorporeal shockwave with lower intensity of 0.055 mJ/mm2 or lower 500 pulse could also show better effectiveness on transdermal delivery of EMLA cream on caudal nerve in healthy male adult rats than topical EMLA application (p<0.05). Conclusions: The safety parameters of 4Hz, 1000 pulses with 0.089mJ/mm2 intensity of extracorporeal shockwave could show better effectiveness on transdermal delivery of EMLA cream than sonophoresis-aided EMLA application, and resulted in better degree of anesthesia and shortening the onset time of anesthetic effect to 5 minutes on caudal nerve in healthy male adult rats. It would be that the concurrent shockwave-aided EMLA application was superior to the pre shockwave-aided EMLA application. Lower intensities (0.055mJ/mm2) or pulses (500 pulse) of extracorporeal shockwave might be the minimal threshold for shockwave sonophoresis and could show better effectiveness on transdermal delivery of EMLA cream than the topical EMLA application.