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Using an Animal Study to Evaluate the Role of Thermal Effect in Therapeutic Ultrasound Mediated Transdermal Drug Delivery

以動物實驗探討熱效應於超音波導入中之角色

摘要


背景與目的:超音波導入(sonophoresis)是一種非侵入性、以超音波為基礎的經皮膚藥物輸送技術。然而至今,使用治療用超音波進行超音導入時之熱效應(thermal effect)之重要性不明確。本研究的目的在於以動物實驗評估1MHz超音波進行超音波導入時之熱效應的影響。方法:大自鼠分為超音波導入組、熱效應組、以及控制組,超音波導入組在尾部接受超音波照射(1MHz, 2W/平方公分,100% duty cycle, 5分鐘)後塗上局部麻醉藥物安麻樂(eutectic mixture of local anesthetics, EMLA);而熱效應組則在50℃熱水浴10分鐘後塗上EMLA;而控制組則單純只塗上EMLA。尾部神經之感覺神經傳導檢查則在治療前、治療後、以及治療後每5分鐘進行量測至治療後60分鐘。結果:在控制組與熱效應組治療前後之感覺神經傳導速率(sensory nerve conduction velocity, SNCV)下降率或感覺神經動作電位(sensory nerve action potential, SNAP)下降率皆沒有明顯差別。而在超音波治療組SNCV下降至原始速度之20%時所需的時間明顯較控制組及熱效應組為少。相較於控制組與熱效應組,超音波治療組約可將EMLA發生作用的時間由60分鐘縮短至20分鐘以內看。結論:由本研究結論可知,在使用IMHz治療用超音波進行超音導入,超音熱效應的重要性應小於超音波之機械效應。

並列摘要


Background and Purpose: Sonophoresis is a noninvasive ultrasound-based method for the transdermal delivery of drugs. However, the importance of the thermal effects in sonophoresis via therapeutic ultrasound remained unclear. In this study, an animal study was used to evaluate the contribution of thermal effects in 1MHz ultrasound mediated transdermal drug delivery. Method: Rats in the ultrasound-treatment, heat-treatment, and control groups received ultrasound treatments (1MHz, 2W/cm^2, 100% duty cycle, 5 min), heat treatment (tail in 50℃ water-bath for 10 min), and no treatment, respectively, before applying eutectic mixture of local anesthetics (EMLA) cream. Sensory conduction in the tail nerve was investigated before and every 5 min after treatment for 60 min. Results: There was no significant difference between the control and heat-treatment groups in the latency to the reduction in sensory nerve conduction velocity (SNCV) or in the sensory nerve action potential (SNAP) amplitude. The latency for the SNCV to decrease by 20% was significantly lower in the ultrasound-treatment group than in the control and thermal-treatment groups. Compared with control group and thermal treatment group, using ultrasound could reduce the latency for an EMLA reaction from 60 min to less than 20 min. Conclusion: In this study, the thermal effect seemed less important than the mechanical effects in sonophoresis via therapeutic ultrasound.

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