Drug Delivery by Phonophoresis

Phonophoresis is defined as the migration of drug molecules, contained in a contact agent, through the skin under the influence of ultrasound. Several drugs have been introduced into the body by this technique. The design of a phonophoretic drug delivery system is in developmental stages in various research laboratories. Parameters affecting the delivery of drugs by this technique and devices available for drug delivery purposes are discussed in this review.     

物理疗法在国外的临床应用

物理疗法在各种临床疾病的治疗和很多疾病的康复中发挥了巨大的作用,尽管目前物理疗法处于发展比较缓慢时期,但国外依然有一些新的物理疗法问世,另外,有关一些物理因子的生物效应的研究和一些物理疗法应用技术等方面都有一些进展,作者在回顾近几年来部分国外理疗、康复医学文献的基础上,分别对电疗法(直流电、低频电刺激、中频电疗法、高频电疗法)、光疗法、磁疗法、超声波疗法、冷疗法的国外临床应用进展做以介绍。     

低频超声影响恩纳局部镇痛起效时间的随机对照研究

背景许多动物实验表明,低频超声波可促进药物经皮吸收的速率.本研究已采用低频超声波介导局麻药来测定在人体透皮的速度与深度.目的探讨低频超声波对恩纳局部镇痛起效时间的影响,为临床研究低频超声给药和扩大恩纳的临床应用提供依据.设计采用双盲同体配对随机对照研究.地点和对象研究在解放军第四军医大学秦都医院完成,所有研究对象为解放军第四军医大学学员.干预对24例健康青年志愿者的双上臂采用随机数字分为试验组和对照组,每个试验者两上臂同时涂抹1 g恩纳,10 min后试验组上臂进行低频超声(20 kHz)介导,强度为0.5 W/cm2,介导时间10min.主要观察指标用美国产TranscucerIndication Model 1601C尼龙棒机械压力测痛仪每5 min测量两组镇痛起始时间,共观察2 h.试验结束后观察皮肤组织学变化.结果低频超声干预组平均镇痛起始时间为(34.58±3.87)min,对照组为(43.75±4.72)min.两组镇痛起效时间差异有显著性意义(t=7.62,P＜0.01).低频超声可使角质层间质增宽和疏松.结论低频超声可以促进恩纳透过皮肤,缩短恩纳局部镇痛起效时间.     

Sonophoresis: recent advancements and future trends

Objectives Use of ultrasound in therapeutics and drug delivery has gained importance in recent years, evident by the increase in patents filed and new commercial devices launched. The present review discusses new advancements in sonophoretic drug delivery in the last two decades, and highlights important challenges still to be met to make this technology of more use in the alleviation of diseases. Key findings Phonophoretic research often suffers from poor calibration in terms of the amount of ultrasound energy emitted, and therefore current research must focus on safety of exposure to ultrasound and miniaturization of devices in order to make this technology a commercial reality. More research is needed to identify the role of various parameters influencing sonophoresis so that the process can be optimized. Establishment of long‐term safety issues, broadening the range of drugs that can be delivered through this system, and reduction in the cost of delivery are issues still to be addressed. Summary Sonophoresis (phonophoresis) has been shown to increase skin permeability to various low and high molecular weight drugs, including insulin and heparin. However, its therapeutic value is still being evaluated. Some obstacles in transdermal sonophoresis can be overcome by combination with other physical and chemical enhancement techniques. This review describes recent advancements in equipment and devices for phonophoresis, new formulations tried in sonophoresis, synergistic effects with techniques such as chemical enhancers, iontophoresis and electroporation, as well as the growing use of ultrasound in areas such as cancer therapy, cardiovascular disorders, temporary modification of the blood‐brain barrier for delivery of imaging and therapeutic agents, hormone replacement therapy, sports medicine, gene therapy and nanotechnology. This review also lists patents pertaining to the formulations and techniques used in sonophoretic drug delivery.     

生物大分子药物的经皮给药

对多肽、蛋白质等生物大分子的经皮给药研究的最新进展进行综述     

Effect of dextrose phonophoresis versus pulsed electromagnetic field on temporomandibular dysfunction: A randomized,controlled study

ObjectiveThis study investigated and compared the efficacy of dextrose phonophoresis and Pulsed Electromagnetic Field (PEMF) on pain, range of motion (ROM) and function in patients with Temporomandibular Dysfunction (TMD).Methods45 patients with TMD aging from 25 to 45 years, with mean age 29 ± 2.5 years were included in this study, they were assigned randomly into 3 equal groups each contain fifteen TMJ dysfunction patients. Group (A) in which each patient received 50% dextrose phonophoresis for 5 min and therapeutic ultrasound for 5 min, Group (B) in which each patient received Pulsed Electromagnetic Field (PEMF) with frequency of 50 HZ for 50 min, and traditional physiotherapy ultrasound for 5 min, while in the control group (C) the patients received traditional physiotherapy ultrasound for 5 min only, the frequency of treatment session in the three groups was 3 days per week for 4 weeks. The assessment tools were visual analog scale (VAS) for pain evaluation, plastic ruler for TMJ ROM measurements while Fonseca's questionnaire was used for evaluation of TM function at baseline and 4 weeks later.ResultsPaired t-test for comparison between pre and post treatment measurements in each group showed significant decrease pain as well as improvement of ROM and Fonseca's questionnaire in group A and B than placebo group.ConclusionsThe results found that both dextrose phonophoresis and PEMF have beneficial effects considering pain, ROM and function in patients with (TMD).     

Drug delivery into the eye with the use of ultrasound.

OBJECTIVE: To evaluate ultrasound enhancement of drug delivery through the cornea and the histologic appearance of the cornea up to 24 hours after treatment. METHODS: Corneas were exposed to ultrasound at a frequency of 880 kHz and intensities of 0.19 to 0.56 W/cm2 (continuous mode) with an exposure duration of 5 minutes. The aqueous humor concentration of a topically applied hydrophilic dye, sodium fluorescein, was determined quantitatively in ultrasound- and sham-treated rabbit eyes in vivo. Gross and light microscopic examinations were used to observe structural changes in the cornea 0 to 24 hours after ultrasound exposure. Cavitation activity was measured with a passive cavitation detector. RESULTS: Most cells with an appearance different from that of the normal cells were present in the surface layer of the corneal epithelium. No structural changes were observed in the stroma. The increase in dye concentration in the aqueous humor (relative to sham treatment), after the simultaneous application of ultrasound and the dye solution, was 2.4 times at 0.19 W/cm2, 3.8 times at 0.34 W/cm2, and 10.6 times at 0.56 W/cm2 (P <.05). Dye delivery was found to increase with increasing ultrasound intensity, which corresponded to an increase in cavitation activity. Corneal pits, observed in the ultrasound-treated epithelium, completely disappeared within 90 minutes. CONCLUSIONS: Application of 880-kHz ultrasound provided up to 10-fold enhancement in the delivery of a hydrophilic compound through the cornea while producing minor changes in the corneal epithelium.     

The effect of topical caffeine on the morphology of swine hypodermis as measured by ultrasound

Background  Cellulite or lipodystrophy involves the modification of the subcutaneous adipose tissue. A wide variety of topical products is available to combat cellulite, but these have difficulties in being absorbed through the skin. One option is the therapeutic use of the ultrasound to enhance the transdermic transport of these drugs.
Aim  The objective of this study was the analysis of the effect of caffeine on the morphology of the swine hypodermis, both when applied topically and in combination with ultrasound treatment.
Methods  The following treatments were applied to the dorsal areas of five pigs (Landrace × Large White, 35 days old, weighing 15 kg each): gel, gel + ultrasound, gel + caffeine (5%, w/w), and gel + caffeine + ultrasound, daily for 15 days. A fifth area received no topical application and was used as a control. Continuous ultrasound of 3 MHz with an intensity of 0.2 W/cm² was applied at a rate of 1 min/cm². After histological processing (hematoxylin and eosin), morphometric analyses were conducted to determine the thickness and numerical profile of the hypodermis. A one-way analysis variance using a Kolmogorov–Smirnov test was conducted, with a Tukey test used to identify significant differences. A confidence level of P  ≤ 0.05 was adopted.
Results  Caffeine treatment was effective only when associated with ultrasound therapy; the combination resulted in a significant reduction in the thickness of the subcutaneous adipose tissue, as well as damage to the adipocytes, consequently decreasing the number of cells.
Conclusion  Ultrasound treatment was effective in increasing the cutaneous permeation of caffeine, as evidenced by the reduction in thickness of the hypodermis and number of adipocytes.     

低强度超声丹参透入疗法对骨折愈合影响的实验研究

目的：观察低强度超声丹参透入疗法对骨折愈合的影响。方法：45只新西兰大耳白兔,人为造成右桡骨中段3 mm骨质缺损作为骨折模型,随机分为3组：超声波治疗组（超声组）,超声波联合外用丹参治疗组（实验组）和对照组（不做任何治疗）,分别在术后2、4、6周行 X线检查,进行评分,同时观察比较X线片骨痂灰度值。对部分骨折组织行组织病理检查,从组织学角度观察分析骨折愈合情况。结果：X线检查结果显示实验组骨折愈合较超声组和对照组均提前。术后2、4、6周时 X线评分值,X线骨痂灰度值,实验组均高于超声组和对照组（P〈0.01）。组织病理结果显示,实验组在机化血肿,纤维、软骨、骨性骨痂生长等方面都优于对照组和超声组。结论：超声波丹参透入疗法对骨折愈合有较好的促进作用。     

小b 值表观扩散系数图监测子宫肌瘤高能聚焦超声后疗效的价值

目的：探讨小 b值表观扩散系数图(ADC maps)监测子宫肌瘤高能聚焦超声(HIFU)术后消融灶的价值。方法收集25例共34个子宫肌瘤患者进行HIFU治疗,所有患者术前、术后24 h内均行常规MRI、CE-T1 WI及b值分别取150、600、1000 s/mm2的单指数扩散加权成像(DWI)检查。采用单因素方差分析分析各b值术前、术后消融灶和残留未消融灶的平均ADC值变化。对各b值的ADC伪彩图消融灶与增强MRI的吻合度进行分级评定。结果 b值为150 s/mm2时,术后消融灶平均ADC值[(1.48±0.27)×10-3 mm2/s]低于术前[(2.06±0.21)×10-3 mm2/s]及残留未消融灶平均ADC值[(1.98±0.23)×10-3 mm2/s](P<0.05);b值为600、1000 s/mm2消融灶术前、术后ADC值以及残留未消融灶平均ADC值差异无统计学意义(P>0.05)。b值为150 s/mm2的ADC伪彩图消融灶与增强MRI的无灌注区域容积(non-perfused volume,NPV)有较高视觉吻合,优于 b 值为600、1000 s/mm2 ADC 图消融灶(P<0.05)。结论小b值(150 s/mm2)ADC图可间接反映子宫肌瘤HIFU治疗后的血供改变和消融范围,借此评估治疗效果。