ULS types
Range of frequencies
Low-frequency ULS
20–100 KHz
Medium-frequency ULS
0.7 ≥ 3.0 MHz
High-frequency ULS
3.0 ≥ 10.0 MHz
We can observe the principal medical applications of ULS in Table 3.2.
Table 3.2
Important applications of sonophoresis
Significant applications of ULS |
|---|
(i) As a diagnostic tool |
(ii) For physical therapy |
(iii) In sport medicine |
(iv) For drug delivery (transdermal, ocular, and ungual) |
(v) In surgery |
(vi) In gene therapy |
ULS was initially investigated for treating localized skin conditions (Benwell and Bly 1987; Skauen and Zentner 1984) and joint inflammation (McElnay et al. 1985). More recently, there has been considerable interest in developing ULS as a technique to enhance the transdermal delivery of drugs (Mitragotri et al. 1996) and for gene therapy (Kost et al. 2000).
A number of outstanding reviews that have been published in recent years contain comprehensive discussions about many aspects of sonophoresis (Amit and Jaideep 2002; Kushner et al. 2008; Ter Haar 2007; Lavon and Kost 2004; Machet and Boucaud 2002; Merino et al. 2003; Escobar-Chávez et al. 2009a, b, c; Sarah et al. 2011; Modi et al. 2012; Ita 2015). The present chapter shows an updated outline of the therapeutic applications of sonophoresis in the pharmaceutical field and sonophoretic devices offered in the pharmaceutical market. This focus is justified due to the amount of the experimental data and information existing with the use of this technique.
3.2 Ultrasound
Sound is a form of mechanical force that is propagated from one point to another by the interaction between neighboring oscillating particles (Zagzebski 1996). The direction of propagation is parallel to the direction of oscillation, and hence sound is defined as a longitudinal wave (see Fig. 3.1).
Fig. 3.1
Representation of sound wave propagation
An ULS wave is a longitudinal compression wave with frequency above that of the audible range of human hearing (Polat et al. 2011a). Because its propagation depends entirely on the creation of alternating regions of molecular compression and rarefaction, sound cannot exist in a vacuum. Acoustic waves with frequencies between 20 Hz and ~20 KHz fall in the audible range. The term ultrasonic refers to sound waves whose frequency is >20 KHz. The intensity (I, expressed in W/cm2), or concentration of power within a specific area in an ULS beam, is proportional to the square of the amplitude, which is the maximum increase or decrease in the pressure relative to ambient conditions in the absence of the sound wave. The intensity is progressively lost when a sound wave passes through the body, a phenomenon referred to as attenuation. In homogeneous tissue, the attenuation occurs as a result of absorption, in which case the sound energy is transformed into heat and scattered (Escobar-Chávez et al. 2009a, b, c; Weyman 1991). The source of sound waves in a biomedical ULS device is a piezoelectric crystal transducer. The crystal material may be quartz or another polycrystalline material, such as lead zirconate titanate or barium titanate (Escobar-Chávez et al. 2009a, b, c; Weyman 1991). The sound waves are produced in response to an electrical impulse in the piezoelectric crystal, allowing the conversion of electrical into mechanical or vibrational force; this conversion requires a molecular medium (solid, liquid, or gas) to be successful (Fig. 3.2). Following the external perturbation, groups of molecules oscillate in phase and transmit their kinetic energy to nearby molecules (Benwell and Bly 1987). The ULS beam is composed of two fields, the near field, in the region closest to the transducer face, and the far field. The parameters controlling this configuration of the ULS beam are principally the frequency and the dimension of transducer (Escobar-Chávez et al. 2009a, b, c; Weyman 1991). Additional experimental variables (Polat et al. 2011a, b) that are significant in sonophoresis are exposed in Table 3.3.
Fig. 3.2
Disruption of SC by ULS to increase skin permeability
Table 3.3
The most important experimental variables in sonophoretic investigations
Important experimental variables in sonophoresis |
|---|
(i) ULS duty cycle |
(ii) Distance between ULS horn and the skin |
(iii) Treatment time |
(iv) Composition of the ULS coupling medium |
Normally used ULS duty cycles are 10 %, 50 %, or continuous appliance (Mitagroti et al. 1995, 1996, 2000; Boucaud et al. 2001a, b, 2010; Tang et al. 2001; Álvarez-Román et al. 2003; Kushner et al. 2007; Polat et al. 2011; Lee et al. 2010; Smith et al. 2003a) ULS pulsing is common because it decreases thermal effects related with ULS by allowing time for heat to diffuse from the coupling medium for the time of treatment. Many horn-to-skin distances have been used in sonophoresis research, ranging from placing the ULS horn in contact with the skin to as far as 4 cm from the skin surface (Lee et al. 2010; Terahara et al. 2002). Treatment time can also vary greatly, from a not many seconds (Katz et al. 2004; Becker et al. 2005; Brown et al. 2006; Spierings et al. 2008) to a little minutes (Seto et al. 2010) or even to cases where a steady state is attained, which can take many hours to days (Tang et al. 2002a, b). Finally, formulation of the coupling medium is also a very important variable in transdermal sonophoresis. The viscosity, density, surface tension, acoustic impedance, and other bulk and interfacial properties of the coupling medium can all play a significant role in determining the extend of skin permeability enhancement observed as a result of the ULS treatment. Furthermore, the coupling medium can contain the active drug or can include a chemical enhancer (Escobar-Chávez et al. 2010).
3.3 Advantages and Drawbacks of Sonophoresis
Sonophoresis is capable of expanding therapeutic applications, and a variety of compounds can be delivered by topical and transdermal routes and by other nonconventional routes (like ocular and nail drug delivery). The advantages and disadvantages of sonophoresis (Kassan et al. 1996) can be summarized as follows in Table 3.4.
Table 3.4
Advantages and drawbacks of sonophoresis
Advantages | Disadvantages |
|---|---|
Improved drug penetration over passive transport | Can be prolonged to administer |
Allows strict control of transdermal diffusion rates | Minor tingling, irritation, and burning (Maloney et al. 1992) |
The skin remains in one piece | |
A reduced amount of anxiety provoking or painful than injection | |
In many cases, greater patient approval (Escobar-Chávez et al. 2010) | |
Not immunologically sensitizing | |
Less risk of systemic absorption (Escobar-Chávez et al. 2010) | |
It has been used in physiotherapy for rehabilitation (Escobar-Chávez et al. 2010) | |
Helpful to break up blood clots |
3.4 Therapeutic Applications of ULS
3.4.1 Drug Release
3.4.1.1 Topical/Transdermal Drug Release
Transdermal drug delivery has several potential advantages over other parenteral delivery methods. Apart from the convenience and noninvasiveness, the skin also provides a “reservoir” that sustains delivery over a period of days. However, at present, the clinical use of transdermal delivery is limited by the fact that very few drugs can be delivered by transdermal route at a viable rate. This difficulty is because the skin forms an efficient barrier for most molecules, and few noninvasive methods are known to significantly enhance the penetration of this barrier.
In order to increase the range of drugs available for transdermal delivery, the use of ULS has emerged as an interesting and valuable alternative for delivering lipophilic and hydrophilic drugs throughout the SC with the possibility of having a local or systemic effect for treatment of many diverse diseases (Wells 1997; McElnay et al. 1985; Novak 1964; Griffin and Touchstone 1972; Tachibana and Tachibana 1993; Williams 1990; Kim et al. 2007; Hehn and Moll 1996; Meshali et al. 2008; Miyazaki et al. 1992; Tiwari et al. 2004; Yang et al. 2004; Serikov 2007; Cabak et al. 2005; Herwadkar et al. 2012; Rosim et al. 2005; Hippius et al. 1998; Rornanenko and Araviiskii 1991; Ragelis 1981; Liu et al. 2006; Santoianni et al. 2004; Aoi et al. 2007; Meidan et al. 1999; Luis et al. 2007; Lee et al. 2004a, b; Smith et al. 2003a, b; Saliba et al. 2007; Byl et al. 1993; Akinbo et al. 2007; Yang et al. 2006; Machet et al. 1996; McElnay et al. 1993; El-Kamel et al. 2008; Park et al. 2005; Morimoto et al. 2005; Tezel et al. 2004; Boucaud et al. 2001a, b; Sarheed and Abdul Rasool 2011; Menon et al. 1994; Ng and Wong 2008; Andrade et al. 2011; Ebrahimi et al. 2012; Abreu et al. 2013; Cage et al. 2013; Shetty et al. 2013; Feiszthuber et al. 2015; Huang et al. 2015; Ita and Popova 2015; Yu et al. 2015; Park et al. 2016), ungual/transungual (Rao and Nanda 2009; Zderic et al. 2004a, b), and ocular routes (Abadi and Zderic 2011). This is emphasized in Tables 3.5 and 3.6, which summarize the research on sonophoresis uses and many experimental conditions used in the topical/transdermal drug administration (Kushner et al. 2004; Álvarez-Román et al. 2003; Cancel et al. 2004; Paliwal et al. 2006; Walker 1983; Larkin et al. 2008; Khaibullina et al. 2008; Levenets et al. 1989; Matinian et al. 1990).
Table 3.5
Studies on the use of sonophoresis to administer diverse drugs
Topical/transdermal drug release | ||
|---|---|---|
Investigations | Results | Researcher(s) |
Anesthetics | ||
Lidocaine skin penetration | Increased subdermal concentration of lidocaine transmitted into a rabbit when topical application was followed by ULS | Wells (1997) |
Double-blind trial in healthy volunteers for lidocaine cream | No increase in absorption of lidocaine cream by using ULS | McElnay et al. (1985) |
Trial in healthy volunteers for lidocaine oil | Variation in concentrations of lidocaine induces differences in ULS frequencies by the use of ULS | Novak (1964) |
Lidocaine skin permeation | 250 kHz induced the highest penetration of lidocaine | Griffin and Touchstone (1972) |
Anesthetic effect of lidocaine in the legs in hairless mice | ULS in conjunction with a topical aqueous lidocaine solution was rapidly effective in inducing an anesthetic effect in the legs in hairless mice | Tachibana and Tachibana (1993) |
Evaluation of pulsed and continuous modes of therapeutic ULS by investigating the result of lidocaine sonophoresis on sensory obstruction | Pulsed ULS with topical lidocaine gel induced superior anesthetic effect compared with continuous ULS with topical lidocaine gel and lidocaine application alone. The mechanical properties of pulsed ULS appear to be responsible for superior drug diffusion | Ebrahimi et al. (2012) |
Topical sonophoresis of benzocaine and dibucaine | No detectable increase in the rate of anesthetic penetration | Williams (1990) |
Transdermal administration of lidocaine hydrochloride in healthy volunteers applying 0.5-MHz ULS | It was found that deep permeation of lidocaine improved the anesthetic effect by applying 0.5 MHz ULS | Kim et al. (2007) |
Procaine hydrochloride penetration through cell monolayers applying therapeutic ULS | Extent and velocity of the permeation of procaine hydrochloride through cultured Madin-Darby Canine Kidney (MDCK) epithelial cell monolayer can be controlled by sonophoresis | Hehn and Moll (1996) |
Analgesic and anti–inflammatory drugs | ||
Transport of three nonsteroidal anti-inflammatory drugs (NSAIDs) across the cellulose membrane and hairless rabbit skin | Demonstrated the synergistic effect of temperature and ULS operation parameters on drug transport of NSAIDs | Meshali et al. (2008) |
Effect of ULS on transdermal absorption of indomethacin from an ointment in rats | Intensity and duration of application play an important role in transdermal sonophoretic delivery; the intensity of 0.75 W/cm2 for 10 min was the most effective for delivering indomethacin | Miyazaki et al. (1992) |
Study of the influence of ULS on percutaneous absorption of ketorolac tromethamine in vitro across hairless rat skin | A significant increase in permeation of ketorolac through the rat skin was observed with the applied sonication at 3 W/cm2 when compared with permeation at 1 and 2 W/cm2 | Tiwari et al. (2004) |
To determine if a ketorolac tromethamine (KT) gel solution could be administered in vivo via phonophoretic transdermal delivery using pulsed ULS | The transdermal application of KT gel using sonophoresis had significant anti-hyperalgesic and anti-inflammatory effects | Yang et al. (2008) |
Application of ultraphonophoresis of 5 % ibuprofen gel to affected joints of 20 patients | Analgesic efficacy of transcutaneous 5 % gel nurofen in osteoarthrosis | Serikov (2007) |
Examination of therapeutic effects of sonophoresis with ketoprofen in gel form in patients with enthesopathy of the elbow | Positive effects of sonophoresis using a pharmacologically active gel with ketoprofen were shown to be highly significant in both objective and subjective assessments | Cabak et al. (2005) |
To deliver ketoprofen into and across the skin by testing low-frequency sonophoresis at 20 kHz | Low-frequency sonophoresis with optimized ULS parameters can be effectively used to actively enhance transdermal and topical delivery of ketoprofen | Herwadkar et al. (2012) |
Quantitative study of diclofenac sodium (Voltaren Emulgel, Novartis) in phonophoresis in humans | Previously applied therapeutic ULS irradiation enhances the percutaneous penetration of the topical diclofenac gel, although the mechanism remains unclear | Rosim et al. (2005) |
Development of a novel transdermal drug delivery system comprising a polyamidoamine dendrimer together with sonophoresis to improve the penetration of diclofenac (DF) throughout the skin | DF gel without dendrimer and ULS treatment to skin (passive delivery) showed 56.69 μg/cm2 cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment showed 257.3 μg/cm2 cumulative drug permeated through the skin after 24 h. However, when the same gel was applied to sonophoresis-treated skin, great permeation enhancement was observed (935.21 μg/cm2) | Huang et al. (2015) |
Investigation of in vitro penetration and the in vivo transport of flufenamic acid in dependence of ULS | The highest penetration was observed at an intensity of 1.0 W/cm2 after 30 min. These results were not significantly different from concentration measurements after 30 min and 0.5 and 1.5 W/cm2. It seems that the rise of drug concentration is caused by effects of temperature and by variation of membrane delivery in dependence of temperature | Hippius et al. (1998) |
Effects on muscle injury by using sonophoresis of a Lychnophora pinaster gels | Topical application of triterpenes, steroids, and flavonoids of a water and hexane extract of Lychnophora pinaster significantly decreases the inflammatory process generated by muscle injury. Transdermal sonophoresis in rat paws of gel with lupeol and quercetin attenuates the inflammation | Abreu et al. (2013) |
To establish the relative acoustic transmission allowable by various preparations (creams and gels with Arnica montana, menthol, methyl salicylate, capsaicin) at 1 MHz- and 3-MHz ULS frequencies | Topical agents suspended in aqueous gels are generally more effective in transmitting US energy, while many cream-based agents are less effective, particularly at 1-MHz frequency | Cage et al. (2013) |
Drugs for dementia | ||
Enhancement effect of low-frequency sonophoresis on transdermal penetration of rivastigmine in vitro and in vivo | The in vitro permeation study showed that sonophoresis augmented steady-state transdermal flux 0.31 ± 0.03 μg/cm2 h and the extent of rivastigmine permeation 6.00 ± 0.56 μg/cm2 h though excised skin. In the in vivo experiment, the C (max) 0.83 ± 0.16 μg/mL and AUC (0– > 24 h) 12.35 ± 1.99 μg/h.mL of the sonophoresis group was also significantly higher than that of the control group | Yu et al. (2015) |
Antibiotics | ||
Effect of ULS on the delivery of topically applied amphotericin B ointment in guinea pigs | Amphotericin B content in the skin and subcutaneous fatty tissues was much higher when the drug was delivered in the presence of ULS | Rornanenko and Araviiskii (1991) |
Administration of tetracycline in healthy rabbits using electrophoresis and sonophoresis | It was found that the tissue levels of tetracycline administered with the modified methods of electro- and sonophoresis increased with an increase in the current density or ULS intensity | Ragelis (1981) |
Antihypertensives | ||
Effect of ultrasound and chemical penetration enhancers on transcutaneous flux of penbutolol sulfate across split-thickness porcine skin | Low-frequency sonophoresis at a frequency of 20 kHz increased transcutaneous flux of penbutolol sulfate by 3.5-fold (27.37 ± μg/cm2h) compared to passive delivery (7.82 ± 1.72 μg/cm2 h). The results demonstrate that although there were small increases in flux values, ULS, ethanol, and limonene did not significantly improve the transdermal release of penbutolol sulfate | Ita and Popova; (2015) |
The effects of permeation enhancers and sonophoresis on the transdermal permeation of lercanidipine hydrochloride (LRDP) across mouse skin | Sonophoresis considerably increased the cumulative amount of LRDP permeating through the skin in comparison to passive diffusion. A synergistic effect was noted when sonophoresis was applied in the presence of permeation enhancers. The results suggest that the formulation of LRDP with an appropriate penetration enhancer may be useful in the development of a therapeutic system to transport LRDP across the skin for a prolonged period | Shetty et al. (2013) |
Drugs for actinic keratosis | ||
To investigate the effects of fractional radiofrequency (RF) combined with sonophoresis on 5-aminolevulinic acid (ALA) penetration of the skin of male domestic swine | Fluorescence intensity increased after fractional radiofrequency (RF) and increased additionally with the addition of sonophoresis. Fractional RF with sonophoresis efficiently enhanced ALA skin penetration. Pre-fractional RF followed by posttreatment with sonophoresis can be used for ALA-photodynamic therapy to achieve higher ALA uptake | Park et al. (2016) |
Drugs for treatment of hyperhidrosis | ||
Treatment of hyperhidrosis by using phonophoresis or iontophoresis of onabotulinumtoxinA | Improvement in sweating was seen following ten daily sessions of phonophoresis or iontophoresis. No adverse effects were reported. The clinical results achieved with treatment were maintained over 16 weeks of follow-up after the end of treatment. Percutaneous drug delivery techniques should be perceived as an option for the treatment of dermatologic conditions | Andrade et al. (2011) |
Immunosuppressives | ||
Investigated the topical transport of cyclosporin A using low-frequency ULS throughout rat skin | The enhanced skin accumulation of cyclosporin A by the combination of low-frequency ULS and chemical enhancers could help significantly to optimize the targeting of the drug without a concomitant increase of the systemic side effects | Liu et al. (2006) |
Evaluation of the efficacy of low-frequency sonophoresis (LFS) for treatment of alopecia areata, melasma, and solar lentigo | The study showed that LFS enhanced penetration of topic agents obtaining effects at the level of the epidermis, dermis, and appendages, giving better results in the treatment of some cosmetic skin disorders | Santoianni et al. (2004) |
Anticancer drugs | ||
Application of a method using ULS and nano-/microbubbles to cancer gene therapy using prodrug activation therapy | Dramatic reductions of the tumor size by a factor of four | Aoi et al. (2007) |
Investigation of competitive transport across the skin of 5-fluorouracil into coupling gel under the influence of ULS and heat-alone and Azone® enhancement | Ultrasonication produced a decrease in percutaneous drug penetration. This effect was due to the diffusive loss of the hydrophilic substance 5-fluorouracil from the skin surface | Meidan et al. (1999) |
Insulin | ||
To investigate the role of cavitation in transdermal insulin delivery | Results show that in agar gel, both insulin penetration depth and concentration only increased considerably in the presence of inertial cavitation, with up to a 40 % enhancement. In porcine skin the amount of fluorescent insulin was higher in the epidermis of those samples that were exposed to ULS compared to the control samples, but there was no significant increase in penetration distance | Feiszthuber et al. (2015) |
To determine if the 3 × 1 rectangular cymbal array performs significantly better than the 3 × 3 circular array for glucose reduction in hyperglycemic rabbits | Using the rectangular cymbal array, the glucose decreased faster to a level of −200.8 ± 5.9 mg/dL after 90 min | Luis et al. (2007) |
To demonstrate ultrasonic transdermal delivery of insulin in vivo using rabbits | For the ULS-insulin group, the glucose level was found to decrease to −132.6 ± 35.7 mg/dL from the initial baseline in 60 min | |
To demonstrate the feasibility of ULS-mediated transdermal delivery of insulin in vivo using rats with a novel, low profile two-by-two ULS array based on the “cymbal” transducer | For the 60-min ULS exposure group, the glucose level was established to decrease from the baseline to −267.5 ± 61.9 mg/dL in 1 h. Moreover, to study the effects of ULS exposure time on insulin delivery, the 20-min group had essentially the same result as the 60-min exposure at a similar intensity | |
Corticosteroids | ||
Determination of the effect of ULS on the transcutaneous absorption of dexamethasone | A sonophoretic effect occurred with dexamethasone when its application saturated the skin | Saliba et al. (2007) |
To determine if ULS enhances the diffusion of transdermal applied corticosteroids | The effects of sonophoresed dexamethasone can be measured in terms of reduced collagen deposition as far down as the subcutaneous tissue but not in the submuscular or subtendinous tissue | Byl et al. (1993) |
Comparison of effectiveness of 0.4 % dexamethasone sodium phosphate (DEX-P) sonophoresis (PH) with 0.4 % DEX-P iontophoresis (ION) therapy in the management of patients with knee joint osteoarthritis | Significant improvement in total WOMAC scores was observed in 15 (60 %) and 16 (64 %) patients in the PH and ION groups, respectively, indicating no significant difference in the improvement rate | Akinbo et al. (2007) |
Designing a sonophoretic drug delivery system to enhance the triamcinolone acetonide (TA) permeability | The highest permeation of TA was observed under the ULS treatment conditions of low-frequency, high-intensity, and continuous mode | Yang et al. (2006) |
Cardiotonics | ||
The sonophoresis of digoxin in vitro through human and hairless mouse skin | There was no enhancement of digoxin absorption across human skin by ULS | Machet et al. (1996) |
Vasodilators | ||
Skin penetration enhancement effect of ULS on methyl nicotinate in ten healthy human volunteers | ULS treatment applied prior to methyl nicotinate led to enhanced percutaneous absorption of the drug | McElnay et al. (1993) |
Hormones | ||
Effect of permeation enhancers and application of low-frequency (LUS) and high-frequency (HUS) ULS on testosterone (TS) transdermal permeation after application of testosterone solid lipid microparticles (SLM) | Skin contact to HUS or LUS before appliance of 1 % dodecylamine for 30 min had no superior improvement effect over appliance of either LUS or HUS alone. Application of drug-loaded SLM presented skin defense against the irritation result produced by TS and 1 % DA | El-Kamel et al. (2008) |
Cicatrizants | ||
The effectiveness of sonophoresis on the delivery of high-molecular-weight hyaluronan (HA) into the synovial membrane using an animal model of osteoarthritis | Synovial fluid analysis revealed increased absorption, and fluorescence microscopy showed deeper penetration of both HA1000 and HA3000 | Park et al. (2005) |
Calcein | ||
The skin permeation clearance of model hydrophilic solutes, calcein-labeled dextrans, across the skin under the influence of ULS | Good correlations were observed between the 3H2O flux and solute clearances, and, unexpectedly, the slope values obtained from linear regression of the plots were consistent for all solutes examined | Morimoto et al. (2005) |
Oligonucleotides | ||
Assessment of the potential of low-frequency ULS in delivering therapeutically significant quantities of antisense oligonucleotides into the skin | Microscopic evaluations using revealed heterogeneous penetration into the skin | Tezel et al. (2004) |
Stimulants | ||
The effect of low-frequency sonophoresis on fentanyl and caffeine permeation through human and hairless rat skin | Discontinuous ULS mode was found to be more effective in increasing transdermal diffusion of fentanyl, while transdermal transportation of caffeine was improved by both continuous and pulsed mode | |
To optimize sonophoresis protocol for studying in vitro transdermal drug delivery of caffeine | It was found that the best regimen for caffeine skin permeation was a concurrent 5 min, pulsed mode of 10 % duty cycle, and at an intensity of 0.37 W/cm2 | Sarheed and Abdul Rasool (2011) |
Calcium | ||
Manipulation of the Ca2+ content of the upper epidermis by sonophoresis across hairless mouse SC | Sonophoresis at 15 MHz did not alter barrier function | Menon et al. (1994) |
Panax notoginseng | ||
Effect of a therapeutic ULS coupled with a Panax notoginseng gel for medial collateral ligament repair in rats | This study reveals a helpful ultrasonic effect of Panax notoginseng extract for improving the strength of ligament repair | Ng and Wong (2008) |
Ocular drug release | ||
To demonstrate that ULS enhances sodium fluorescein corneal permeability in rabbit | ULS enhanced, by up to ten times, the corneal permeability to different compounds such as beta-blockers and fluorescein | Zderic et al. (2004a) |
Enhancement of corneal permeability of different drugs for treatment of glaucoma | In all the cases, the permeability of rabbit cornea increased by different magnitudes (2.6 times for atenolol, 2.8 for carteolol, 1.9 for timolol, and 4.4 times for betaxolol) after 60-min ULS exposure in vitro | Zderic et al. (2004b) |
Nail drug release | ||
Design of a novel ULS-mediated drug delivery system for treatment of onychomycosis | Current treatments for onychomycosis take a long time to result in nail healing, thus making this ULS-mediated device a promising alternative | Abadi and Zderic (2011) |
Table 3.6
Experimental conditions for different researchers to study transdermal, ungual, and ocular delivery of drugs by sonophoresis
Drug | Experimental settings used by different researchers for topical transdermal drug release | Ref. |
|---|---|---|
Lidocaine | In good physical shape volunteers Rabbit skin Different drug concentrations and frequencies (250–100 kHz) Comparison of pulsed and continuous ULS | |
Procaine hydrochloride | Cultured Madin-Darby Canine Kidney (MDCK) epithelial cell a model Constant irradiation of 1.0 W/cm2 | Hehn and Moll (1996) |
Piroxicam | Cellulose film and rabbit skin 0.5–3.0 W/cm2 | Meshali et al. (2008) |
Ibuprofen | Cellulose film and rabbit membrane 0.5–3.0 W/cm2 | Meshali et al. (2008) |
Diclofenac sodium | Cellulose film and rabbit membrane 0.5–3.0 W/cm2 Humans Polyamidoamine dendrimers together with sonophoresis | |
Indomethacin | Rat skin Range of intensities (0.25, 0.5, 0.75, and 1 W/cm2) Time 5–20 min | Miyazaki et al. (1992) |
Ketorolac tromethamine | Rat skin Continuous mode, intensity of 1–3 W/cm2, and a frequency of 1 MHz for 30 min | |
Ketoprofen | Humans Pulse mode of ULS and an intensity of 0.8 W/cm2 Hairless rat skin Frequency of 20 kHz | |
Flufenamic acid | Human skin Range of intensities (up to 1.5 W/cm2) Time ULS energy between 5 and 30 min | Hippius et al. (1998) |
Lychnophora pinaster extracts | Transdermal sonophoresis in rat paws of gel with lupeol and quercetin | Abreu et al. (2013) |
Arnica montana, capsaicin, methyl salicylate
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