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Phonophoresis, also known as sonophoresis, is the method of using ultrasound waves to increase skin permeability in order to improve the effectiveness of transdermal drug delivery. This method intersects drug delivery and ultrasound therapy. Phonophoresis is able to achieve specific and efficient delivery of drugs that are delivered through the skin and ensure that the drug reaches the targeted area in the tissue environment. By assisting transdermal drug delivery, phonophoresis can help patients experience painless, minimal risk, and effective treatment.


The primary purpose of phonophoresis is to assist in transdermal drug delivery, usually with the help of a coupling agent or medium.[1][2][3][4] One of the major obstacles to transdermal drug delivery is permeating the skin to reach a targeted area within the body.[1][2][3][4][5][6][7][8][9][10] The stratum corneum[1][2][3][4][5][7][8][9][10][11] is the layer of skin that prevents foreign substances from penetrating the body. This results in decreased permeability of the skin, which prevents effective drug delivery.[1][2][3][4][5][6][7][8][9][10][11] Efforts to use phonophoresis are due to the interest in transdermal drug delivery. Transdermal drug delivery is beneficial because of patient compliance,[7] the ability to avoid digestive system degradation,[1] and the ability to use drugs with short half-lives.[3]

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Treatment Methods[edit]

Phonophoresis can be performed using two main methods. The first is simultaneous treatment, where the drug can be applied at the same time as the ultrasound.[1][2][3][4][7] The second method is pretreatment, where the ultrasound is used briefly before drug delivery.[1][2][3][4][7] This ensures that the skin is permeable prior to the drug being applied.

Cavitation is important in understanding how to increase skin permeability through ultrasound.[1][3][4][7][11] When using an ultrasound, cavities will develop due to the pressure change. Stable cavitation describes repetitive oscillations of a cavity bubble, while inertial cavitation describes the collapse of a cavity bubble.[1][7][11] If the developed cavities fall apart, the effect on the stratum corneum lipids will increase the permeability of the skin.[3][11] These areas of increased permeability are often called localized transport regions, where there is lower electrical resistivity.[2] One potential method to take advantage of cavitation is the use of a cavitation seed at the surface of the skin.[6] Another potential method is to use ultrasound- responsive liquid-core nuclei (URLN).[11]


Low frequency ultrasound is seen as the optimal level of ultrasound frequency. This is typically characterized as 20 to 100 kHz (sometimes 18 to 100 kHz).[1][2][3][7] Low frequency can achieve optimal skin permeability because cavitation is more likely to occur at low frequencies than high frequencies.[1][3][4][7][11] For reference, high frequency ultrasound is typically in the range of 1 to 3 MHz.[1]

Coupling Agents[edit]

Coupling agents help the function of the ultrasound.[1][2][3][4] The physical component of the drug is also important in allowing the ultrasound to better facilitate delivery.[3] The drug should be able to work together with the coupling agent or can serve as the coupling agent.[3] One particular application of a coupling gel agent working with a drug is described in a 2019 study that utilizes the drug diclofenac in coordination with thiocolchioside gel to treat patients who suffer from acute lower back pain.[5] An application of a drug serving as a coupling agent is the use of piroxicam gel mixtures and dexamethasone sodium phosphate gel mixtures to treat patients who suffer from carpal tunnel syndrome.[12]


Physical Conditions[edit]

Phonophoresis is primarily used to address physical conditions, as phonophoresis would be used with drug delivery through the skin surface. Various conditions that can be addressed include cervical spine pain,[13] acute lower back pain,[5] carpal tunnel syndrome,[12] muscle injury,[14] rheumatoid arthritis,[8] and venous thrombosis.[10] Examples of drugs that have been used with sonophoresis include hydrocortisone, mannitol, dexamethasone, and lidocaine.[3]

Several products have been marketed to use phonophoresis for transdermal drug delivery. Examples include the U-strip, SonoPrep, and Sonoderm Technology.[3]

Other Uses[edit]

A future application of phonophoresis is to use it with vaccines, as phonophoresis is a less painful and more appealing alternative to needles.[2][3][7] Another potential use is in cancer therapeutics; one such application that has been explored is the delivery of cisplatin for patients who have cervical cancer.[15] Going forward, genetic skin diseases and wound healing can also be assisted with phonophoresis.[3] An example of a wound healing application is the use of phonophoresis to assist microneedles in delivering drugs to treat keloids.[9]



Phonophoresis is relatively safe, which makes it appealing to clinicians. At an optimal frequency, phonophoresis will have minimal to no risk and patients will not experience pain. How long the ultrasound is used, and the intensity of the ultrasound is also important to consider.[3] One concern is how long phonophoresis can be used before it poses a risk to patient health.[4] The heat that is emitted from ultrasound use can also be damaging to the surface of the skin,[4] and cavitation can potentially lead to tissue damage.[4] Nanoparticle toxicity is another potential risk.[4]


  1. ^ a b c d e f g h i j k l m Machet, L., & Boucaud, A. (2002). "Phonophoresis: efficiency, mechanisms and skin tolerance". International Journal of Pharmaceutics. 243 (1–2): 1–15. doi:10.1016/S0378-5173(02)00299-5. PMID 12176291.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b c d e f g h i j Ogura, M., Paliwal, S., & Mitragotri, S. (2008). "Low-frequency sonophoresis: Current status and future prospects". Advanced Drug Delivery Reviews. 60 (10): 1218–1223. doi:10.1016/j.addr.2008.03.006. PMID 18450318.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ a b c d e f g h i j k l m n o p q r s Rao, R., & Nanda, S. (2009). "Sonophoresis: recent advancements and future trends". Journal of Pharmacy and Pharmacology. 61 (6): 689–705. doi:10.1211/jpp.61.06.0001. PMID 19505359. S2CID 4247361.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b c d e f g h i j k l m Seah, B., & Teo, B. (2018). "Recent advances in ultrasound-based transdermal drug delivery". International Journal of Nanomedicine. 13: 7749–7763. doi:10.2147/IJN.S174759. PMC 6251463. PMID 30538456.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ a b c d e Altan, L., Kasapoglu Aksoy, M., & Kosegil Ozturk, E. (2019). "Efficacy of diclofenac & thiocolchioside gel phonophoresis comparison with ultrasound therapy on acute low back pain; a prospective, double-blind, randomized clinical study". Ultrasonics. 91: 201–205. doi:10.1016/j.ultras.2018.08.008. PMID 30139568. S2CID 52076491.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b c Donghee, P., Jongho, W., Unchul, S., Hyeon, P., Gillsoo, S., Jiyoung, J., Hyunjin, P., Chul Woo, K., & Jong Bum, Seo. (2019). "Transdermal Drug Delivery Using a Specialized Cavitation Seed for Ultrasound". IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 66 (6): 1057–1064. doi:10.1109/TUFFC.2019.2907702. PMID 30946663. S2CID 96432587.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ a b c d e f g h i j k Lavon, I., & Kost, J. (2004). "Ultrasound and transdermal drug delivery". Drug Discovery Today. 9 (15): 670–676. doi:10.1016/S1359-6446(04)03170-8. PMID 15279850.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ a b c d Vaidya, J., & Shende, P. (2020). "Potential of Sonophoresis as a Skin Penetration Technique in the Treatment of Rheumatoid Arthritis with Transdermal Patch". AAPS PharmSciTech. 21 (5): 180. doi:10.1208/s12249-020-01725-w. PMID 32601758. S2CID 220261137.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ a b c d Yang, Y., Xia, L., Ning, X., Hu, T., Xu, C., & Liu, W. (2021). "Enhanced Drug Permeation into Human Keloid Tissues by Sonophoresis-Assisted Microneedling". SLAL Technology. 26 (6): 660–666. doi:10.1177/24726303211024568. PMID 34219535. S2CID 235732832.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ a b c d Zhai, H., Zhang, C., Ou, H., & Chen, M. (2021). "Transdermal delivery of heparin using low- frequency sonophoresis in combination with sponge spicules for venous thrombosis treatment". Biomaterials Science. 9 (16): 5612–5625. doi:10.1039/D1BM00703C. PMID 34254062. S2CID 235809367.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ a b c d e f g Donghee, P., Jongho, W., Gyounjung, L., Yongheum, L., Chul-Woo, K., & Jongbum, Seo. (2022). "Sonophoresis with ultrasound-responsive liquid-core nuclei for transdermal drug delivery". Skin Research and Technology. 28 (2): 291–298. doi:10.1111/srt.13129. PMID 35034386. S2CID 247599798.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ a b Boonhong, J., & Thienkul, W. (2019). "Effectiveness of Phonophoresis Treatment in Carpal Tunnel Syndrome: A Randomized Double-blind, Controlled Trial". PM&R. 12 (1): 8–15. doi:10.1002/pmrj.12171. PMID 31006972. S2CID 128352578.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Aiyegbusi, A.I., Sanni, H.O., & Akinbo, S.R. (2019). "Intrasound Therapy: An Effective Alternative to Sodium Diclofenac Phonophoresis in the Management of Mechanical Chronic Cervical Spine Pain". Journal of Applied Sciences and Environmental Management. 23 (2): 371. doi:10.4314/jasem.v23i2.26. S2CID 86999653.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Haupenthal, D., Zortea, D., Zaccaron, R., Silveira, G., Correa, M., Mendes, C., Casagrande, L., Duarte, M., Pinho, R., Feuser, P., Avila, R., and Silveira, P. (2020). "Effects of phonophoresis with diclofenac linked gold nanoparticles in model of traumatic muscle injury". Materials Science and Engineering. 110: 110681. doi:10.1016/j.msec.2020.110681. PMID 32204109. S2CID 212931024.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Ma, S., Liu, C., Zhang, T., Jiang, L., & Wang, R. (2020). "Sonophoresis Enhanced Transdermal Delivery of Cisplatin in the Xenografted Tumor Model of Cervical Cancer". OncoTargets and Therapy. 13: 889–902. doi:10.2147/OTT.S238126. PMC 6996214. PMID 32099393.{{cite journal}}: CS1 maint: multiple names: authors list (link)