Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Advances in Ultrasound Mediated Transdermal Drug Delivery

Author(s): Saloni Daftardar, Rabin Neupane, Sai HS. Boddu*, Jwala Renukuntla and Amit K. Tiwari

Volume 25, Issue 4, 2019

Page: [413 - 423] Pages: 11

DOI: 10.2174/1381612825666190211163948

Price: $65

Abstract

Low frequency ultrasound-assisted drug delivery has been widely investigated as a non-invasive method to enhance the transdermal penetration of drugs. Using this technique, a brief application of ultrasound is used to permeabilize skin for a prolonged time. In this review, an overview on ultrasound is detailed to help explain the parameters that could be modulated to obtain the desired ultrasound parameters for enhanced transdermal drug delivery. The mechanisms of enhancement and the latest developments in the area of ultrasound-assisted transdermal drug delivery are discussed. Special emphasis is placed on the effects of ultrasound when used in combination with microneedles, electroporation and iontophoresis, and penetration enhancers. Further, this review summarizes the effect of ultrasound on skin integrity and the regulatory requirements for commercialization of the ultrasound based transdermal delivery instruments.

Keywords: Ultrasound, low frequency ultrasound-assisted drug delivery, ultrasound bioeffects, cavitation, transducers, skin integrity, regulations.

[1]
Martini S. An overview of ultrasound. in Sonocrystallization of Fats2013 , Springer p 7-16.
[2]
Oberli MA, Schoellhammer CM, Langer R, Blankschtein D. Ultrasound-enhanced transdermal delivery: recent advances and future challenges. Ther Deliv 2014; 5(7): 843-57.
[3]
Hoogland R. Ultrasound therapy1986 Enraf-Nonius.
[4]
Boucaud A, Machet L, Arbeille B, et al. In vitro study of low-frequency ultrasound-enhanced transdermal transport of fentanyl and caffeine across human and hairless rat skin. Int J Pharm 2001; 228(1-2): 69-77.
[5]
Kost J, Levy D, Langer R. Ultrasound as a transdermal enhancer. Top Drug Deliv Formul 1989; 42: 603-32.
[6]
Mutoh M, Ueda H, Nakamura Y, et al. Characterization of transdermal solute transport induced by low-frequency ultrasound in the hairless rat skin. J Control Release 2003; 92(1-2): 137-46.
[7]
Cagnie B1. Vinck E, Rimbaut S, Vanderstraeten G. Phonophoresis versus topical application of ketoprofen: comparison between tissue and plasma levels. Phys Ther 2003; 83(8): 707-12.
[8]
Jacobsen F, Juhl PM. Fundamentals of General Linear Acoustics2013 : John Wiley & Sons.
[9]
Fahy FJ, Salmon V. Sound intensity1990, ASA.
[10]
FDA US. Guidance for Industry and FDA Staff Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers. Rockville, MD: FDA 2008.
[11]
Middleton W, Kurtz A, Hertzberg B. Practical physics Ultrasound: the requisites 2nd ed St Louis: Mosby, 2004 4: p 18-21.
[12]
Lieu D. Ultrasound physics and instrumentation for pathologists. Arch Pathol Lab Med 2010; 134(10): 1541-56.
[13]
Tressler JF, Cao W, Uchino K, Newnham RE. Finite element analysis of the cymbal-type flextensional transducer. IEEE Trans Ultrason Ferroelectr Freq Control 1998; 45(5): 1363-9.
[14]
Mulvihill ML, Snook KA, Van Ess IR, et al. Ultrasonic transducer and transdermal delivery system2016 Google Patents US20160303360A1
[15]
Jabbari N, Asghari MH, Ahmadian H, Mikaili P. Developing a commercial air ultrasonic ceramic transducer to transdermal insulin delivery. J Med Signals Sens 2015; 5(2): 117-2.
[16]
Huan H, Gao C, Liu L, Sun Q, Zhao B, Yan L. Research of ultrasound-mediated transdermal drug delivery system using cymbal-type piezoelectric composite transducer. Int J Thermophys 2015; 36(5-6): 1312-9.
[17]
Redding Jr B.K.. Method and apparatus for measuring the dose remaining upon a transdermal drug delivery device 2017. Google Patents US 15/323,641
[18]
Redding Jr B.K.. Systems and Methods for Enhancing the Delivery of Compounds to Skin Pores using Ultrasonic Waveforms 2018. Google Patents US 15/623,020
[19]
Watkinson AC. Transdermal and topical drug delivery todayTopical and Transdermal Drug Delivery: Principles and Practice 2012: 357-366
[20]
O’Brien Jr W.D.. Ultrasound–biophysics mechanisms. Prog Biophys Mol Biol 2007; 93(1-3): 212-55.
[21]
Polat BE, Hart D, Langer R, Blankschtein D. Ultrasound-mediated transdermal drug delivery: mechanisms, scope, and emerging trends. J Control Release 2011; 152(3): 330-48.
[22]
Byl NN. The use of ultrasound as an enhancer for transcutaneous drug delivery: phonophoresis. Phys Ther 1995; 75(6): 539-53.
[23]
Bommannan D, Okuyama H, Stauffer P, Guy RH, Sonophoresis I. The use of high-frequency ultrasound to enhance transdermal drug delivery. Pharm Res 1992; 9(4): 559-64.
[24]
Boucaud A, Montharu J, Machet L, et al. Clinical, histologic, and electron microscopy study of skin exposed to low‐frequency ultrasound. Anat Rec 2001; 264(1): 114-9.
[25]
Simonin J-P. On the mechanisms of in vitro and in vivo phonophoresis. J Control Release 1995; 33(1): 125-41.
[26]
Tang H, Wang CC, Blankschtein D, Langer R. An investigation of the role of cavitation in low-frequency ultrasound-mediated transdermal drug transport. Pharm Res 2002; 19(8): 1160-9.
[27]
Suslick KS. The chemical effects of ultrasound. Scientific American 1989; 260(2): 80-6.
[28]
Crum LA, Mason TJ, Reisse JL, Suslick KS. Sonochemistry and SonoluminescenceVol 524 2013 Springer Science & Business Media.
[29]
Gaertner W. Frequency dependence of ultrasonic cavitation. J Acoust Soc Am (JASA) 1954; 26(6): 977-80.
[30]
Ueda H, Mutoh M, Seki T, Kobayashi D, Morimoto Y. Acoustic cavitation as an enhancing mechanism of low-frequency sonophoresis for transdermal drug delivery. Biol Pharm Bull 2009; 32(5): 916-20.
[31]
Tezel A, Mitragotri S. Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers during low-frequency sonophoresis. Biophys J 2003; 85(6): 3502-12.
[32]
Meidani AN, Hasan M. Mathematical and physical modelling of bubble growth due to ultrasound. Appl Math Model 2004; 28(4): 333-51.
[33]
Mitragotri S, Edwards DA, Blankschtein D, Langer R. A mechanistic study of ultrasonically‐enhanced transdermal drug delivery. J Pharm Sci 1995; 84(6): 697-706.
[34]
Mitragotri S, Blankschtein D, Langer R. Ultrasound-mediated transdermal protein delivery. Science 1995; 269(5225): 850-3.
[35]
Clarke L, Edwards A, Graham E. Acoustic streaming-an in vitro study. Ultrasound Med Biol 2003; 29(5): S214-5.
[36]
Zhang N, Wu Y, Xing R, Xu B, Guoliang D, Wang P. Effect of Ultrasound-Enhanced Transdermal Drug Delivery Efficiency of Nanoparticles and Brucine. BioMed Res Int 2017; 2017: 1-8.
[37]
Terahara T, Mitragotri S, Kost J, Langer R. Dependence of low-frequency sonophoresis on ultrasound parameters; distance of the horn and intensity. Int J Pharm 2002; 235(1-2): 35-42.
[38]
Mitragotri S, Farrell J, Tang H, Terahara T, Kost J, Langer R. Determination of threshold energy dose for ultrasound-induced transdermal drug transport. J Control Release 2000; 63(1-2): 41-52.
[39]
Merino G, Kalia YN, Delgado-Charro MB, Potts RO, Guy RH. Frequency and thermal effects on the enhancement of transdermal transport by sonophoresis. J Control Release 2003; 88(1): 85-94.
[40]
Herwadkar A, Sachdeva V, Taylor LF, Silver H, Banga AK. Low frequency sonophoresis mediated transdermal and intradermal delivery of ketoprofen. Int J Pharm 2012; 423(2): 289-96.
[41]
Laugier P, G. Haïat. Introduction to the physics of ultrasound. In: Bone Quantitative Ultrasound2011 Springer . 29-45.
[42]
Tachibana K, Tachibana S. Transdermal delivery of insulin by ultrasonic vibration. J Pharm Pharmacol 1991; 43(4): 270-1.
[43]
Smith NB, Lee S, Maione E, Roy RB, McElligott S, Shung KK. Ultrasound-mediated transdermal transport of insulin in vivo through human skin using novel transducer designs. Ultrasound Med Biol 2003; 29(2): 311-7.
[44]
Tachibana K. Transdermal delivery of insulin to alloxan-diabetic rabbits by ultrasound exposure. Pharm Res 1992; 9(7): 952-4.
[45]
Zorec B, Jelenc J, Miklavčič D, Pavšelj N. Ultrasound and electric pulses for transdermal drug delivery enhancement: Ex vivo assessment of methods with in vivo oriented experimental protocols. Int J Pharm 2015; 490(1-2): 65-73.
[46]
Slayton MH. Methods and Systems for Ultrasound Assisted Delivery of a Medicant to Tissue 2018. Google Patents EP3265168A1
[47]
Tezel A1. Sens A, Tuchscherer J, Mitragotri S. Frequency dependence of sonophoresis. Pharm Res 2001; 18(12): 1694-700.
[48]
Tezel A, Dokka S, Kelly S, Hardee GE, Mitragotri S. Topical delivery of anti-sense oligonucleotides using low-frequency sonophoresis. Pharm Res 2004; 21(12): 2219-25.
[49]
Zimon RL, Lerman G, Elharrar E, et al. Ultrasound targeting of Q-starch/miR-197 complexes for topical treatment of psoriasis. J Control Release 2018; 284: 103-11.
[50]
Kline-Schoder A, Lee Z, Zderic V. Ultrasound-enhanced drug delivery for treatment of onychomycosis. J Ultrasound Med 2018; 37(7): 1743-52.
[51]
Gupta J, Prausnitz MR. Recovery of skin barrier properties after sonication in human subjects. Ultrasound Med Biol 2009; 35(8): 1405-8.
[52]
Schoellhammer CM1, Polat BE, Mendenhall J, et al. . Rapid skin permeabilization by the simultaneous application of dual-frequency, high-intensity ultrasound. J Control Release 2012; 163(2): 154-60.
[53]
Schoellhammer CM. Srinivasan S2, Barman R, et al. Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs. J Control Release 2015; 202: 93-100.
[54]
Han Y, Zhao Q, Yu D, Liu Z. Treatment of chest wall tuberculosis with transdermal ultrasound-mediated drug delivery. Exp Ther Med 2015; 9(4): 1433-7.
[55]
Bhatnagar S, Kwan JJ, Shah AR, Coussios CC, Carlisle RC. Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines. J Control Release 2016; 238: 22-30.
[56]
Soto F, Mishra RK, Chrostowski R, Martin A, Wang J. Epidermal Tattoo Patch for Ultrasound-Based Transdermal Microballistic Delivery. In: Advanced. Mater Technol 2017; 2(12): 1700210.
[57]
Soto F, Jeerapan I, Silva‐López C, et al. Noninvasive Transdermal Delivery System of Lidocaine Using an Acoustic Droplet-Vaporization Based Wearable Patch 2018. 1803266.
[58]
Nguyen H, Banga AJP. Electrically and Ultrasonically Enhanced Transdermal Delivery of Methotrexate. Pharmaceutics 2018; 10(3): 117.
[59]
Shirouzu K, Nishiyama T, Hikima T, Tojo K. Synergistic effect of sonophoresis and iontophoresis in transdermal drug delivery. J Chem Eng of Jpn 2008; 41(4): 300-5.
[60]
Chapin N, Hung M, Larsen W, Pramil V. Optimization of Transdermal Drug Delivery by Hydrogel-Enhanced Sonophoresis 2015.
[61]
Chen B, Wei J, Iliescu C. Sonophoretic enhanced microneedles array (SEMA)-Improving the efficiency of transdermal drug delivery. Sens Actuators B Chem 2010; 145(1): 54-60.
[62]
Petchsangsai M, Rojanarata T, Opanasopit P, Ngawhirunpat T. The combination of microneedles with electroporation and sonophoresis to enhance hydrophilic macromolecule skin penetration. Biol Pharm Bull 2014; 37(8): 1373-82.
[63]
Park D, Yoon J, Park J, Jung B, Park H, Seo J. Transdermal drug delivery aided by an ultrasound contrast agent: an in vivo experimental study. Open Biomed Eng J 2010; 4: 56-62.
[64]
Kost J, Pliquett U, Mitragotri S, Yamamoto A, Langer R, Weaver J. Synergistic effect of electric field and ultrasound on transdermal transport. Pharm Res 1996; 13(4): 633-8.
[65]
Zorec B, Zupančič Š, Kristl J, Pavšelj N. Combinations of nanovesicles and physical methods for enhanced transdermal delivery of a model hydrophilic drug. Eur J Pharm Sci 2018; 127: 387-97.
[66]
Terentyuk GS, Genina EA, Bashkatov AN, Ryzhova MV. Use of fractional laser microablation and ultrasound to facilitate the delivery of gold nanoparticles into skin in vivo. Quantum Electron 2012; 42(6): 471.
[67]
Mitragotri S, Ray D, Farrell J, et al. Synergistic effect of low‐frequency ultrasound and sodium lauryl sulfate on transdermal transport. J Pharm Sci 2000; 89(7): 892-900.
[68]
Huang B, Dong WJ, Yang GY, Wang W, Ji CH, Zhou FN. Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac. Drug Des Devel Ther 2015; 9: 3867-76.
[69]
Manikkath J, Manikkath A, Shavi GV, Bhat K, Mutalik S. Low frequency ultrasound and PAMAM dendrimer facilitated transdermal delivery of ketoprofen. J Drug Deliv Sci Technol 2017; 41: 334-43.
[70]
Pereira TA, Ramos DN, Lopez RF. Hydrogel increases localized transport regions and skin permeability during low frequency ultrasound treatment. Sci Rep 2017; 7: 44236.
[71]
Yamashita N, Tachibana K, Ogawa K, Tsujita N, Tomita A. Scanning electron microscopic evaluation of the skin surface after ultrasound exposure. Anat Rec 1997; 247(4): 455-61.
[72]
Wu J, Chappelow J, Yang J, Weimann L. Defects generated in human stratum corneum specimens by ultrasound. Ultrasound Med Biol 1998; 24(5): 705-10.
[73]
Mitragotri S1. Blankschtein D, Langer R. Transdermal drug delivery using low-frequency sonophoresis. Pharm Res 1996; 13(3): 411-20.
[74]
Singer AJ, Homan CS, Church AL, McClain SA. Low-frequency sonophoresis: Pathologic and thermal effects in dogs. Acad Emerg Med 1998; 5(1): 35-40.
[75]
Manikkath J, Hegde AR, Kalthur G, Parekh HS, Mutalik S. Influence of peptide dendrimers and sonophoresis on the transdermal delivery of ketoprofen. Int J Pharm 2017; 521(1-2): 110-9.
[76]
Wolloch L, Kost J. The importance of microjet vs. shock wave formation in sonophoresis. J Control Release 2010; 148(2): 204-11.
[77]
Kasetvatin C, Rujivipat S, Tiyaboonchai W. Combination of elastic liposomes and low frequency ultrasound for skin permeation enhancement of hyaluronic acid. Colloids Surf B Biointerfaces 2015; 135: 458-64.
[78]
Park D, Ryu H, Kim HS, et al. Sonophoresis using ultrasound contrast agents for transdermal drug delivery: an in vivo experimental study. Ultrasound Med Biol 2012; 38(4): 642-50.
[79]
Han T, Das DB. Permeability enhancement for transdermal delivery of large molecule using low-frequency sonophoresis combined with microneedles. J Pharm Sci 2013; 102(10): 3614-22.
[80]
Duck FA. Safety standards and regulations: the manufacturers’ responsibilities.in The Safe Use of Ultrasound in Medical Diagnosis 2000. British Institute of Radiology London ; pp. 94-101.
[81]
Haar Gt. Ultrasonic imaging: safety considerations. Interface Focus 2011; 1(4): 686-97.
[82]
Haar Gt. Ultrasonic imaging: safety considerations Interface focus, 2011: p rsfs20110029.
[83]
Food, US and A Drug Information for manufacturers seeking marketing clearance of diagnostic ultrasound systems and transducers. Rockville, MD: Center for Devices and Radiological Health, US Food and Drug Administration 1997.
[84]
Fellinger K, Schmid J. Klinik und Therapie des chronischen Gelenkrheumatismus. JAMA 1954; 155(3): 322.
[85]
Watkinson AC, Kearney MC, Quinn HL, Courtenay AJ, Donnelly RF. Future of the transdermal drug delivery market--have we barely touched the surface? Expert Opin Drug Deliv 2016; 13(4): 523-32.
[86]
Wang HL, Fan PF, Guo XS, Tu J, Ma Y, Zhang D. Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vivo. Chin Phys B 2016; 25(12): 124314.
[87]
Lopez RF, Seto JE, Blankschtein D, Langer R. Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate. Biomaterials 2011; 32(3): 933-41.
[88]
Meshali MM, Abdel-Aleem HM, Sakr FM, Nazzal S, El-Malah Y. In vitro phonophoresis: effect of ultrasound intensity and mode at high frequency on NSAIDs transport across cellulose and rabbit skin membranes. Pharmazie 2008; 63(1): 49-53.
[89]
Aldwaikat M, Alarjah M. Investigating the sonophoresis effect on the permeation of diclofenac sodium using 3D skin equivalent. Ultrason Sonochem 2015; 22: 580-7.
[90]
Meshali M, Abdel-Aleem H, Sakr F, Nazzal S, El-Malah Y. Effect of gel composition and phonophoresis on the transdermal delivery of ibuprofen: in vitro and in vivo evaluation. Pharm Dev Technol 2011; 16(2): 93-101.
[91]
Escobar-Chávez JJ, Bonilla-Martínez D, Villegas-González MA, Rodríguez-Cruz IM, Domínguez-Delgado CL. The use of sonophoresis in the administration of drugs throughout the skin. J Pharm Pharm Sci 2009; 12(1): 88-115.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy