Abstract
Several strategies have been studied in the last decades in order to improve drug transport across the skin. Transdermal drug delivery systems represent a huge business opportunity for pharmaceutical industries. Although chemical enhancers have proven to be effective in promoting the transport of molecules throughout skin, the combination of chemical and physical/mechanical enhancers has shown a synergistic effect in most of the cases. This chapter reviews the enhancement effect of the combined use of sonophoresis, electroporation, and microneedles with chemical enhancers.
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References
Alexander A, Dwivedi S, Ajazuddin, Giri TK, Saraf S, Saraf SH, Tripathi DK (2012) Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J Control Release 164:26–40
Alvarez-Roman R, Merriono G, Kalia YN, Naik A, Guy R (2003) Skin permeability enhancement by low-frequency sonophoresis – lipid extraction and transport pathways. J Pharm Sci 92:1138–1146
Arora A, Prausnitz MR, Mitragotri S (2008) Micro-scale devices for transdermal drug delivery. Int J Pharm 364:227–236
Azagury A, Khoury L, Adato Y, Wolloch L, Ariel I, Hallak M, Kost J (2015) The synergistic effect of ultrasound and chemical penetration enhancers on chorioamnion mass transport. J Control Release 200:35–41
Badkar AV, Betageri GV, Hofmann GA, Banga AK (1999) Enhancement of transdermal iontophoretic delivery of a liposomal formulation of colchicine by electroporation. Drug Deliv 6(2):111–115
Badran MM, Kuntsche J, Fahr A (2009) Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation. Eur J Pharm Sci 36:511–523
Banga AK (2011) Skin electroporation and its applications. CRC Press, Boca Raton
Becker S, Zorec B, Miklavcic D, Pavselj N (2014) Transdermal transport pathway creation: electroporation pulse order. Math Biosci 257:60–68
Becker SM, Kuznetsov AV (2008) Thermal in vivo skin electroporation pore development and charged macromolecule transdermal delivery: a numerical study of the influence of chemically enhanced lower lipid phase transition temperatures. Int J Heat Mass Transf 51(7–8):2060–2074
Bonner MC, Barry BW (2006) Combined chemical and electroporation methods of skin penetration enhancement. In: Touitou E, Barry BW (eds) Enhancement in drug delivery. CRC Press, Boca Raton
Boucaud A (2004) Trends in the use of ultrasound-mediated transdermal drug delivery. Drug Discov Today 9:827–828
Brown MB, Martin GP, Jones SA, Akomeah FK (2006) Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 13(3):175–187
Chen B, Wei J, Iliescu C (2010) Sonophoretic enhanced microneedles array (SEMA) – improving the efficiency of transdermal drug delivery. Sens Actuators B 145:54–60
Dahlan A, Alpar HO, Murdan S (2009) An investigation into the combination of low frequency ultrasound and liposomes on skin permeability. Int J Pharm 379:139–142
David N, Mahmood TA, Inventors, Kithera Biopharmaceuticals, Inc. Assignee (2010) Systems and methods for delivery of biologically active agents. WO 2010/056922 A2
Denet A-R, Vanbever R, Préat V (2004) Skin electroporation for transdermal and topical delivery. Adv Drug Deliv Rev 56:659–674
Essa EA, Bonner MC, Barry BW (2003) Electroporation and ultradeformable liposomes; human skin barrier repair by phospholipid. J Control Release 92(1–2):163–172
Essa EA, Bonner MC, Barry BW (2004) Electrically assisted skin delivery of liposomal estradiol; phospholipid as damage retardant. J Control Release 95(3):535–546
Fang J-Y, Hwang T-L, Huang Y-B, Tsai Y-H (2002) Transdermal iontophoresis of sodium nonivamide acetate V. Combined effect of physical enhancement methods. Int J Pharm 235:95–105
Frenkel V (2008) Ultrasound mediated delivery of drugs and genes to solid tumors. Adv Drug Deliv Rev 60:1193–1208
Gerstel MS, Place VA, Inventors, Alza Corporation (Palo Alto, CA) Assignee (1976) Drug delivery device. United States Patent US Patent 3 964 482
Haar G (2007) Therapeutic applications of ultrasound. Prog Biophys Mol Biol 93:111–129
Han T, Das DB (2013) Permeability enhancement for transdermal delivery of large molecule using low-frequency sonophoresis combined with microneedles. J Pharm Sci 102:3614–3622
Han T, Das DB (2015) Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. Eur J Pharm Biopharm 89:312–328
Henry S, McAllister DV, Allen MG, Prausnitz MR (1998) Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci 87:922–925
Herwadkar A, Banga AK (2012) Peptide and protein transdermal drug delivery. Drug Discov Today Technol 9:e147–e154
Higaki K, Amnuaikit C, Kimura T (2003) Strategies for overcoming the stratum corneum. Am J Drug Deliv 1(3):187–214
Hosseinkhani H, Tabata Y (2005) Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran. J Control Release 108:540–556
Husseini GA, Pitt WG (2008) Micelles and nanoparticles for ultrasonic drug and gene delivery. Adv Drug Deliv Rev 60:1137–1152
Ilic L, Gowrishankar TR, Vaughan TE, Herndon TO, Weaver JC (1999) Spatially constrained skin electroporation with sodium thiosulfate and urea creates transdermal microconduits. J Control Release 61(1–2):185–202
Ita K (2015) Transdermal delivery of heparin: physical enhancement techniques. Int J Pharm 496:240–249
Jiang G, Zhu D, Zan J, Ding F (2007) Transdermal drug delivery by electroporation: the effects of surfactants on pathway lifetime and drug transport. Chin J Chem Eng 15(3):397–402
Johnson M, Mitragotri S, Patel A, Blankschtein D, Langer R (1996) Synergistic effects of chemical enhancers and therapeutic ultrasound on transdermal drug delivery. J Pharm Sci 85:670–679
Joshi A, Raje J (2002) Sonicated transdermal transport. J Control Release 83:13–22
Kasetvatin Ch, Rujivipat S, Tiyaboonchai W (2015) Combination of elastic liposomes and low frequency ultrasound for skin permeation enhancement of hyaluronic acid. Colloids Surf B Biointerfaces 135:458–464
Khafagy E-S, Morishita M, Onuki Y, Takayama K (2007) Current challenges in non-invasive insulin delivery systems: a comparative review. Adv Drug Deliv Rev 59:1521–1546
Kim K, Choi SW, Kwak YH (2012) The effect of SonoPrep® on EMLA® cream application for pain relief prior to intravenous cannulation. Eur J Pediatr 171:985–988
Lavon I, Kost J (2004) Ultrasound and transdermal drug delivery. Drug Discov Today 9:670–676
Lavon I, Grossman N, Kost J (2005) The nature of ultrasound-SLS synergism during enhanced transdermal transport. J Control Release 107:484–494
Le L, Kost J, Mitragotri S (2000) Combined effect of low-frequency ultrasound and iontophoresis: applications for transdermal heparin delivery. Pharm Res 17:1151–1154
Lee SE, Choi KJ, Menon GK, Kim HJ, Choi EH, Ahn SK, Lee SH (2010) Penetration pathways induced by low-frequency sonophoresis with physical and chemical enhancers: iron oxide nanoparticles versus lanthanum nitrates. J Invest Dermatol 130:1063–1072
Liu H, Li S, Pan W, Wang Y, Han F, Yao H (2006) Investigation into the potential of low-frequency ultrasound facilitated topical delivery of Cyclosporine A. Int J Pharm 326(1–2):32–38
Lombry C, Dujardin N, Préat V (2000) Transdermal delivery of macromolecules using skin electroporation. Pharm Res 17(1):32–37
Lopez RFV, Seto JE, Blankschtein D, Langer R (2011) Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate. Biomaterials 32:933–941
Machet L, Boucaud A (2002) Phonophoresis: efficiency, mechanisms and skin tolerance. Int J Pharm 243:1–15
Mathur V, Satrawala Y, Rajput MS (2010) Physical and chemical penetration enhancers in transdermal drug delivery system. Asian J Pharm 4(3):173–183
Meidan VM, Walmsley AD, Irwin WJ (1995) Phonophoresis: is it a reality? Int J Pharm 118:129–149
Meidan V, Docker M, Wlamsley A, Irwin W (1998) Phonophoresis of hydrocortisone with enhancers: an acoustically defined model. Int J Pharm 170:157–168
Mitragotri S (2000) Synergistic effect of enhancers for transdermal drug delivery. Pharm Res 17(11):1354–1359
Mitragotri S (2004) Sonophoresis: a 50-year journey. Drug Discov Today 9:735–736
Mitragotri S (2013) Devices for overcoming biological barriers: the use of physical forces to disrupt the barriers. Adv Drug Deliv Rev 65(1):100–103
Mitragotri S, Kost J (2004) Low-frequency sonophoresis. Adv Drug Deliv Rev 56:589–601
Mitragotri S, Blankschtein D, Langer R (1995) Ultrasound-mediated transdermal protein delivery. Science 269:850–853
Mitragotri S, Blankschtein D, Langer R (1996) Transdermal drug delivery using low-frequency sonophoresis. Pharm Res 13:411–420
Mitragotri S, Ray D, Farrell J, Tang H, Yu B, Kost J, Blankschtein D, Langer R (2000) Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport. J Pharm Sci 89:892–900
Monti D, Giannelli R, Chetoni P, Burgalassi S (2001) Comparison of the effect of ultrasound and of chemical enhancers on transdermal permeation of caffeine and morphine through hairless mouse skin in vitro. Int J Pharm 229:131–137
Motlekar NA, Youan B-B (2006) The quest of non-invasive delivery of bioactive macromolecules: a focus on heparins. J Control Release 113:91–101
Murthy SN, Zhao Y-L, Sen A, Hui SW (2004a) Cyclodextrin enhanced transdermal delivery of piroxicam and carboxyfluorescein by electroporation. J Control Release 99:393–402
Murthy SN, Sen A, Hui SW (2004b) Surfactant-enhanced transdermal delivery by electroporation. J Control Release 98:307–315
Murthy SN, Zhao Y-L, Marlan K, Hui SW, Kazim AL, Sen A (2006) Lipid and electroosmosis enhanced transdermal delivery of insulin by electroporation. J Pharm Sci 95(9):2041–2050
Naik A, Kalia YN, Guy RH (2000) Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Technolo Today 3:318–326
Nava-Arzaluz MG, Calderón-Lojero I, Quintanar-Guerrero D, Villalobos-García R, Ganem-Quintanar A (2012) Microneedles as transdermal delivery systems: combination with other enhancing strategies. Curr Drug Deliv 9:57–73
Ogura M, Paliwal S, Mitragotri S (2008) Low-frequency sonophoresis: current status and future prospects. Adv Drug Deliv Rev 60:1218–1223
Pamornpathomkul B, Duangjit S, Laohapatarapant S, Rojanarata T, Opanasopit P, Ngawhirunpat T (2015) Transdermal delivery of fluorescein isothiocyanate-dextrans using the combination of microneedles and low-frequency sonophoresis. Asian J Pharm Sci 10:415–424
Park D, Park H, Seo J, Lee S (2014) Sonophoresis in transdermal drug deliverys. Ultrasonics 54:56–65
Patel D, Kumar P, Thakkar HP (2015) Lopinavir metered-dose transdermal spray through microporated skin: permeation enhancement to achieve therapeutic needs. J Drug Deliv Sci Technol 29:173–180
Pliquett U (1999) Mechanistic studies of molecular transdermal transport due to skin electroporation. Adv Drug Deliv Rev 35(1):41–60
Polat BE, Blankschtein D, Langer R (2010) Low-frequency sonophoresis: application to the transdermal delivery of macromolecules and hydrophilic drugs. Expert Opin Drug Deliv 7:1415–1432
Polat BE, Figueroa PL, Blankschtein D, Langer R (2011a) Transport pathways and enhancement mechanisms within localized and non-localized transport regions in skin treated with low-frequency sonophoresis and sodium lauryl sulfate. J Pharm Sci 100:512–529
Polat BE, Hart D, Langer R, Blankschtein D (2011b) Ultrasound-mediated transdermal drug delivery: mechanisms, scope and emerging trends. J Control Release 152:330–348
Polat BE, Seto JE, Blankschtein D, Langer R (2011c) Application of the aqueous porous pathway model to quantify the effect of sodium lauryl sulfate on ultrasound-induced skin structural perturbation. J Pharm Sci 100:1387–1397
Polat BE, Deen WM, Langer R, Blankschtein D (2012) A physical mechanism to explain the delivery of chemical penetration enhancers into skin during transdermal sonophoresis – Insight into the observed synergism. J Control Release 158:250–260
Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26(11):1261–1268
Qiu Y, Gao Y, Hu K, Li F (2008) Enhancement of skin permeation of docetaxel: a novel approach combining microneedle and elastic liposomes. J Control Release 129:144–150
Sen A, Zhao Y, Hui SW (2002a) Saturated anionic phospholipids enhance transdermal transport by electroporation. Biophys J 83(4):2064–2073
Sen A, Zhao Y, Zhang L, Hui SK (2002b) Enhanced transdermal transport by electroporation using anionic lipids. J Control Release 82:390–405
Sen A, Daly ME, Hui SW (2002c) Transdermal insulin delivery using lipid enhanced electroporation. Biochim Biophys Acta 1564:5–8
Seto JE, Polat BE, Lopez RFV, Blankschtein D, Langer R (2010) Effects of ultrasound and sodium lauryl sulfate on the transdermal delivery of hydrophilic permeants: comparative in vitro studies with full-thickness and split-thickness pig and human skin. J Control Release 145:26–32
Shipton EA (2012) Advances in delivery systems and routes for local anaesthetics. Trends Anaesth Crit Care 2:228–233
Tezel A, Sanders A, Tuchscherer J, Mitragotri S (2002) Synergistic effect of low-frequency ultrasound and surfactants on skin permeability. J Pharm Sci 91:91–100
Thomas BJ, Finnin BC (2004) The transdermal revolution. Drug Discov Today 9:697–703
Tiwari S, Pai R, Udupa N (2004) Influence of ultrasound on the percutaneous absorption of ketorolac tromethamine in vitro across rat skin. Drug Deliv 11:47–51
Tokudome Y, Sugibayashi K (2003) The synergic effects of various electrolytes and electroporation on the in vitro skin permeation of calcein. J Control Release 92(1–2):93–101
Tokudome Y, Sugibayashi K (2004) Mechanism of the synergic effects of calcium chloride and electroporation on the in vitro enhanced skin permeation of drugs. J Control Release 95(2):267–274
Ueda H, Ogihara M, Sugibayashi K, Morimoto Y (1996) Change in the electrochemical properties of skin and the lipid packing in stratum corneum by ultrasonic irradiation. Int J Pharm 137:217–224
Vanbever R, Préat V (2000) Transdermal drug delivery by skin electroporation in the Rat. In: Jaroszeski MJ, Heller R, Gilbert R (eds) Electrochemotherapy, electrogenetherapy, and transdermal drug delivery. Electrically mediated delivery of molecules to cells. Humana Press, Totowa, pp 457–471
Vanbever R, Prausnitz MR, Préat V (1997) Macromolecules as novel transdermal transport enhancers for skin electroporation. Pharm Res 14(5):638–644
Vitorino C, Almeida A, Sousa J, Lamarche I, Gobin P, Marchand S, Couet W, Olivier JC, Pais A (2014) Passive and active strategies for transdermal delivery using co-encapsulating nanostructured lipid carriers: in vitro vs. in vivo studies. Eur J Pharm Biopharm 86:133–144
Watanabe S, Takagi S, Ga K, Yamamoto K, Aoyagi T (2009) Enhanced transdermal drug penetration by the simultaneous application of iontophoresis and sonophoresis. J Drug Del Sci Tech 19:185–189
Weaver JC, Chizmadzhev YA (1996) Theory of electroporation: a review. Bioelectrochem Bioenerg 41:135–160
Weaver JC, Vanbever R, Vaughan TE, Prausnitz MR (1997) Heparin alters transdermal transport associated with electroporation. Biochem Biophys Res Commun 234(3):637–640
Weaver JC, Vaughan TE, Chizmadzhev Y (1999) Theory of electrical creation of aqueous pathways across skin transport barriers. Adv Drug Deliv Rev 35(1):21–39
Wong TW (2014) Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery. J Control Release 193:257–269
Wong T-W, Zhao Y-L, Sen A, Hui SW (2005) Pilot study of topical delivery of methotrexate by electroporation. Br J Dermatol 152(3):524–530
Yang Y, Kalluri H, Banga AK (2011) Effects of chemical and physical enhancement techniques on transdermal delivery of cyanocobalamin (Vitamin B12). Pharmaceutics 3:474–484
Zewert TE, Pliquett UF, Vanbever R, Langer R, Weaver JC (1999) Creation of transdermal pathways for macromolecule transport by skin electroporation and a low toxicity, pathway-enlarging molecule. Bioelectrochem Bioenerg 49:11–20
Zorec B, Jelenc J, Miklavcic D, Pavselj N (2016) Electroporation-enhanced transdermal delivery of patent blue using green skin pore device. IFMBE Proceedings 57:1030–1033
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Piñón-Segundo, E., Nava-Arzaluz, M.G., Ganem-Rondero, A. (2017). Effect of the Use of Chemical Enhancers Combined with Sonophoresis, Electroporation, or Microneedles on Transdermal Drug Delivery. In: Dragicevic, N., I. Maibach, H. (eds) Percutaneous Penetration Enhancers Physical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53273-7_26
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