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Physicochemical Modulation of Skin Barrier by Microwave for Transdermal Drug Delivery

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ABSTRACT

Purpose

To investigate mechanism of microwave enhancing drug permeation transdermally through its action on skin.

Methods

Hydrophilic pectin-sulphanilamide films, with or without oleic acid (OA), were subjected to drug release and skin permeation studies. The skins were untreated or microwave-treated, and characterized by infrared spectroscopy, Raman spectroscopy, thermal, electron microscopy and histology techniques.

Results

Skin treatment by microwave at 2450 MHz for 5 min promoted drug permeation from OA-free film without incurring skin damage. Skin treatment by microwave followed by film loaded with drug and OA resulted in permeation of all drug molecules that were released from film. Microwave exerted spacing of lipid architecture of stratum corneum into structureless domains which was unattainable by OA. It allowed OA to permeate stratum corneum and accumulate in dermis at a greater ease, and synergistically inducing lipid/keratin fluidization at hydrophobic C-H and hydrophilic O-H, N-H, C-O, C=O, C-N regimes of skin, and promoting drug permeation.

Conclusion

The microwave technology is evidently feasible for use in promotion of drug permeation across the skin barrier. It represents a new approach in transdermal drug delivery.

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REFERENCES

  1. Wong TW. Use of microwave in processing of drug delivery systems. Curr Drug Deliv. 2008;5:77–84.

    Article  PubMed  CAS  Google Scholar 

  2. Nakamura H, Matsuzaki I, Hatta K, Nobukuni Y, Kambayashi Y, Ogino K. Nonthermal effects of mobile-phone frequency microwaves on uteroplacental functions in pregnant rats. Reprod Toxicol. 2003;17:321–6.

    Article  PubMed  CAS  Google Scholar 

  3. Colombo R, Lev A, Da Pozzo LF, Freschi M, Gallus G, Rigatti P. A new approach using local combined microwave hyperthermia and chemotherapy in superficial transitional bladder carcinoma treatment. J Urol. 1995;153:959–63.

    Article  PubMed  CAS  Google Scholar 

  4. Van der Heijden AG, Kiemeney LA, Gofrit ON, Nativ O, Sidi A, Leib Z, Colombo R, Naspro R, Pavone M, Baniel J, Hasner F, Witjes JA. Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder. Eur Urol. 2004;46:65–72.

    Article  PubMed  Google Scholar 

  5. Anscher MS, Lee C, Hurwitz H, Tyler D, Prosnitz LR, Jowell P, Rosner G, Samulski T, Dewhirst MW. A pilot study of preoperative continuous infusion of 5-fluorouracil, external microwave hyperthermia, and external beam radiotherapy for treatment of locally advanced, unresectable, or recurrent rectal cancer. Int J Radiat Oncol Biol Phys. 2000;47:719–24.

    Article  PubMed  CAS  Google Scholar 

  6. Djavan B, Larson TR, Blute ML, Marberger M. Transurethral microwave thermotherapy: what role should it play versus medical management in the treatment of benign prostatic hyperplasia. Urol. 1998;52:935–47.

    Article  PubMed  CAS  Google Scholar 

  7. Giombini A, Giovannini V, Di Cesare A, Pacetti P, Ichinoseki-Sekine N, Shiraishi M, Naito H, Maffulli N. Hyperthermia induced by microwave diathermy in the management of muscle and tendon injuries. Br Med Bull. 2007;83:379–96.

    Article  PubMed  CAS  Google Scholar 

  8. Korpan NN, Saradeth T. Clinical effects of continuous microwave for postoperative septic wound treatment: a double-blind controlled trial. Am J Surg. 1995;170:271–6.

    Article  PubMed  CAS  Google Scholar 

  9. Nor Khaizan A, Wong TW, Mohd Nasir T. Microwave modified non-crosslinked pectin films with modulated drug release. Pharm Dev Tech. 2012;17:110–7.

    Google Scholar 

  10. Meyer DE, Shin BC, Kong GA, Dewhirst MW, Chilkoti A. Drug targeting using thermally responsive polymers and local hyperthermia. J Control Release. 2001;74:213–24.

    Article  PubMed  CAS  Google Scholar 

  11. Moriyama E, Salcman M, Broadwell RD. Blood–brain barrier alteration after microwave-induced hyperthermia is purely a thermal effect: I: temperature and power measurements. Surg Neurol. 1991;35:1771–82.

    Article  Google Scholar 

  12. Fadilah R, Pinkas J, Weinberger A, Lev A. Heating rabbit joint by microwave applicator. Arch Phys Med Rehabil. 1987;68:710–2.

    PubMed  CAS  Google Scholar 

  13. Yang WJ, Wang JH. Shortwave and microwave diathermy for deep-tissue heating. Med Biol Eng Comput. 1979;17:518–24.

    Article  PubMed  CAS  Google Scholar 

  14. Ruddy SB, Hadzija BW. The role of stratum corneum in electrically facilitated transdermal drug delivery. I. Influence of hydration, tape-stripping and delipidization on the DC electrical properties of skin. J Control Release. 1995;37:225–38.

    Article  CAS  Google Scholar 

  15. Gill HS, Andrews SN, Sakthivel SK, Fedanov A, Williams IR, Garber DA, Priddy FH, Yellin S, Feinberg MB, Staprans SI, Prausnitz MR. Selective removal of stratum corneum by microdermabrasion to increase skin permeability. Eur J Pharm Sci. 2009;38:95–103.

    Article  PubMed  CAS  Google Scholar 

  16. Babu RJ, Pandit JK. Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems. Int J Pharm. 2005;288:325–34.

    Article  PubMed  CAS  Google Scholar 

  17. Lee PJ, Ahmad N, Langer R, Mitragotri S, Shastri VP. Evaluation of chemical enhancers in the transdermal delivery of lidocaine. Int J Pharm. 2006;308:33–9.

    Article  PubMed  CAS  Google Scholar 

  18. Lavon I, Kost J. Ultrasound and transdermal drug delivery. Drug Discov Today. 2004;9:670–6.

    Article  PubMed  CAS  Google Scholar 

  19. Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Tech Today. 2000;3:318–26.

    Article  CAS  Google Scholar 

  20. 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;88:85–94.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang HY, Yeo SH. Design and fabrication of a sonophoresis device with a flat flextensional transducer for transdermal drug delivery. Sensor Actuat A-Phys. 2004;115:133–9.

    Article  Google Scholar 

  22. Henchoz Y, Abla N, Veuthey JL, Carrupt PA. A fast screening strategy for characterizing peptide delivery by transdermal iontophoresis. J Control Release. 2009;137:123–9.

    Article  PubMed  CAS  Google Scholar 

  23. Wang Y, Thakur R, Fan Q, Michniak B. Transdermal iontophoresis: combination strategies to improve transdermal iontophoretic drug delivery. Eur J Pharm Biopharm. 2005;60:179–91.

    Article  PubMed  CAS  Google Scholar 

  24. Denet AR, Vanbever R, Préat V. Skin electroporation for transdermal and topical delivery. Adv Drug Del Rev. 2004;56:659–74.

    Article  CAS  Google Scholar 

  25. Sung KC, Fang JY, Wang JJ, Hu OYP. Transdermal delivery of nalbuphine and its prodrugs by electroporation. Eur J Pharm Sci. 2003;18:63–70.

    Article  PubMed  CAS  Google Scholar 

  26. Davidson A, Al-Qallaf B, Das DB. Transdermal drug delivery by coated microneedles: geometry effects on effective skin thickness and drug permeability. Chem Eng Res Des. 2008;86:1196–206.

    Article  CAS  Google Scholar 

  27. Teo AL, Shearwood C, Ng KC, Lu J, Moochhala S. Transdermal microneedles for drug delivery applications. Mater Sci Eng B. 2006;132:151–4.

    Article  CAS  Google Scholar 

  28. Lee S, McAuliffe DJ, Flotte TJ, Kollias N, Doukas AG. Photomechanical transcutaneous delivery of macromolecules. J Invest Dermatol. 1998;111:925–9.

    Article  PubMed  CAS  Google Scholar 

  29. Singh H, Grewal A, Kaur B. Needle free lidocaine delivery system. J Anaesth Clin Pharmaco. 2009;25:193–8.

    CAS  Google Scholar 

  30. Moghimi HR, Alinaghi A, Erfan M. Investigating the potential of non-thermal microwave as a novel skin penetration enhancement method. Int J Pharm. 2010;401:47–50.

    Article  PubMed  CAS  Google Scholar 

  31. Costa P, Manuel J, Lobo S. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–33.

    Article  PubMed  CAS  Google Scholar 

  32. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56:603–18.

    Article  PubMed  CAS  Google Scholar 

  33. Durney CH, Massoudi H, lskander MH. In Radiofrequency Radiation Dosimetry Handbook, 4th edn. USAF School of Aerospace Medicine, Aerospace Medical Division (AFSC) Brooks Air Force Base, USA, 1986.

  34. Engin K, Tupchong L, Waterman FM, McFarlane JD, Hoh LL, Leeper DB. Predictive factors for skin reactions in patients treated with thermoradiotherapy. Int J Hyperther. 1995;11:357–64.

    Article  CAS  Google Scholar 

  35. Silva CL, Topgaard D, Kocherbitov V, Sousa JJS, Pais AACC, Sparr E. Stratum corneum hydration: phase transformations and mobility in stratum corneum, extracted lipids and isolated corneocytes. Biochim Biophys Acta. 2007;1768:2647–59.

    Article  PubMed  CAS  Google Scholar 

  36. Guillard EC, Tfayli A, Laugel C, Baillet-Guffroy A. Molecular interactions of penetration enhancers within ceramides organization: a FTIR approach. Eur J Pharm Sci. 2009;38:192–9.

    Article  Google Scholar 

  37. Rowat AC, Kitson N, Thewalt JL. Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR. Int J Pharm. 2006;307:225–31.

    Article  PubMed  CAS  Google Scholar 

  38. Mélot M, Pudney PDA, Williamson A-M, Caspers PJ, Van Der Pol A, Puppels GJ. Studying the effectiveness of penetration enhancers to deliver retinol through the stratum corneum by in vivo confocal Raman spectroscopy. J Control Release. 2009;138:32–9.

    Article  PubMed  Google Scholar 

  39. Wartewig S, Neubert R, Rettig W, Hesse K. Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. IV. Mixtures of ceramides and oleic acid. Chem Phys Lipids. 1998;91:145–52.

    Article  CAS  Google Scholar 

  40. Zbytovská J, Vávrová K, Kiselev MA, Lessieur P, Wartewig S, Neubert RHH. The effects of transdermal permeation enhancers on thermotropic phase behaviour of a stratum corneum lipid model. Colloid Surface A. 2009;351:30–7.

    Article  Google Scholar 

  41. Lawson EE, Anigbogu ANC, Williams AC, Barry BW, Edwards HGM. Thermally induced molecular disorder in human stratum corneum lipids compared with a model phospholipid system: FT-Raman spectroscopy. Spectrochim Acta A. 1998;54:543–58.

    Article  Google Scholar 

  42. Boncheva M, Damien F, Normand V. Molecular organization of the lipid matrix in intact stratum corneum using ATR-FTIR spectroscopy. Biochim Biophys Acta. 2008;1778:1344–55.

    Article  PubMed  CAS  Google Scholar 

  43. Joshi A, Raje J. Sonicated transdermal drug transport. J Control Release. 2002;83:13–22.

    Article  PubMed  CAS  Google Scholar 

  44. Nanda A, Nanda S, Khan Ghilzai NM. Current developments using emerging transdermal technologies in physical enhancement methods. Curr Drug Deliv. 2006;3:233–42.

    Article  PubMed  CAS  Google Scholar 

  45. Tiwary AK, Sapra B, Jain S. Innovations in transdermal drug delivery: formulations and techniques. Recent Pat Drug Deliv Formulation. 2007;1:23–36.

    Article  CAS  Google Scholar 

  46. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14:101–14.

    Article  PubMed  CAS  Google Scholar 

  47. Banga AK, Bose S, Ghosh TK. Iontophoresis and electroporation: comparisons and contrasts. Int J Pharm. 1999;179:1–19.

    Article  PubMed  CAS  Google Scholar 

  48. Jadoul A, Bouwstra J, Préat V. Effects of iontophoresis and electroporation on the stratum corneum: review of the biophysical studies. Adv Drug Deliv Rev. 1999;35:89–105.

    Article  PubMed  CAS  Google Scholar 

  49. Panchagnula R, Pillai O, Nair VB, Ramarao P. Transdermal iontophoresis revisited. Curr Opin Chem Biol. 2000;4:468–73.

    Article  PubMed  CAS  Google Scholar 

  50. Prausnitz MR, Lee CS, Liu CH, Pang JC, Singh T-P, Langer R, Weaver JC. Transdermal transport efficiency during skin electroporation and iontophoresis. J Control Release. 1996;38:205–17.

    Article  CAS  Google Scholar 

  51. Cázares-Delgadillo J, Balaguer-Fernandez C, Calatayud-Pascual A, Ganem-Rondero A, Quintanar-Guerrero D, Lopez Castellano AC, Merino V, Kalia YN. Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability and transport kinetics. Eur J Pharm Biopharm. 2010;75:173–8.

    Article  PubMed  Google Scholar 

  52. Taveira SF, Nomizo A, Lopez RFV. Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicity. J Control Release. 2009;134:35–40.

    Article  PubMed  CAS  Google Scholar 

  53. Calatayud-Pascual MA, Balaguer-Fernandez C, Serna-Jimenez CE, Del Rio-Sancho S, Femenia-Font A, Merino V, Lopez Castellano A. Effect of iontophoresis on in vitro transdermal absorption of almotriptan. Int J Pharm. 2011;416:189–94.

    Article  PubMed  CAS  Google Scholar 

  54. Oshizaka T, Todo H, Sugibayashi K. Effect of direction (Epidermis-to-dermis and dermis-to-epidermis) on the permeation of several chemical compounds through full-thickness skin and stripped skin. Pharm Res. doi:10.1007/s11095-012-0777-6

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors wish to express heart-felt thanks to Ministry of Science, Technology and Innovation, Malaysia, and Ministry of Higher Education, Malaysia (0141903) for financial and facility support given throughout the research study.

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Authors and Affiliations

  1. Non-Destructive Biomedical and Pharmaceutical Research Centre, Universiti Teknologi MARA, 42300, Puncak Alam, Selangor, Malaysia

    Tin Wui Wong & Anuar Nor Khaizan

  2. Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, 42300, Puncak Alam, Selangor, Malaysia

    Tin Wui Wong & Anuar Nor Khaizan

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  1. Tin Wui Wong
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Correspondence to Tin Wui Wong.

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Wong, T.W., Nor Khaizan, A. Physicochemical Modulation of Skin Barrier by Microwave for Transdermal Drug Delivery. Pharm Res 30, 90–103 (2013). https://doi.org/10.1007/s11095-012-0852-z

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  • DOI: https://doi.org/10.1007/s11095-012-0852-z

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