This study investigated transdermal drug delivery mechanisms of pectin and pectin-oleic acid (OA) gels and their effects on skin barrier treated by microwave. Hydrophilic pectin-sulphanilamide gels, with or without OA penetration enhancer, 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. Unlike solid film, skin treatment by microwave at 2450 MHz demoted drug permeation especially from OA-rich pectin gel. The pectin-skin binding was facilitated by gel with freely soluble pectin molecules instead of solid film with entangled chains. It was promoted when microwave fluidized stratum corneum into structureless domains, or OA extracted endogenous lipid fraction and formed separate phases within intercellular lipid lamellae. This led to a remarkable decrease in transdermal drug permeation. Microwave-enhanced transdermal delivery must not be implemented with pectin gel. In skin treated by microwave, the penetration enhancer in gel can act as a permeation retardant.
2. Ranade, V. V., "Drug delivery systems. 6. Transdermal drug delivery," J. Clin. Pharmacol., Vol. 31, 401-418, 1991.
3. Arora, A., M. R. Prausnitz, and S. Mitragotri, "Micro-scale devices for transdermal drug delivery," Int. J. Pharm., Vol. 364, 227-236, 2008.
4. Nor Khaizan, A., T. W. Wong, and T. Mohd Nasir, "Microwave modified non-crosslinked pectin films with modulated drug release," Pharm. Dev. Technol., Vol. 17, 110-117, 2012.
5. Davidson, A., B. Al-Qallaf, and D. B. Das, "Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability," Chem. Eng. Res. Des., Vol. 86, 1196-1206, 2008.
6. Gill, H. S. and M. R. Prausnitz, "Coated microneedles for transdermal delivery," J. Controlled Release, Vol. 117, 227-237, 2007.
7. Li, G., A. Badkar, S. Nema, C. S. Kolli, and A. K. Banga, "In vitro transdermal delivery of therapeutic antibodies using maltose microneedles," Int. J. Pharm., Vol. 368, 109-115, 2009.
8. Teo, A. L., C. Shearwood, K. C. Ng, J. Lu, and S. Moochhala, "Transdermal microneedles for drug delivery applications," Mater. Sci. Eng. B, Vol. 132, 151-154, 2006.
9. Henchoz, Y., N. Abla, J. L. Veuthey, and P. A. Carrupt, "A fast screening strategy for characterizing peptide delivery by transdermal iontophoresis," J. Controlled Release, Vol. 137, 123-129, 2009.
10. Che, X., L.-H. Wang, Y. Yuan, Y.-N. Gao, Q.-F. Wang, Y. Yang, and S.-M. Li, "A novel method to enhance the efficiency of drug transdermal iontophoresis delivery by using complexes of drug and ion-exchange fibers," Int. J. Pharm., Vol. 428, 68-75, 2012.
11. Lavon, I. and J. Kost, "Ultrasound and transdermal drug delivery," Drug Discov. Today, Vol. 9, 670-676, 2004.
12. Mitragotri, S., J. Farrell, H. Tang, T. Terahara, J. Kost, and R. Langer, "Determination of threshold energy dose for ultrasound-induced transdermal drug transport," J. Controlled Release, Vol. 63, 41-52, 2000.
13. Park, D., H. Ryu, H. S. Kim, Y.-S. Kim, K.-S. Choi, H. Park, and J. Seo, "Sonophoresis using ultrasound contrast agents for transdermal drug delivery: An in vivo experimental study," Ultrasound Med. Biol., Vol. 38, 642-650, 2012.
14. Lee, S., D. J. McAuliffe, T. J. Flotte, N. Kollias, and A. G. Doukas, "Photomechanical transcutaneous delivery of macromolecules," J. Invest. Dermatol., Vol. 111, 925-929, 1998.
15. Denet, A. R., R. Vanbever, and V. Preat, "Skin electroporation for transdermal and topical delivery," Adv. Drug Deliv. Rev., Vol. 56, 659-674, 2004.
16. Zan, J., G. Jiang, Y. Lin, F. Tan, and F. Ding, "Transdermal delivery of piroxicam by surfactant mediated electroporation," Tsinghua Sci. Technol., Vol. 10, 542-547, 2005.
17. Naik, A., Y. N. Kalia, and R. H. Guy, "Transdermal drug delivery: Overcoming the skin's barrier function," Pharm. Sci. Technol. Today, Vol. 3, 318-326, 2000.
18. Thomas, B. J. and B. C. Finnin, "The transdermal revolution," Drug Discov. Today, Vol. 9, 697-703, 2004.
19. Wong, T. W., "Use of microwave in processing of drug delivery systems," Curr. Drug Deliv., Vol. 5, 77-84, 2008.
20. Goksu, E. I., G. Sumnu, and A. Esin, "Effect of microwave on fluidized bed drying of macaroni beads," J. Food Eng., Vol. 66, 463-468, 2005.
21. Lee, K. Y., B. J. Park, D. H. Lee, I.-S. Lee, S. O. Hyun, K.-H. Chung, and J.-C. Park, "Sterilization of Escherichia coli and MRSA using microwave-induced argon plasma at atmospheric pressure," Surface & Coatings Technol., Vol. 193, 35-38, 2005.
22. Schneider, J., K. M. Baumgartner, J. Feichtinger, J. Kruger, P. Muranyi, A. Schulz, M. Walker, J. Wunderlich, and U. Schumacher, "Investigation of the practicability of low-pressure microwave plasmas in the sterilization of food packaging materials at industrial level," Surface & Coatings Technol., Vol. 200, 962-966, 2005.
23. Anscher, M. S., C. Lee, H. Hurwitz, D. Tyler, L. R. Prosnitz, P. Jowell, G. Rosner, T. Samulski, and M. W. Dewhirst, "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., Vol. 47, 719-724, 2000.
24. Colombo, R., A. Lev, L. F. Da Pozzo, M. Freschi, G. Gallus, and P. Rigatti, "A new approach using local combined microwave hyperthermia and chemotherapy in superficial transitional bladder carcinoma treatment," J. Urol., Vol. 153, 959-963, 1995.
25. Djavan, B., T. R. Larson, M. L. Blute, and M. Marberger, "Transurethral microwave thermotherapy: What role should it play versus medical management in the treatment of benign prostatic hyperplasia," J. Urol., Vol. 52, 935-947, 1998.
26. Van der Heijden, A. G., L. A. Kiemeney, O. N. Gofrit, O. Nativ, A. Sidi, Z. Leib, R. Colombo, R. Naspro, M. Pavone, J. Baniel, F. Hasner, and J. A. Witjes, "Preliminary european results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder," Eur. Urol., Vol. 46, 65-72, 2004.
27. Giombini, A., V. Giovannini, A. Di Cesare, P. Pacetti, N. Ichinoseki-Sekine, M. Shiraishi, H. Naito, and N. Maffulli, "Hyperthermia induced by microwave diathermy in the management of muscle and tendon injuries," Br. Med. Bull., Vol. 83, 379-396, 2007.
28. Korpan, N. N. and T. Saradeth, "Clinical effects of continuous microwave for postoperative septic wound treatment: A double-blind controlled trial," Am. J. Surg., Vol. 170, 271-276, 1995.
29. Bain, C., K. G. Cooper, and D. E. Parkin, "Microwave endometrial ablation versus endometrial resection: A randomized controlled trial," Obstet. Gynecol., Vol. 99, 983-987, 2002.
30. Saleh, W. and N. Qaddoumi, "Breast cancer detection using non-invasive near-field microwave nondestructive testing techniques," Proceedings of the Asia-Pacific Conference on Applied Electromagnetics, 109-112, 2003.
31. Massood, T. A. and Y. Wang, "Design and fabrication of scanning near-field microwave probes compatible with atomic force microscopy to image embedded nanostructures," IEEE Trans. on Microwave Theory and Techniques, Vol. 52, 971-979, 2004.
32. Nor Khaizan, A., T. W. Wong, D. K. Ghodgaonkar, and T. Mohd Nasir, "Characterization of hydroxypropylmethylcellu-lose films using microwave non-destructive testing technique," J. Pharm. Biomed. Anal., Vol. 43, 549-557, 2007.
33. Wong, T. W., D. K. Ghodgaonkar, T. Mohd Nasir, and A. Nor Khaizan, "Microwave non-destructive testing technique for characterization of HPMC-PEG 3000 films," Int. J. Pharm., Vol. 343, 122-130, 2007.
34. Nurjaya, S. and T. W. Wong, "Effects of microwave on drug release properties of matrices of pectin," Carbohyd. Polym., Vol. 62, 245-257, 2005.
35. Radman, E. M. and T. W. Wong, "Effects of microwave on drug release responses of spray-dried alginate microspheres," Drug Dev. Ind. Pharm., Vol. 36, 1149-1167, 2010.
36. Wong, T. W. and N. Sumiran, "Drug release property of chitosan-pectinate beads and its changes under the influence of microwave," Eur. J. Pharm. Biopharm., Vol. 69, 176-188, 2008.
37. Zakaria, Z. and T. W. Wong, "Chitosan spheroids with microwave modulated drug release," Progress In Electromagnetics Research, Vol. 99, 355-382, 2009.
38. Wong, T. W., L. W. Chan, S. B. Kho, and P. W. S. Heng, "Aging and microwave effects on alginate/chitosan matrices," J. Controlled Release, Vol. 104, 461-475, 2005.
39. Wong, T. W., A. W. Selasiah, and A. Yolande, "Effects of microwave on drug release property of poly (methyl vinyl ether-co-maleic acid) matrix," Drug Dev. Ind. Pharm., Vol. 33, 737-746, 2007.
40. Wong, T. W., A. W. Selasiah, and A. Yolande, "Drug release responses of zinc ion crosslinked poly (methyl vinyl ether-co-maleic acid) matrix towards microwave," Int. J. Pharm., Vol. 357, 154-163, 2008.
41. Moghimi, H. R., A. Alinaghi, and M. Erfan, "Investigating the potential of non-thermal microwave as a novel skin penetration enhancement method," Int. J. Pharm., Vol. 401, 47-50, 2010.
42. Wong, T. W. and A. Nor Khaizan, "Physicochemical modulation of skin barrier by microwave for transdermal drug delivery," Pharm. Res., Vol. 30, 90-103, 2013.
43. Costa, P. and J. M. S. Lobo, "Modeling and comparison of dissolution profiles," Eur. J. Pharm. Sci., Vol. 13, 123-133, 2001.
44. Srivastava, P. and R. Malviya, "Sources of pectin, extraction and its applications in pharmaceutical industry - An overview," Indian J. Nat. Prod. Resour., Vol. 2, 10-18, 2011.
45. Rowat, A. C., N. Kitson, and J. L. Thewalt, "Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR," Int. J. Pharm., Vol. 307, 225-231, 2006.
46. Silva, C. L., D. Topgaard, V. Kocherbitov, J. J. S. Sousa, A. A. C. C. Pais, and E. Sparr, "Stratum corneum hydration: Phase transformations and mobility in stratum corneum, extracted lipids and isolated corneocytes," Biochim. Biophys. Acta, Vol. 1768, 2647-2659, 2007.
47. Williams, A. C. and B. W. Barry, "Penetration enhancers," Adv. Drug Deliv. Rev., Vol. 56, 603-618, 2004.
48. Melot, M., P. D. A. Pudney, A. M. Williamson, P. J. Caspers, A. van Der Pol, and G. J. Puppels, "Studying the effectiveness of penetration enhancers to deliver retinol through the stratum corneum by in vivo confocal Raman spectroscopy," J. Controlled Release, Vol. 138, 32-39, 2009.
49. Wartewig, S., R. Neubert, W. Rettig, and K. Hesse, "Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. IV. Mixtures of ceramides and oleic acid," Chem. Phys. Lipids, Vol. 91, 145-152, 1998.
50. Zbytovska, J., K. Vavrova, M. A. Kiselev, P. Lessieur, S.Wartewig, and R. H. H. Neubert, "The effects of transdermal permeation enhancers on thermotropic phase behaviour of a stratum corneum lipid model," Colloid Surface A, Vol. 351, 30-37, 2009.