volume | PIER Journals

Abstract

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.

1. Barry, B. W., "Novel mechanisms and devices to enable successful transdermal drug delivery," Eur. J. Pharm. Sci., Vol. 14, 101-114, 2001.
doi:10.1016/S0928-0987(01)00167-1 Google Scholar

2. Ranade, V. V., "Drug delivery systems. 6. Transdermal drug delivery," J. Clin. Pharmacol., Vol. 31, 401-418, 1991.
doi:10.1002/j.1552-4604.1991.tb01895.x Google Scholar

3. Arora, A., M. R. Prausnitz, and S. Mitragotri, "Micro-scale devices for transdermal drug delivery," Int. J. Pharm., Vol. 364, 227-236, 2008.
doi:10.1016/j.ijpharm.2008.08.032 Google Scholar

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.
doi:10.3109/10837450.2010.522584 Google Scholar

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.
doi:10.1016/j.cherd.2008.06.002 Google Scholar

6. Gill, H. S. and M. R. Prausnitz, "Coated microneedles for transdermal delivery," J. Controlled Release, Vol. 117, 227-237, 2007.
doi:10.1016/j.jconrel.2006.10.017 Google Scholar

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.
doi:10.1016/j.ijpharm.2008.10.008 Google Scholar

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.
doi:10.1016/j.mseb.2006.02.008 Google Scholar

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.
doi:10.1016/j.jconrel.2009.03.018 Google Scholar

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.
doi:10.1016/j.ijpharm.2012.02.039 Google Scholar

11. Lavon, I. and J. Kost, "Ultrasound and transdermal drug delivery," Drug Discov. Today, Vol. 9, 670-676, 2004.
doi:10.1016/S1359-6446(04)03170-8 Google Scholar

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.
doi:10.1016/S0168-3659(99)00178-9 Google Scholar

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.
doi:10.1016/j.ultrasmedbio.2011.12.015 Google Scholar

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.
doi:10.1046/j.1523-1747.1998.00415.x Google Scholar

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.
doi:10.1016/j.addr.2003.10.027 Google Scholar

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.
doi:10.1016/S1007-0214(05)70115-2 Google Scholar

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.
doi:10.1016/S1461-5347(00)00295-9 Google Scholar

18. Thomas, B. J. and B. C. Finnin, "The transdermal revolution," Drug Discov. Today, Vol. 9, 697-703, 2004.
doi:10.1016/S1359-6446(04)03180-0 Google Scholar

19. Wong, T. W., "Use of microwave in processing of drug delivery systems," Curr. Drug Deliv., Vol. 5, 77-84, 2008.
doi:10.2174/156720108783954842 Google Scholar

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.
doi:10.1016/j.jfoodeng.2004.04.017 Google Scholar

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.
doi:10.1016/j.surfcoat.2004.07.034 Google Scholar

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.
doi:10.1016/j.surfcoat.2005.01.114 Google Scholar

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.
doi:10.1016/S0360-3016(00)00473-9 Google Scholar

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.
doi:10.1016/S0022-5347(01)67613-4 Google Scholar

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.
doi:10.1016/S0090-4295(98)00471-3 Google Scholar

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.
doi:10.1016/j.eururo.2004.01.019 Google Scholar

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.
doi:10.1093/bmb/ldm020 Google Scholar

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.
doi:10.1016/S0002-9610(05)80013-3 Google Scholar

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.
doi:10.1016/S0029-7844(02)01663-0 Google Scholar

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. Google Scholar

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.
doi:10.1109/TMTT.2004.823596 Google Scholar

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.
doi:10.1016/j.jpba.2006.08.014 Google Scholar

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.
doi:10.1016/j.ijpharm.2007.05.034 Google Scholar

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.
doi:10.1016/j.carbpol.2005.07.029 Google Scholar

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.
doi:10.3109/03639041003695063 Google Scholar

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.
doi:10.1016/j.ejpb.2007.09.015 Google Scholar

37. Zakaria, Z. and T. W. Wong, "Chitosan spheroids with microwave modulated drug release," Progress In Electromagnetics Research, Vol. 99, 355-382, 2009.
doi:10.2528/PIER09101001 Google Scholar

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.
doi:10.1016/j.jconrel.2005.03.003 Google Scholar

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.
doi:10.1080/03639040601015513 Google Scholar

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.
doi:10.1016/j.ijpharm.2008.01.047 Google Scholar

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.
doi:10.1016/j.ijpharm.2010.09.008 Google Scholar

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.
doi:10.1007/s11095-012-0852-z Google Scholar

43. Costa, P. and J. M. S. Lobo, "Modeling and comparison of dissolution profiles," Eur. J. Pharm. Sci., Vol. 13, 123-133, 2001.
doi:10.1016/S0928-0987(01)00095-1 Google Scholar

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. Google Scholar

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.
doi:10.1016/j.ijpharm.2005.10.008 Google Scholar

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.
doi:10.1016/j.bbamem.2007.05.028 Google Scholar

47. Williams, A. C. and B. W. Barry, "Penetration enhancers," Adv. Drug Deliv. Rev., Vol. 56, 603-618, 2004.
doi:10.1016/j.addr.2003.10.025 Google Scholar

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.
doi:10.1016/j.jconrel.2009.04.023 Google Scholar

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.
doi:10.1016/S0009-3084(97)00105-9 Google Scholar

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.
doi:10.1016/j.colsurfa.2009.09.025 Google Scholar

Dr. Anuar Nor Khaizan

Prof. Tin Wui Wong