Journal of the Society of Cosmetic Scientists of Korea (대한화장품학회지)

Society of Cosmetic Scientists of Korea (대한화장품학회)
권호 표지

Enhanced Transdermal Delivery of Drug Compounds Using Scalable and Deformable Ethosomes

에토좀 입자크기와 멤브레인 특성 조절을 통한 약물의 경피흡수능 향상

  • 안은정 (아모레 퍼시픽 기술연구원) ;
  • 심종원 (아모레 퍼시픽 기술연구원) ;
  • 최장원 (아모레 퍼시픽 기술연구원) ;
  • 김진웅 (아모레 퍼시픽 기술연구원) ;
  • 박원석 (아모레 퍼시픽 기술연구원) ;
  • 김한곤 (아모레 퍼시픽 기술연구원) ;
  • 박기동 (아주대학교 분자과학기술학과) ;
  • 한성식 (고려대학교 생명과학대학)
  • Received : 2010.06.15
  • Accepted : 2010.06.22
  • Published : 2010.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study introduces a flexible approach to enhance skin permeation by using ethosomes with deformable lipid membranes as well as controllable sizes. To demonstrate this, a set of ethosomes encapsulating an anti-hair loss ingredient, Triaminodil$^{TM}$, as a model drug, were fabricated with varying their size, which was achieved by solely applying the different level of mechanical energy, while maintaining their chemical composition. After characterization of the ethosomes with dynamic light scattering, transmission electron microscopy, and deformability measurements, it was found that their membrane deformability depended on the particle size. Moreover, studies on in vitro skin permeation and murine anagen induction allowed us to figure out that the membrane deformability of ethosomes essentially affects delivery efficiency of Triaminodil$^{TM}$ through the skin. It was noticeable in our study that there existed an optimum particle size that can not only maximize the delivery of the drug through the skin, but also increase its actual dermatological activity. These findings offer a useful basis for understanding how ethosomes should be designed to improve delivery efficiency of encapsulated drugs therein in the aspects of changing their length scales and membrane properties.

본 연구에서는 입자 크기 뿐만 아니라 베지클 멤브레인의 변형도를 조절할 수 있는 에토좀을 통해 약물의 경피흡수능을 향상시킬 수 있는 새로운 접근을 소개한다. 이를 위해 신규 육모효능성분인 Triaminodil을 포집한 에토좀을 제조하였고 입자 제조 후 추가적인 에너지를 가함으로써 입자의 크기를 조절하였다. 광산란법, 투과전자현미경, 멤브레인 변형도 측정 등을 통해 입자의 변형도가 입자 크기에 의존하는 것을 확인하였다. 또한 in vitro 피부흡수시험과 전임상 성장기 유도평가를 통해 베지클 멤브레인의 변형도가 Triaminodil의 피부 전달효능에 크게 영향을 미치는 것을 확인하였다. 이러한 결과로부터 담지 된 약물의 전달효능을 극대화 시킬 수 있는 최적 크기의 전달체 영역이 존재함을 확인하였고 이는 입자의 크기와 멤브레인 특성에 큰 영향을 받기 때문에 전달체를 설계하는데 있어 이 두 가지 요인을 고려해야 한다.

Keywords

References

  1. A. S. Michaels, S. K. Chandrasekaran, and J. E. Shaw, AlChE J., 21, 985 (1975). https://doi.org/10.1002/aic.690210522
  2. M. R. Prausnitz, S. Mitragotri, and R. Langer, Nat. Rev. Drug Discov., 2, 115 (2004).
  3. A. G. Doukas and N. Kollias, Adv. Drug Deliv. Rev., 56, 559 (2004). https://doi.org/10.1016/j.addr.2003.10.031
  4. A. C. Williams and B. W. Barry, Adv. Drug Deliv. Rev., 56, 603 (2004). https://doi.org/10.1016/j.addr.2003.10.025
  5. H. A. E. Benson, Curr. Drug Delivery, 2, 23 (2005). https://doi.org/10.2174/1567201052772915
  6. M. Mezei and V. Gulasekharam, Life Sci., 26, 1473 (1980). https://doi.org/10.1016/0024-3205(80)90268-4
  7. M. M. A. Elsayed, O. Y. Abdallah, V. F. Naggar, and N. M. Khalafallah, Int. J. Pharm., 332, 1 (2007). https://doi.org/10.1016/j.ijpharm.2006.12.005
  8. M. Foldvari, A. Gesztes, and M. Mezei, J. Microencapsul., 7, 479 (1990). https://doi.org/10.3109/02652049009040470
  9. R. Natsuki, Y. Morita, S. Osawa, and Y. Takeda, Biol. Pharm. Bull., 19, 758 (1996). https://doi.org/10.1248/bpb.19.758
  10. D. D. Verma, S. Verma, G. Blume, and A. Fahr, Int. J. Pharm., 258, 141 (2003). https://doi.org/10.1016/S0378-5173(03)00183-2
  11. J. du Plessis, C. Ramachandran, N. Weiner, and D. G. Mller, Int. J. Pharm., 103, 277 (1994). https://doi.org/10.1016/0378-5173(94)90178-3
  12. M. entjurc, K. Vrhovnik, and J. Kristl, J Control. Rel., 59, 87 (1999). https://doi.org/10.1016/S0168-3659(98)00181-3
  13. P. L. Honeywell-Nguyen and J. A. Bouwstra, Drug Discovery Today : Technologies, 2, 67 (2005). https://doi.org/10.1016/j.ddtec.2005.05.003
  14. M. Kirjavainen, A. Urtti, I. J狎skelinen, T. M. Suhonen, P. Paronen, R. Valjakka-Koskela, J. Kiesvaara, and J. Mnkknen, Biochim. Biophys. Acta, 1304, 179 (1996). https://doi.org/10.1016/S0005-2760(96)00126-9
  15. G. M. M. El Maghraby, A. C. Williams, and B. W. Barry, Int. J. Pharm., 276, 143 (2004). https://doi.org/10.1016/j.ijpharm.2004.02.024
  16. M. Trotta, E. Peira, M. E. Carlotti, and M. Gallarate, Int. J. Pharm., 270, 119 (2004). https://doi.org/10.1016/j.ijpharm.2003.10.006
  17. M. Kirjavainen, A. Urtti, R. Valjakka-Koskela, J. Kiesvaara, and J. Mnkknen, Eur. J. Pharm. Sci., 7, 279 (1999). https://doi.org/10.1016/S0928-0987(98)00037-2
  18. N. Dragicevic-Curic, D. Scheglmann, V. Albrecht, and A. Fahr, Colloid Surf. B : Biointerf., 74, 114 (2009). https://doi.org/10.1016/j.colsurfb.2009.07.005
  19. E. Touitou, N. Dayan, L. Bergelson, B. Godin, and M. Eliaz, J. Control. Rel., 65, 403 (2000). https://doi.org/10.1016/S0168-3659(99)00222-9
  20. J. M. Lpez-Pinto, M. L. Gonzlez-Rodrguez, and A. M. Rabasco, Int. J. Pharm., 298, 1 (2005). https://doi.org/10.1016/j.ijpharm.2005.02.021
  21. D. Paolino, G. Lucania, D. Mardente, F. Alhaique, and M. Fresta, J. Control. Rel., 106, 99 (2005). https://doi.org/10.1016/j.jconrel.2005.04.007
  22. S. Jain, A. K. Tiwary, B. Sapra, and N. K. Jain, AAPS PharmSciTech, 8, E1 (2007).
  23. Y. P. Fang, Y. H. Tsai, P. C. Wu, and Y. B. Huang, Int. J. Pharm., 356, 144 (2008). https://doi.org/10.1016/j.ijpharm.2008.01.020
  24. W. S. Park, N. H. Park, J. S. Hwang, and I. S. Jang, The 5th International Congress of Hair Research, Vancouver, Canada (2007).
  25. W. S. Park, N. H. Park, J. S. Han, S. Y. Baek, J. S. Hwang, and I. S. Jang, WO patent 046577 (2007).
  26. G. C. Davies, M. J. Thornton, T. J. Jenner, Y. J. Chen, J. B. Hansen, R. D. Carr, and V. A. Randall, J. Invest. Dermatol., 124, 686 (2005). https://doi.org/10.1111/j.0022-202X.2005.23643.x
  27. B. A. I. van den Bergh, P. W. Wertz, H. E. Junginger, and J. A. Bouwstra, Int. J. Pharm., 217, 13 (2001). https://doi.org/10.1016/S0378-5173(01)00576-2
  28. K. Dimitrievski, Langmuir, 26, 3008 (2010). https://doi.org/10.1021/la904743d
  29. E. Reimhult, F. H拓k, and B. Kasemo, J. Chem. Phys., 117, 7401 (2002). https://doi.org/10.1063/1.1515320
  30. M. Antonietti and S. Frster, Adv. Mater., 15, 1323 (2003). https://doi.org/10.1002/adma.200300010
  31. M. M. A. E. Claessens, B. F. van Oort, F. A. M. Leermakers, F. A. Hoekstra, and M. A. Cohen Stuart, Biophys. J., 87, 3882 (2004). https://doi.org/10.1529/biophysj.103.036772
  32. W. Rawicz, K. C. Olbrich, T. Mclntosh, D. Needham, and E. Evans, Biophys. J., 79, 328 (2000). https://doi.org/10.1016/S0006-3495(00)76295-3