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

Society of Cosmetic Scientists of Korea (대한화장품학회)
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Hyaluronic Acid Enhances the Dermal Delivery of Anti-wrinkle Peptide via Increase of Stratum Corneum Fluidity

히알루론산의 각질 유동성 향상을 통한 주름 개선 펩타이드 피부 흡수 촉진

  • Kim, Yun-Sun (LG Science Park, LG Household & Healthcare Ltd.) ;
  • Kim, Daehyun (LG Science Park, LG Household & Healthcare Ltd.) ;
  • Kim, Yumi (LG Science Park, LG Household & Healthcare Ltd.) ;
  • Park, Sun-Gyoo (LG Science Park, LG Household & Healthcare Ltd.) ;
  • Lee, Cheon-Koo (LG Science Park, LG Household & Healthcare Ltd.) ;
  • Kang, Nae-Gyu (LG Science Park, LG Household & Healthcare Ltd.)
  • 김윤선 ((주) LG생활건강 기술연구원) ;
  • 김대현 ((주) LG생활건강 기술연구원) ;
  • 김유미 ((주) LG생활건강 기술연구원) ;
  • 박선규 ((주) LG생활건강 기술연구원) ;
  • 이천구 ((주) LG생활건강 기술연구원) ;
  • 강내규 ((주) LG생활건강 기술연구원)
  • Received : 2018.10.31
  • Accepted : 2018.12.19
  • Published : 2018.12.30
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Abstract

Acetyl hexapeptide 8 (AH8) is a synthetic peptide for anti-wrinkle cosmetics ingredient. It was developed as a mimetic of botox, patternd after N -terminal end of the protein synatosomal-associated protein 25 (SNAP25), a substrate of botulinum toxin. While AH8 has good efficacy and safety profiles, the permeation through the skin is poor. Therefore, we tried to enhance the transdermal delivery of AH8 by using of hyaluonic acid (HA), a linear polysaccharide of N-acetyl glucosamine and glucuronic acid. To investigate the effect of HA on AH8 penetration, we analyzed paraffin sections of $Micropig^{(R)}$ skin. Fluorescence labeled AH8 was applied to micropig skin with or without HA. The absorption of AH8 was limited to the stratum corneum (SC) without HA. On the other hand, AH8 penetrated to the dermis with HA. Especially, low molecular weight HA (5 kDa) was most efficient compared to 500 kDa HA and 2000 kDa HA. Experiments using fourier-transform infrared (FTIR) spectroscopy revealed that lower molecular weight HA had a tendency to increase the fluidity of the SC lipids more, which means enhancing the skin penetration. Therefore, HA could be expected to enhance the anti-wrinkle effect of AH8.

아세틸 헥사펩타이드 8 (AH8)은 보톡스 메커니즘을 응용한 주름 개선 펩타이드 소재로, 보톡스의 타겟인 synatosomal-associated protein 25 (SNAP25) N말단 서열을 모방하여 개발되었다. 주름 개선 효과가 보고되고 있지만 큰 분자량과 친수성 성질에 의하여 피부 흡수는 잘 되지 않는다는 문제가 있다. 따라서 피부보습 성분 중에서 AH8의 피부 흡수를 증가시켜 줄 수 있는 물질을 탐색하였는데, 히알루론산(HA)이 AH8의 피부 흡수를 증가시켰다. 형광물질로 표지한 AH8만 $Micropig^{(R)}$ skin 에 발라주면 대부분 각질을 투과하지 못하고 각질층에 존재하였다. 반면, HA를 함께 도포한 경우에는 각질층을 투과하여 표피, 진피로 흡수된 AH8가 증가하는 것을 형광 이미지 분석을 통해 확인했다. 특히 5 kDa 저분자량 HA가 500 kDa, 2000 kDa HA보다 피부 흡수를 더 많이 증가시켰다. HA가 피부 각질층에 미치는 영향을 푸리에변환 적외 분광법(Fourier-transform infrared spectroscopy, FTIR)으로 분석해보니, 고분자량 HA는 각질 수분 함량을 증가시키고, 저분자량 HA는 지질층의 유동성을 증가시키는 경향성이 있었다. 따라서 HA는 AH8의 피부 흡수를 증가시켜 주름 개선 효과를 향상시켜 줄 수 있을 것으로 기대된다.

Keywords

HJPHBN_2018_v44n4_447_f0001.png 이미지

Figure 1. Skin delivery of AH8-FITC. (A) The absorption of AH8-FITC to the dermis after applying indicated doses of AH8-FITC (in aqueous solution) was analyzed. The relative penetrations were calculated compared to the 0.1% AH8-FITC treated group (*p < 0.5, ** P < 0.005). (B) The distribution of AH8-FITC in the skin layers after O/N treatment of the peptide.

HJPHBN_2018_v44n4_447_f0002.png 이미지

Figure 2. Increased skin delivery of AH8-FITC by skin hydrating agents. (A,B) After pretreatment of indicated materials, 0.1% of AH8-FITC were applied on MicropigⓇ skin, The relative penetrations to the dermis were calculated compared to the AH8-FITC treated control group (*p < 0.5).

HJPHBN_2018_v44n4_447_f0003.png 이미지

Figure 3. HA enhanced stratum corneum penetration of AH8-FITC. 0.1% AH8-FITC dissolved in 1% HA solution was applied on MicropigⓇ skin (A). The fluorescent intensity in the epidermis and the dermis was analyzed by using imageJ (B).

HJPHBN_2018_v44n4_447_f0004.png 이미지

Figure 4. Penetration enhancing effect of different molecular weight HA. 0.05% AH8-FITC dissolved in 0.5% of indicated molecular weight HA solution was applied on MicropigⓇ skin for O/N.

HJPHBN_2018_v44n4_447_f0005.png 이미지

Figure 5. Interaction of HA with human stratum corneum. Changes of SC skin hydration (A) and lipid chain structure (B) after 4 h application of 1% HA on the forearm.

References

  1. M. Witting, A. Boreham, R. Brodwolf, K. Vavrova, U. Alexiev, W. Friess, and S. Hedtrich, Interactions of hyaluronic acid with the skin and implications for the dermal delivery of biomacromolecules, Mol. Pharm., 12(5), 1391 (2016). https://doi.org/10.1021/mp500676e
  2. C. M. Schoellhammer, D. Blankschtein, and R. Langer, Skin permeabilization for transdermal drug delivery: recent advances and future prospects, Expert Opin. Drug Deliv., 11(3), 393 (2014). https://doi.org/10.1517/17425247.2014.875528
  3. A. Herwadkar and A. K. Banga, Peptide and protein transdermal drug delivery, Drug Discov. Today Technol., 9(2), e147 (2012). https://doi.org/10.1016/j.ddtec.2011.11.007
  4. S. H. Lim, Y. Sun, M. T. Thiruvallur, V. Rosa, and L. Kang, Enhanced skin permeation of anti-wrinkle peptides via molecular modification, Sci. Rep., 8(1), 1596 (2018). https://doi.org/10.1038/s41598-017-18454-z
  5. C. Blanes-Mira, J. Clemente, G. Jodas, A. Gil, G. Fernandez-Ballester, B. Ponsati, L. Gutierrez, E. Perez-Paya, and A. Ferrer-Montiel, A synthetic hexapeptide (argireline) with antiwrinkle activity, Int. J. Cosmet Sci., 24(5), 303 (2002). https://doi.org/10.1046/j.1467-2494.2002.00153.x
  6. M. P. Lupo and A. L. Cole, Cosmeceutical peptides, Dermatol. Ther., 20(5), 343 (2007). https://doi.org/10.1111/j.1529-8019.2007.00148.x
  7. Y. Wang, M. Wang, S. Xiao, P. Pan, P. Li, and J. Huo, The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study, Am. J. Clin. Dermatol., 14(2), 147 (2013). https://doi.org/10.1007/s40257-013-0009-9
  8. M. E. Kraeling, W. Zhou, P. Wang, and O. A. Ogunsola, In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation, Cutan. Ocul. Toxicol., 34(1), 46 (2015). https://doi.org/10.3109/15569527.2014.894521
  9. M. Hoppel, G. Reznicek, H. Kahlig, H. Kotisch, G. P. Resch, and C. Valenta, Topical delivery of acetyl hexapeptide-8 from different emulsions: influence of emulsion composition and internal structure, Eur. J. Pharm. Sci., 68, 27 (2015). https://doi.org/10.1016/j.ejps.2014.12.006
  10. G. Krishnan, M. S. Roberts, J. Grice, Y. G. Anissimov, H. R. Moghimi, and H. A. Benson, Iontophoretic skin permeation of peptides: an investigation into the influence of molecular properties, iontophoretic conditions and formulation parameter, Drug Deliv. Transl. Res., 4(3), 222 (2014). https://doi.org/10.1007/s13346-013-0181-8
  11. Q. D. Pham, S. Bjorklund, J. Engblom, D. Topgaard, and E. Sparr, Chemical penetration enhancers in stratum corneum-relation between molecular effects and barrier function, J. Control Release., 232, 175 (2016). https://doi.org/10.1016/j.jconrel.2016.04.030
  12. I. B. Pathan and C. M. Setty, Chemical penetration enhancers for transdermal drug delivery systems, Trop. J. Pharm. Res., 8(2), 173 (2009).
  13. S. Vikas, S. Seema, S. Gurpreet, A. Rana, and J. Baibhav, Penetration enhancers: a novel strategy for enhancing transdermal drug delivery, Int. Res. J. Pharm., 2(12), 32 (2011).
  14. T. X. Xiang and B. D. Anderson, Phase structures of binary lipid bilayers as revealed by permeability of small molecules, Biochim. Biophys. Acta., 1370(1), 64 (1998). https://doi.org/10.1016/S0005-2736(97)00244-7
  15. A. Carruthers and D. L. Melchior, Study of the relationship between bilayer water permeability and bilayer physical state, Biochemistry, 22, 5797 (1983). https://doi.org/10.1021/bi00294a018
  16. D. T. Downing, Lipid and protein structures in the permeability barrier of mammalian epidermis, J. Lipid Res., 33(3), 301 (1992).
  17. P. W. Wertz, D. C. Swartzendruber, K. C. Madison, and D. T. Downing, Composition and morphology of epidermal cyst lipids, J. Invest. Dermatol., 89(4), 419 (1987). https://doi.org/10.1111/1523-1747.ep12471781
  18. S. Bjorklund, A. Nowacka, J. A. Bouwstra, E. Sparr, and D. Topgaard, Characterization of stratum corneum molecular dynamics by natural-abundance $^{13}C$ solid-state NMR, PLoS ONE, 8(4), e61889 (2013). https://doi.org/10.1371/journal.pone.0061889
  19. S. Stahlberg, B. Skolova, P. K. Madhu, A. Vogel, K. Vavrova, and D. Huster, Probing the role of the ceramide acyl chain length and sphingosine unsaturation in model skin barrier lipid mixtures by $^{2}H$ solid-state NMR spectroscopy, Langmuir., 31(17), 4906 (2015). https://doi.org/10.1021/acs.langmuir.5b00751
  20. E. H. Mojumdar, Q. D. Pham, D. Topgaard, and E. Sparr, Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum, Sci. Rep., 7, 15712 (2017). https://doi.org/10.1038/s41598-017-15921-5
  21. S. Bjorklund, J. M. Andersson, Q. D Pham, A. Nowacka, D. Topgaard, and E. Sparr, Stratum corneum molecular mobility in the presence of natural moisturizers, Soft Matter., 10(25), 4535 (2014). https://doi.org/10.1039/C4SM00137K
  22. J. Voigt and V. R. Driver, Hyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: a systematic review and meta-analysis of randomized controlled trials, Wound Repair Regen., 20(3), 317 (2012). https://doi.org/10.1111/j.1524-475X.2012.00777.x
  23. D. Pirard, P. Vereecken, C. Melot, and M. Heenen, Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses: a meta-analysis of the recent studies, Arch. Dermatol. Res., 297(5), 185 (2005). https://doi.org/10.1007/s00403-005-0601-9
  24. J. Meyer, L. Whitcomb, M. Treuheit, and D. Collins, Sustained in vivo activity of recombinant human granulocyte colony stimulating factor (rHG-CSF) incorporated into hyaluronan, J. Controll. Release., 35(1), 67 (1995). https://doi.org/10.1016/0168-3659(95)00020-9
  25. J. A. Yang, E. S. Kim, J. H. Kwon, H. Kim, J. H. Shin, S. H. Yun, K. Y. Choi, and S. K. Hahn, Transdermal delivery of hyaluronic acid-human growth hormone conjugate, Biomaterials., 33(25), 5947 (2012). https://doi.org/10.1016/j.biomaterials.2012.05.003
  26. S. J. Na, S. Y. Chae, S. Lee, K. Park, K. Kim, J. H. Park, I. C. Kwon, S. Y. Jeong, and K. C. Lee, Stability and bioactivity of nanocomplex of TNF-related apoptosis-inducing ligand, Int. J. Pharm., 363(1-2), 149 (2008). https://doi.org/10.1016/j.ijpharm.2008.07.013
  27. S. H. Lee, S. H. Jun, J. Yeom, S. G. Park, C. K. Lee, and N. G. Kang, Optical clearing agent reduces scattering of light by the stratum corneum and modulates the physical properties of coenocytes via hydration, Skin Res. Technol., 24(3), 371 (2018). https://doi.org/10.1111/srt.12439
  28. A. Z. Chen, L. Q. Chen, S. B. Wang, Y. Q. Wang, and J. Z. Zha, Study of magnetic silk fibroin nanoparticles for massage-like transdermal drug delivery, Int. J. Nanomedicine., 10, 4639 (2015).