Browse > Article
http://dx.doi.org/10.15230/SCSK.2019.45.2.175

Development of Dermal Transduction Epidermal Growth Factor (EGF) Using A Skin Penetrating Functional Peptide  

Kang, Jin Sun (ProCell R&D Center, ProcellTherapeutics. Inc.)
La, Ha Na (ProCell R&D Center, ProcellTherapeutics. Inc.)
Bak, Sun Uk (ProCell R&D Center, ProcellTherapeutics. Inc.)
Eom, Hyo Jung (ProCell R&D Center, ProcellTherapeutics. Inc.)
Lee, Byung Kyu (ProCell R&D Center, ProcellTherapeutics. Inc.)
Shin, Hee Je (ProCell R&D Center, ProcellTherapeutics. Inc.)
Publication Information
Journal of the Society of Cosmetic Scientists of Korea / v.45, no.2, 2019 , pp. 175-184 More about this Journal
Abstract
The epidermal growth factor (EGF) has a intrinsic function of inducing growth and proliferation of cells through interacting with cell membrane receptors in human epidermis and dermis layer. These functions of EGF are used as a main ingredient for wound healing medicines and anti-aging cosmetics. As a cosmetic ingredient, the EGF has a problem in exhibiting its natural efficacy due to the lack of the ability to penetrate through the stratum corneum, which is known as the skin barrier. In this study, a recombinant human epidermal growth factor ($MTD_{151}-EGF$) fused with the macromolecule transduction domain $(MTD)_{151}$ with the skin penetration ability was developed to improve the skin penetration efficiency of the EGF. Expression of $MTD_{151}-EGF$ was performed in E. coli transformed with a vector encoding the $MTD_{151}-EGF$ gene and then purified. The purified $MTD_{151}-EGF$ was evaluated using cell proliferation assay, cytotoxicity test and skin penetration test by franz diffusion cell assay and artificial skin. Cell proliferation activity of $MTD_{151}-EGF$ purified to high purity of 99% or above was equivalent to the EGF or better, and cytotoxicity was not observed. In addition, the $MTD_{151}-EGF$ showed an excellent penetration efficiency compared to the EGF in the skin penetration test with EGF and $MTD_{151}-EGF$ labeled by FITC in an artificial skin penetration model. Based on the quantitative analysis of the penetrating substance using franz diffusion cell assay, the amount of penetration was about 16 times more than that of EGF. These results can be regarded as an effective alternative to improve the existing physical transdermal penetration method related to the use of various active ingredients for cosmetics.
Keywords
epidermal growth factor; MTD-EGF; recombinant human EGF; macromolecule transduction domain; MTD;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 G. Carpenter and S. Cohen, Receptors and Recognition Series B, ed. R. J. Lefkowitz, 13, 43, Chapman and Hall, London (1981).
2 G. Carpenter and S. Cohen, Epidermal growth factor, Annu. Rev. Biochem., 48, 193 (1979).   DOI
3 D. I. Kim, H. J. Han and S. H. Park, The effect of epidermal growth factor on cell proliferation and its related signal pathways in pig hepatocytes, J. Exp. Biomed. Sci., 12, 249 (2006).
4 C. D. Andl, T. Mizushima, H. Nakagawa, K. Oyama, H. Harada, K. Chruma, M. Herlyn and A. K. Rustgi, Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo, J. Biol. Chem., 278(3), 1824 (2003).   DOI
5 B. C. Park, J. H. Lee, T. G. Kim, and Y. H. Kim, The accelerated epithelization of recombinant epidermal growth factor on partial-thickness skin wounds, Journal of Korean Burn Society, 13(2), 101 (2010).
6 U. S. Patent, 5618544 (1994).
7 M. R. Prausnitz and R. Langer, Transdermal drug delivery, Nat. Biotech., 26(11), 1261 (2008).   DOI
8 A. Eguchi, T. Akuta, H. Okuyama, T. Senda, H. Yokoi, H. Inokuchi, S. Fujita, T. Hayakawa, K. Takeda, M. Hasegawa, and M. Nakanishi, Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells, J. Biol. Chem., 276(28), 26204 (2001).   DOI
9 N. Ye, Y. Lin, J. Pan, S. Liu and P. Rao, PTD mediated protein transduction technology and its application in medical field, Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 28(2), 401(2011).
10 Z. Nemes and P. M. Steinert, Bricks and mortar of the epidermal barrier, Experimental and Molecular medicine, 31(1), 5, (1999).   DOI
11 Korea, WO2008093982 (2008).
12 Korea, WO2013077680 (2013).
13 R. Vanbever and V. Preat, In vivo efficacy and safety of skin electroporation, Adv. Drug Deliv. Rev., 35(1), 77 (1999)   DOI
14 G. K. Menon, New insights into skin structure: scratching the surface, Adv. Drug Deliv. Rev., 54(Suppl. 1), S3 (2002).   DOI
15 T. Hikima, S. Ohsumi, K. Shirouzu, and K. Tojo, Mechanisms of Synergistic Skin Penetration by sonophoresis and iontophoresis, Biol. Pharm. Bull., 32(5), 905 (2009).   DOI
16 H. Kalluri and A. K. Banga, Transdermal delivery of proteins, AAPS PharmSciTech, 12(1), 431 (2011).   DOI
17 R. Bhagam, K. Nagaiah, P. Parvathi and L. Narasu, Simple two steps purification of rh-epidermal growth factor expressed in E.coli, Res. J. Pharm. Sci. Biotech, 1(2), 35 (2011).
18 B. A. Jorge, G. C. Jorge, L. S. Pedro, G. L. Tania, C. S. Maria D, L. M. Ernesto, G. N. Gerardo and H. M. Luis, Epidermal growth factor in clinical practice - a review of its biological actions, clinical indications and safety implications, Int Wound J., 6(5), 331 (2009).   DOI
19 J. H. Lim, J. H. Kim, J. S. Kang and D. W. Jo, Partial somatic to stem cell transformations induced by cell-permeable reprogramming factors, Sci Rep, 4, 4361 (2014).
20 Ministry of Food and Drug Safety, Notice No 2006-6, Regulations for the designation of raw materials for cosmetics (2006).
21 J. H. Lim, T. Duong, G. W. Lee, B. L. Seong, W. El-Rifai, H. E. Ruley and D. W. Jo, The effect of intracellular protein delivery on the anti-tumor activity of recombinant human endostatin, Biomaterials, 34(26), 6261 (2013).   DOI
22 J. H. Lim, J. E. Kim, T. Duong, G. W. Lee, J. H. Kim, J. N. Yoon, J. T. Kim, H. C. Kim, H. E. Ruley, W. El-Rifai and D. W. Jo, Antitumor activity of cell-permeable p18(INK4c) with enhanced membrane and tissue penetration, Mol. Ther., 20(8), 1540 (2012).   DOI
23 H. C. Kang, S. D. Ahn, D. H. Choi, M. K. Kang, W. K. Chung, and H. G. Wu, The safety and efficacy of EGF-based cream for the prevention of radiotherapy-induced skin injury: results from a multicenter observational study, Radiat Oncol J, 32(3), 156 (2014).   DOI
24 J. H. Lim, T. Duong, N. Do, P. Do, J. T. Kim, H. C. Kim, W. El-Rifai, H. E. Ruley and D. W. Jo, Antitumor activity of cell-permeable RUNX3 protein in gastric cancer cells, Clin. Cancer Res., 19(3), 680 (2012).   DOI
25 J. H. Lim, G. Y. Jang, S. E. Kang, G. W. Lee, T. T. Nga do, T. L. Phuong do, H. C. Kim, W. El-Rifai, H. E. Ruley and D. W. Jo, Cell-permeable NM23 blocks the maintenance and progression of established pulmonary metastasis, Cancer Res., 71(23), 7216 (2011).   DOI
26 D. J. Jeon, S. W. Kim, M. Chetana, D. W. Jo, H. E. Ruley, S. Y. Lin, D. Rabah, J. P. Kinet and H. S. Shin, Observational fear learning involves affective pain system and Cav1.2 $Ca^{2+}$ channels in ACC., Nat. Neurosci., 13(4), 482 (2010).   DOI