SPACE-Peptide succesfully improves dermis penetration of amniotic membrane stem cell metabolite product as antiaging
DOI:
https://doi.org/10.35814/jifi.v24i2.2048Keywords:
AMSCMP, irritation, penetration, SPACE-PeptideAbstract
Amniotic Membrane Stem Cell Metabolite Product (AMSCMP) contains a 75.33 kDa protein, making dermal penetration difficult. The Skin Penetrating and Cell Entering (SPACE) peptide facilitates protein molecule penetration reversibly. This study aimed to assess the penetration depth and skin irritation level of AMSCMP combined with SPACE peptide. In vivo experiments were conducted on mice, evaluating penetration via staining depth and irritation through edema, polymorphonuclear (PMN) cell levels, and tissue degeneration. Penetration results showed distinct fluorescence differences, where formulas with the SPACE peptide (F2, F3, F4) achieved penetration depths exceeding 1,200 μm, whereas the control without SPACE (F1) showed no measurable penetration. Statistical analysis confirmed a significant difference in penetration depth among formulas (p < 0.05), proving that SPACE peptide significantly enhanced active ingredient delivery into the skin. Regarding skin safety, F1 and F2 showed an irritation index of zero (no irritation), while F3 and F4 yielded a score of 1.3, falling into the very mild irritation category. However, statistical analysis revealed no significant difference in irritation scores across all formulations (p > 0.05), indicating that the addition of SPACE peptide did not induce meaningful skin irritation. Conclusion: The addition of SPACE peptide significantly enhances the skin penetration of AMSCMP while maintaining an exceptionally mild, non-significant irritation profile suitable for topical application.
References
[1] Z. Lotfollahi, “The anatomy, physiology and function of all skin layers and the impact of ageing on the skin,” Mar. 01, 2024, Cambridge Media. Vol 2024;32(1):6-10.doi: 10.33235/wpr.32.1.6-10.
[2] D. I. K. Sari, T. Erawati, A. Miatmoko, C. R. S. Prakoeswa, and W. Soeratri, “Characterization and Stability Study of Amniotic Membrane Stem Cell Metabolite Product (AMSC-MP),” International Journal of Pharma Research and Health Sciences, vol. 8, no. 1, pp. 3126–3130, Feb. 2020, doi: 10.21276/ijprhs.2020.01.02.
[3] Y. Kang et al., “Nanocarrier-Based Transdermal Drug Delivery Systems for Dermatological Therapy,” Nov. 01, 2024, Multidisciplinary Digital Publishing Institute (MDPI). 2024 Oct 28;16(11):1384 doi: 10.3390/pharmaceutics16111384.
[4] E. Cristhian Lima de Oliveira et al., “Navigating in the chemical space of peptides: computational strategies and molecular features to unveil their functional and drug-like properties,” May 20, 2026, Royal Society of Chemistry. (2026) Vol.28, no.19 :pp 11519–11545. doi: 10.1039/d5cp04611d.
[5] J. Xie et al., “Cell-Penetrating Peptides in Diagnosis and Treatment of Human Diseases: From Preclinical Research to Clinical Application,” May 20, 2020, Frontiers Media S.A. Vol.11, pp.1-23 doi: 10.3389/fphar.2020.00697.
[6] A. M. Jankowski, M. A. Ensign, and K. Maisel, “Cell-penetrating peptides as facilitators of cargo-specific nanocarrier-based drug delivery,” Sep. 11, 2025, Royal Society of Chemistry. Vol.17, pp. 20006-20019 doi: 10.1039/d5nr00617a.
[7] E. Touitou, H. Natsheh, and J. Zailer, “Film Forming Systems for Delivery of Active Molecules into and across the Skin,” Pharmaceutics, vol. 15, no. 2, pp.1-19 Feb. 2023, doi: 10.3390/pharmaceutics15020397.
[8] S. H. Lim, Y. Sun, T. Madanagopal Thiruvallur, V. Rosa, and L. Kang, “Enhanced Skin Permeation of Anti-wrinkle Peptides via Molecular Modification,” Sci. Rep., vol. 8, no. 1, Dec. 2018, doi: 10.1038/s41598-017-18454-z.
[9] N. van Walraven, R. J. FitzGerald, H. J. Danneel, and M. Amigo-Benavent, “Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence,” Nov. 01, 2025, Elsevier Inc. Vol.193,pp.1-26 doi: 10.1016/j.peptides.2025.171440
[10] M. S. Martins, M. S. Ferreira, I. F. Almeida, and E. Sousa, “Occurrence of Allergens in Cosmetics for Sensitive Skin,” Cosmetics, vol. 9, no. 2, Apr. 2022, doi: 10.3390/cosmetics9020032.
[11] S. Kumari, T. D. Atem, V. Chaudhary, S. K. Sahu, and B. Pal, “Prevalence and risk factors of cosmetic-induced adverse events: A systematic review and meta-analysis,” 2024, Open Science Publishers LLP Inc. Vol. 14 (11), pp.252-263 doi: 10.7324/JAPS.2024.193512.
[12] D. I. S. P. Resende, M. S. Ferreira, J. M. Sousa-Lobo, E. Sousa, and I. F. Almeida, “Usage of synthetic peptides in cosmetics for sensitive skin,” Pharmaceuticals, vol. 14, no. 8, Aug. 2021, doi: 10.3390/ph14080702.
[13] J. Lee et al., “Cell-penetrating peptides enhance the activity of human fibroblast growth factor 2 by prolonging the retention time: A new vision for drug-delivery systems,” Int. J. Mol. Sci., vol. 21, no. 2, Jan. 2020, doi: 10.3390/ijms21020442.
[14] Q. M. Qi, M. Duffy, A. M. Curreri, J. P. R. Balkaran, E. E. L. Tanner, and S. Mitragotri, “Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery,” Adv. Funct. Mater., vol. 30, no. 45, Nov. 2020, doi: 10.1002/adfm.202004257.
[15] J. Chen, C. Liu, Y. Yang, X. Gong, and H. Qian, “The stratum corneum barrier: impaired function in relation to associated lipids and proteins,” 2025, Taylor and Francis Ltd. vol.13, no. 2, pp.1-12 doi: 10.1080/21688370.2024.2361197.
[16] R. Lei et al., “Adult stem cell therapy for skin wound healing: A translational perspective from bench to bedside,” Regenesis Repair Rehabilitation, Sep. 2026, vol.2, no.3, pp.235-258 doi: 10.1016/j.rerere.2026.06.003.
[17] Y. Li et al., “Targeting skin barrier repair: mechanisms of action, therapeutic evidence, and clinical translation challenges of mesenchymal stem cell-derived exosomes,” Stem Cell Res. Ther., May 2026, vol.17 no.250, pp. 1-16 doi: 10.1186/s13287-026-04941-6.
[18] L. Chen et al., “Inflammatory responses and inflammation-associated diseases in organs,” oncotarget. 2018. Vol.9, no. 6, pp.7204-7218. Doi: 10.18632/oncotarget.23208
[19] “OECD (2025), Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264242845-en.
[20] Patel K, Nixon R. Irritant Contact Dermatitis - a Review. Curr Dermatol Rep. 2022;11(2):41-51. doi: 10.1007/s13671-021-00351-4. Epub 2022 Apr 7. PMID: 35433115; PMCID: PMC8989112.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 JURNAL ILMU KEFARMASIAN INDONESIA

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Licencing
All articles in Jurnal Ilmu Kefarmasian Indonesia are an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted non-commercial used, distribution and reproduction in any medium.
This licence applies to Author(s) and Public Reader means that the users mays :
- SHARE:
copy and redistribute the article in any medium or format - ADAPT:
remix, transform, and build upon the article (eg.: to produce a new research work and, possibly, a new publication) - ALIKE:
If you remix, transform, or build upon the article, you must distribute your contributions under the same license as the original. - NO ADDITIONAL RESTRICTIONS:
You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
It does however mean that when you use it you must:
- ATTRIBUTION: You must give appropriate credit to both the Author(s) and the journal, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
You may not:
- NONCOMMERCIAL: You may not use the article for commercial purposes.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.












