Challenges and strategies for collagen delivery for tissue regeneration


  • Lia Agustina Doctoral Program of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Department of Pharmacy, Faculthy of Pharmacy, Institut Ilmu Kesehatan Bhakti Wiyata, Kediri
  • Andang Miatmoko Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya
  • Dewi Melani Hariyadi Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya



Collagen, Oral, Topical, Scoping review, Tissue regeneration


Background: Aged skin is characterized by wrinkles, hyperpigmentation, and roughness. Collagen is the most abundant protein in our body and it’s responsible for skin health and it’s mostly influenced by factors that accelerated aging such as UV.

Objective: This study aimed to identify the potential use of collagen as skin supplementation and the challenges and strategies for its delivery.

Methods: The articles were first searched through the existing database with the keyword of “collagen antiaging”. The 585 articles were then screened by year of publication (2012-2022) resulted in 475 articles. The articles were then selected based on the delivery of collagen either orally or topically, resulted in 12 articles for further analysis.

Results: Collagen has important roles in skin physiology by involving some mechanisms through inhibition of Mitogen-Activated Protein Kinase, induction of Tissue Growth Factor β (TGF-β), and inhibition of Nuclear Factor kappa beta (NF-κβ). The oral administration of collagen has an effective biological activity but requires large doses (up to 5 g daily). Meanwhile, the topical administration of collagen is limited by poor permeability due to high molecular weight (±300 kDa). Several strategies need to be carried out mainly by physical modification such as hydrolyzed collagen or entrapment of collagen using a suitable delivery system.

Conclusions: Collagen could improve the skin properties, but further research should be conducted to increase its penetration either by physical modification or entrapment into suitable carrier.

Download data is not yet available.


Champion RH, Rook A, Burton JL, et al. Textbook of Dermatology. Oxford, UK: Blackwell Scientific 1992.

Ansary TM, Hossain MR, Kamiya K, et al. Inflammatory molecules associated with ultraviolet radiation mediated skin aging. Int. J. Mol. Sci. 202:3974. DOI:

Tsatsou F, Trakatelli M, Patsatsi A, et al. Extrinsic aging: UV-mediated skin carcinogenesis, Dermatoendocrinology 2012:285–97. DOI:

Amaro-Ortiz A, Yan B, D'Orazio JA. Ultraviolet radiation, aging and the skin: prevention of damage by topical cAMP manipulation. Molecules 2014;19:6202–19. DOI:

Baumann L. How to use oral and topical cosmeceuticals to prevent and treat skin aging. Facial Plast Surg Clin N Am 2018:407-13. DOI:

Liu Y, Su G, Zhou F, et al. Protective effect of bovine elastin peptides against photoaging in mice and identification of novel antiphotoaging peptides. J Agric Food Chem 2018:10760–8. DOI:

Cao C, Xiao Z, Tong H, et al. Oral Intake of chicken bone collagen peptides anti-skin aging in mice by regulating collagen degradation and synthesis, inhibiting inflammation and activating lysosomes, Nutrients 2022;14:1622. DOI:

Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science 1996;273:59-63. DOI:

Hensley K, Floyd R. Reactive oxygen species and protein oxidation in aging: a look back, a look ahead. Arch Biochem Biophys 2002;397:377-83. DOI:

Chamougrand N, Rigoulet M. Aging and oxidative stress: studies of some genes involved both in aging and in response to oxidative stress. Respir Physiol 2001;128:393-401. DOI:

Ma W, Wlaschek M, Tantcheva-Poor I, et al., Chronological aging and photoaging of the fibroblasts and the dermal connective tissue. Clin Exp Dermatol 2001;26 :592-99. DOI:

Herman D. Aging: overview. Ann N Y Acad Sci 2001;928:1-21. DOI:

Sibilla S, Godfrey M, Brewer S, et al. An overview of the beneficial effects of hydrolysed collagen as a nutraceutical on skin properties: scientific background and clinical studies. Open Nutraceuticals J 2015;8:29-42. DOI:

Poltavets V, Kochetkova M, Pitson SM, Samuel MS, The role of the extracellular matrix and its molecular and cellular regulators in cancer cell plasticity. Front Oncol 2018;8:431. DOI:

Ganceviciene R, Liakou AI, Theodoridis A, et al. Skin anti-aging strategies. Dermatoendocrinol 2012;4:308-19. DOI:

Asserin J, Lati E, Shioya T, Prawitt J. The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: Evidence from an ex vivo model and randomized, placebo controlled clinical trials, J Cosmet Dermatol 2015;14:291-301. DOI:

Sato K, The presence of food-derived collagen peptides in human body-structure and biological activity, Food Funct 2017;8:4325-30. DOI:

Yamada H, Nagaoka M, Terajima N, et al. Effects of fish collagen peptides on collagen post-translational modifications and mineralization in an osteoblastic cell culture system, Dent Mater J 2013;32:88-95. DOI:

Ito N, Seki S, and Ueda F. Effects of composite supplement containing collagen peptide and ornithine on skin conditions and plasma IGF-1 levels—a randomized, double-blind, placebo-controlled trial, Marine Drugs 2018;16:482. DOI:

Laing S, Bielfeldt S, Ehrenberg C, Wilhelm KP. A dermonutrient containing special collagen peptides improves skin structure and function: a randomized, placebo-controlled, triple-blind trial using confocal laser scanning microscopy on the cosmetic effects and tolerance of a drinkable collagen supplement, J Med Food 2020;23:147-52. DOI:

Lee YI, Lee SG, Jung I, et al. Effect of a topical collagen tripeptide on antiaging and inhibition of glycation of the skin: A pilot study. Int J Mol Sci 2022;23:1101. DOI:

De Luca C, Mikhal’chik EV, Suprun MV, et al. Skin antiageing and systemyc redox effect of supplementation with marine collagen peptides and plant-derived antioxidants: a single-blind case-control clinical study, Oxidative Medicine and Cellular Longevity 2016;14:2016. DOI:

Proksch E, Segger D, Degwert J, et al., Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol 2014;27:47-55. DOI:

Iwai K, Hasegawa T, Taguchi Y, et al., Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates. J Agric Food Chem 2005;53:6531-36. DOI:

Sai Y, Kajita M, Tamai I, et al., Adsorptive mediated endocytosis of a basic peptide in enterocyte-like Caco-2 cells. Am J .Physiol 1998;275:23. DOI:

Zhu Z, Yang G, Wang Y, et al. Suppression of thioredoxin system contributes to silica-induced oxidative stress and pulmonary fibrogenesis in rats, Toxicology Letters 2013;222:289-94. DOI:

Zhou CF, Yu JF, Zhang JX. N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma, Clin Exp Dermatol 2013;38:403–9. DOI:

Cooper SK, Pandhare J, Donald SP, Phang JM. A novel function for hydroxyproline oxidase in apoptosis through generation of reactive oxygen species, J Biol Chem 2008;283:10485-92. DOI:

Leon-Lopez A, Fuentes-Jimenez L. Hernandez-Fuentes AD, et al., Hydrolysed collagen from sheepskins as a source of functional peptides with antioxidant activity. Int. J. Mol. Sci 2019,20:3931. DOI:

Chalamaiah M, Dinesh KB, Hemalatha R, Jyothirmayi T. Fish protein hydrolysates: proximate composition, amino acid composition, antioxidant activities and applications—a review, Food Chemistry 2012;135:3020-38. DOI:

Altenhöfer S, Radermacher KA, Kleikers PW, et al. Evolution of NADPH oxidase inhibitors: selectivity and mechanisms for target engagement, Antioxid Redox Signal 2015;23:406-27. DOI:

Ott C, Jacobs K, Haucke E, et al. Role of advanced glycation end products in cellular signaling, Redox Biol 2014;2:411-29. DOI:

Adson A, Raub TJ, Burton PS, et al. Quantitative approaches to delineate paracellular diffusion in cultured epithelial cell monolayers. J Pharm Sci 1994;83:1529–36. DOI:

Watanabe-Kamiyama M, Shimizu M, Kamiyama S, et al. Absorption and effectiveness of orally administered low molecular weight collagen hydrolysate in rats. J Agric Food Chem 2010;58:835-41. DOI:

Baert B, Deconinck E, Gele MV, et al. Transdermal penetration behavior of drugs: CART clustering, QSPR, and selection of model compounds. Bioorg Med Chem 2007;15:6943-55. DOI:

Chai HJ, Li JH, Huang HN, et al. Effects of size and conformations of fish-scale collagen peptides in facial skin qualities and transdermal penetration efficiency, J Biomed Biotechnol 2010;2010:757301. DOI:

Lephart ED, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res Rev 2016;31:36-54. DOI:

Reilliy DM, Lozano J. Skin collagen through the lifestages: importance for skin health and beauty. Plastic Aesthetic Res 2020;2021. DOI:

Freitas-Rodríguez S, Folgueras AR, López-Otín C, The role of matrix metalloproteinases in aging: Tissue remodeling and beyond, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2017;1864:2015-25. DOI:




How to Cite

Agustina, L., Miatmoko, A., & Hariyadi, D. M. (2023). Challenges and strategies for collagen delivery for tissue regeneration. Journal of Public Health in Africa, 14(s1).