Studies of the Physicochemical Properties, Stability, Irritability, and Efficacy of Red Boroco (Celosia argentea) Leaf Extract Patch for Diabetic Wound Healing
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Submitted
30 May 2025
Published
30 June 2026
Keywords:
-
Celosia argentea, Freeze thaw, Patch, physical stability, HET-CAM
Abstract
Red Boroco (Celosia argentea) leaves contain flavonoids that act as wound healers by promoting skin tissue repair and fibroblast growth. The 15% w/w C. argentea leaves extract was formulated into a patch for diabetic wound healing. This study aims to evaluate the physicochemical characteristics, physical stability, irritability, and efficacy of the C. argentea leaves extract patch for diabetic wound healing. Celosia argentea leaves were macerated in 70% ethanol, the flavonoid content was measured, and the extract was formulated into a patch. Evaluation of the patch included measurements of organoleptic properties, pH, weight uniformity, folding resistance, patch thickness, moisture content, and moisture uptake. A stability study was conducted using a freeze-thaw cycle method. The Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) to confirm the irritability of the patch. The efficacy study was conducted by measuring the percentage of wound closure in male Wistar rats. The results showed that C. argentea leaves contained 1.101 ± 0.012 μg QE of flavonoids. The patch characteristics were as follows: pH 6.16 ± 0.01; weight uniformity 0.513 ± 0.038 g; folding resistance >300 folds; patch thickness 0.4 mm; moisture content 0.031 ± 0.028%; and moisture uptake 0.030 ± 0.009%. Statistical analysis (unpaired t-test) showed no significant changes in physical properties after the freeze–thaw cycle (p >0.05), indicating good stability. The one-way ANOVA test of wound closure showed no significant difference between the patch group and the positive control group (p = 0.948). Patch exhibited good physical stability, no irritation, and an 89.88% wound-healing rate in the test animal.
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References
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2. Gao X, Su JF, Wang S, Yang P. Smart Self-Nourishing and Self-Healing Artificial Skin Composite Using Bionic Microvascular Containing Liquid Agent. Polymers. 2022;14(19):3941. DOI: 10.3390/polym14193941.
3. Wang Q, Liu C, An J, Liu J, Wang Y, Cai Y. Mechanisms of microbial infection and wound healing in diabetic foot ulcer: pathogenicity in the inflammatory-proliferative phase, chronicity, and treatment strategies. Front Endocrinol. 2025;16:1657928. DOI: 10.3389/fendo.2025.1657928; PMID: 41103650; PMCID: PMC12520920.
4. Wong WF, Ang KP, Sethi G, Looi CY. Recent Advancement of Medical Patch for Transdermal Drug Delivery. Medicina. 2023;59(4):778. DOI: 10.3390/medicina59040778; PMID: 37109736; PMCID: PMC10142343.
5. Vaseem RS, D'cruz A, Shetty S, Hafsa, Vardhan A, Shenoy SR, et al. Transdermal Drug Delivery Systems: A Focused Review of the Physical Methods of Permeation Enhancement. Adv Pharm Bull. 2024;14(1):67-85. DOI: 10.34172/apb.2024.018; PMID: 38585458; PMCID: PMC10997930.
6. Yan L, Wang Y, Feng J, Ni Y, Zhang T, Cao Y, et al. Mechanism and application of fibrous proteins in diabetic wound healing: a literature review. Front Endocrinol. 2024;15:1430543. DOI: 10.3389/fendo.2024.1430543; PMID: 39129915; PMCID: PMC11309995.
7. Klanrit P, Thanonkeo S, Klanrit P, Klanrit P, Mueangnak K, Thanonkeo P. Celosia argentea: Towards a Sustainable Betalain Source-A Critical Review and Future Prospects. Plants. 2025;14(13):1940. DOI: 10.3390/plants14131940; PMID: 40647948; PMCID: PMC12251642.
8. Guo WZ, Di H, Bao R, Chu GH, Tang XH, Feng M, et al. The healing effect of celosia argentea leaf extract on burn wounds: An in vivo and in vitro evaluation. Int J Clin Exp Med. 2016;9(11):21018-27.
9. Latif MS, Nawaz A, Rashid SA, Akhlaq M, Iqbal A, Khan MJ, et al. Formulation of Polymers-Based Methotrexate Patches and Investigation of the Effect of Various Penetration Enhancers: In Vitro, Ex Vivo and In Vivo Characterization. Polymers. 2022;14(11):2211. DOI: 10.3390/polym14112211; PMID: 35683883; PMCID: PMC9182619.
10. Mo L, Lu G, Ou X, Ouyang D. Formulation and development of novel control release transdermal patches of carvedilol to improve bioavailability for the treatment of heart failure. Saudi J Biol Sci. 2022;29(1):266-72. DOI: 10.1016/j.sjbs.2021.08.088; PMID: 35002418; PMCID: PMC8717168.
11. Sami Alyahya R, AlHasson MA, Ali Alhsaon MA. Assessing the Adverse Effects and Safety Concerns Related to Cosmetic and Skincare Products: A Systematic Review. Cureus. 2025;17(4):e81759. DOI: 10.7759/cureus.81759; PMID: 40330400; PMCID: PMC12051748.
12. Smail SS. Ex Vivo Irritation Evaluation of a Novel Brimonidine Nanoemulsion Using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM). Cureus. 2024;16(8):e68280. DOI: 10.7759/cureus.68280; PMID: 39350816; PMCID: PMC11440450.
13. Almasifard M, Hashemnia M, Cheraghi H, Mohammadalipour A. Esculin improves wound healing in diabetic rats by modulating extracellular matrix remodeling and molecular pathways. Sci Rep. 2026;16(1):7298. DOI: 10.1038/s41598-026-39098-y; PMID: 41639197; PMCID: PMC12923643.
14. Dureshahwar K, Mubashir M, Une HD. Quantification of Quercetin Obtained from Allium cepa Lam. Leaves and its Effects on Streptozotocin-induced Diabetic Neuropathy. Pharmacognosy Res. 2017;9(3):287-93. DOI: 10.4103/pr.pr_147_16; PMID: 28827972; PMCID: PMC5541487.
15. Arilla E, Martínez-Monzó J, Chiş MS, Fǎrcaş AC, Socaci SA, Codoñer-Franch P, et al. Sensory Evaluation, Physico-Chemical Properties, and Aromatic Profile of Pasteurised Orange Juice with Resistant Maltodextrin. Foods. 2023;12(21):4025. DOI: 10.3390/foods12214025; PMID: 37959144; PMCID: PMC10648707.
16. Ramadhan GP, Wahyuningsih I, Widyaningsih W. Development of transdermal patch preparations binahong leaf extract (Anredera cordifolia (Ten.) Steenis) and antihyperglycemia test in rats. Pharmaciana. 2023;13(2):224-31. DOI: 10.12928/pharmaciana.v13i1.24602.
17. Wijaya DP, Mardiyanto, Herlina, Rizki S, Nurhanif, Apriani EF, et al. Formulation and characterization transdermal patches with chitosan-alginate of mangosteen peel (garcinia mangostana l.). J Med Pharm Allied Sci. 2023;12(6):6199-208. DOI: 10.55522/jmpas.V12I6.5661.
18. Schneider LA, Korber A, Grabbe S, Dissemond J. Influence of pH on wound-healing: a new perspective for wound-therapy? Arch Dermatol Res. 2007;298(9):413-20. DOI: 10.1007/s00403-006-0713-x; PMID: 17091276.
19. Ikram M, Gilhotra N, Gilhotra RM. Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology. Adv Biomed Res. 2015;4:239. DOI: 10.4103/2277-9175.168606; PMID: 26682205; PMCID: PMC4673708.
20. Prajapati ST, Patel CG, Patel CN. Formulation and evaluation of transdermal patch of repaglinide. ISRN Pharm. 2011;2011:651909. DOI: 10.5402/2011/651909; PMID: 22389856; PMCID: PMC3263722.
21. Rumondor AC, Wikström H, Van Eerdenbrugh B, Taylor LS. Understanding the tendency of amorphous solid dispersions to undergo amorphous-amorphous phase separation in the presence of absorbed moisture. AAPS PharmSciTech. 2011;12(4):1209-19. DOI: 10.1208/s12249-011-9686-y; PMID: 21927960; PMCID: PMC3225547.
22. Samuel T, Ugwuanyi JO. Moisture Sorption Behaviour and Mould Ecology of Trade Garri Sold in South Eastern Nigeria. Int J Food Sci. 2014;2014:218959. DOI: 10.1155/2014/218959; PMID: 26904621; PMCID: PMC4745493.
23. Bernal-Chávez SA, Romero-Montero A, Hernández-Parra H, Peña-Corona SI, Del Prado-Audelo ML, Alcalá-Alcalá S, et al. Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach. J Biol Eng. 2023;17(1):35. DOI: 10.1186/s13036-023-00353-9; PMID: 37221599; PMCID: PMC10207779.
24. Patel N, Nakrani H, Raval M, Sheth N. Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability. Drug Deliv. 2016;23(9):3712-23. DOI: 10.1080/10717544.2016.1223225; PMID: 27689408.
25. Awaluddin N, Hikmawati H, Pratiwi RI, Awaluddin A. Efektivitas Gel Ekstrak Biji Kelor (Moringa oleifera L.) terhadap Penyembuhan Luka Diabetes Melitus. J Syifa Sci Clin Res. 2024;6(2):234-44. DOI: 10.37311/jsscr.v6i2.28001.
26. Fatimah SF, Farida V, Nuari YR, Viviandhari D, Pertiwi DV. Investigating the Impact of Surfactant and Cosolvent on the Polyphenolic Content in Arumanis Mango Leaf Extract (Mangifera indica L.). J Sains Farm Klin. 2024;11(1):39-47. DOI: 10.25077/jsfk.11.1.39-47.2024.
27. Ranjan RB, Deokule SS. Pharmacognostic and Phytochemical Investigation of Celosia argentea Linn. Int Res J Pharm. 2013;4(6):138-44. DOI: 10.7897/2230-8407.04631.
28. Tran HQ, Shahriar SMS, Yan Z, Xie J. Recent Advances in Functional Wound Dressings. Adv Wound Care. 2023;12(7):399-427. DOI: 10.1089/wound.2022.0059; PMID: 36301918; PMCID: PMC10125407.
29. Zarmpi P, Flanagan T, Meehan E, Mann J, Fotaki N. Biopharmaceutical Understanding of Excipient Variability on Drug Apparent Solubility Based on Drug Physicochemical Properties: Case Study-Hypromellose (HPMC). AAPS J. 2020;22(2):49. DOI: 10.1208/s12248-019-0411-1; PMID: 32072317; PMCID: PMC7028811.
30. Du H, Liu K, Xu T, Xu C, Lin M, Fang Z, et al. Lignocellulosic Films: Preparation, Properties, and Applications. Chem Rev. 2025;125(24):11666-814. DOI: 10.1021/acs.chemrev.5c00267; PMID: 41370747; PMCID: PMC12746420.
31. Dwita LP, Ladeska V, Ramadhani A, Augusta DR, Saufia RT. Manfaat Ekstrak Etanol Daun Remek Daging (Hemigraphis colorata W. Bull) terhadap Luka Bakar pada Tikus. J Tumbuhan Obat Indones. 2020;13(1):32-40. DOI: 10.22435/jtoi.v13i1.2823.
32. Sulaiman AA, Maslachah L, Utama S, Yuniarti WM, Sukmanadi M, Hidajati N. The Effectiveness of Melinjo Leaf (Gnetum gnemon L.) Extract Cream on the Number of Fibroblast Cells in the Second Degree Burn (Deep Partial Thickness) of white rats (Rattus norvegicus). J Pharm Sci. 2025;8(1):216-23. DOI: 10.36490/journal-jps.com.v8i1.693.
33. Oaks RJ, Cindass R. Silver Sulfadiazine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026. NBKID: NBK556054; PMID: 32310514.
34. Almadani YH, Vorstenbosch J, Davison PG, Murphy AM. Wound Healing: A Comprehensive Review. Semin Plast Surg. 2021;35(3):141-4. DOI: 10.1055/s-0041-1731791; PMID: 34526860; PMCID: PMC8432991.
35. Jing SL, Suh EJ, Huang KX, Griffin MF, Wan DC, Longaker MT. Understanding and Advancing Wound Healing in the Era of Multi-Omic Technology. Bioengineering. 2025;13(1):51. DOI: 10.3390/bioengineering13010051; PMID: 41595988; PMCID: PMC12837972.
36. Soewondo P, Suyono S, Sastrosuwignyo MK, Harahap AR, Sutrisna B, Makmun LH. Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in Tertiary Hospital in Indonesia. Acta Med Indones. 2017;49(1):41-51. PMID: 28450653.
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Authors
1.
Fatimah SF, Basuki NS, Efiana NA. Studies of the Physicochemical Properties, Stability, Irritability, and Efficacy of Red Boroco (Celosia argentea) Leaf Extract Patch for Diabetic Wound Healing. Borneo J Pharm [Internet]. 2026Jun.30 [cited 2026Sep.29];9(2):165-78. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/9974
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