Capsaicin Hydrogel Skin Patch: Development, Characterization, and Safety Evaluation of Cytotoxicity, Anti-Inflammatory Effects, and Pain-Relief Applications

ORIGINAL ARTICLE
Chutharat Thanchonnang, Alisa Boonsuya, Phornpitcha Pechdee, Patpicha Arunsan, Nav La, Nattawut Keeratibharat, Nathkapach Kaewpitoon Rattanapitoon, Wiwat Nuansing, Schawanya Kaewpitoon Rattanapitoon

 
For citation: Thanchonnang C, Boonsuya A, Pechdee P, Arunsan P, la N, Keeratibharat N, Rattanapitoon NK, Nuansing W, Rattanapitoon SK. Capsaicin Hydrogel Skin Patch: Development, Characterization, and Safety Evaluation of Cytotoxicity, Anti-Inflammatory Effects, and Pain-Relief Applications. International Journal of Biomedicine. 2025;15(3):572-582. doi:10.21103/Article15(3)_OA19
 
Originally published September 5, 2025

Abstract: 

Background: Capsaicin, the primary pungent component of Capsicum annuum, exhibits significant anti-inflammatory and analgesic properties by acting on TRPV1 receptors and modulating COX-2 expression. However, its therapeutic use is limited by poor solubility, instability, and potential skin irritation. Myofascial Pain Syndrome (MPS), a prevalent musculoskeletal disorder, presents a need for safer and more effective topical treatments. This study aimed to develop and evaluate capsaicin loaded hydrogel patches for cytotoxic effects, anti-inflammatory properties, and pain relief.
Methods and Results: A hydrogel patch containing 0.1% capsaicin was fabricated using polyvinyl alcohol (PVA), gelatin, glycerol, Tween 80, triethanolamine through the freeze–thaw technique. Structural analysis by GC-MS revealed bioactive constituents, predominantly dodecyl acrylate (45.78%), oleic acid (25.06%), and trans-oleic acid (7.52%), all known for their anti-inflammatory and skin-permeation-enhancing properties. FTIR confirmed the successful incorporation of capsaicin into the hydrogel matrix with characteristic shifts in N–H, C=O, and C–N functional groups, while UV-Vis spectroscopy supported capsaicin release over time. Cytotoxicity testing on human skin fibroblast (HSF) cells demonstrated high cell viability (>90%) at concentrations below 1 mg/mL, with an IC₅₀ of approximately 20 mg/mL, indicating low toxicity at therapeutic doses. The hydrogel exhibited dose-dependent anti-inflammatory activity. Notably, the anti-inflammatory efficacy was statistically comparable to diclofenac (P = 0.183).
Conclusion: The capsaicin-loaded hydrogel patch showed excellent physicochemical characteristics, structural stability, and biocompatibility. Its anti-inflammatory efficacy was on a par with standard diclofenac, supporting its potential as a safe and effective treatment for localized pain and inflammation management with MPS.

Keywords: 
anti-inflammatory activity • Capsaicin • cytotoxicity • myofascial pain
References: 
  1. Kobata K, Todo T, Yazawa S, Iwai K, Watanabe T. Novel Capsaicinoid-like Substances, Capsiate and Dihydrocapsiate, from the Fruits of a Nonpungent Cultivar, CH-19 Sweet, of Pepper (Capsicum annuum L.). J Agric Food Chem.. 1998;46(5):1695-7. doi: 10.1021/jf980135c.
  2. Ahmad R, Alqathama A, Aldholmi M, Riaz M, Abdalla AN, Mostafa A, Al-Said HM, Alqarni AM, Ullah R, Asgher SS, Amir M, Shaaban H, Ahmad W. Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Profiling and Biological Activities of Various Capsicum annum cultivars. Plants (Basel). 2022 Apr 9;11(8):1022. doi: 10.3390/plants11081022. PMID: 35448750; PMCID: PMC9025676.
  3. Paradossi G, Cavalieri F, Chiessi E, Spagnoli C, Cowman MK. Poly(vinyl alcohol) as versatile biomaterial for potential biomedical applications. J Mater Sci Mater Med. 2003 Aug;14(8):687-91. doi: 10.1023/a:1024907615244. PMID: 15348409.
  4. Jeszka-Skowron M, Zgoła-Grześkowiak A, Grześkowiak T, Ramakrishna A. Analytical Methods in the Determination of Bioactive Compounds and Elements in Food: Springer; 2021.
  5. Huang CJ, Pu CM, Su SY, Lo SL, Lee CH, Yen YH. Improvement of wound healing by capsaicin through suppression of the inflammatory response and amelioration of the repair process. Mol Med Rep. 2023 Aug;28(2):155. doi: 10.3892/mmr.2023.13042. Epub 2023 Jun 30. PMID: 37387413; PMCID: PMC10350740.
  6. Benítez-Angeles M, Morales-Lázaro SL, Juárez-González E, Rosenbaum T. TRPV1: Structure, Endogenous Agonists, and Mechanisms. Int J Mol Sci. 2020 May 12;21(10):3421. doi: 10.3390/ijms21103421. PMID: 32408609; PMCID: PMC7279265.
  7. Li Z, Zhang J, Cheng K, Zhang L, Wang T. Capsaicin alleviates the intestinal oxidative stress via activation of TRPV1/PKA/UCP2 and Keap1/Nrf2 pathways in heat-stressed mice. Journal of Functional Foods. 2023;108:105749. doi: 10.1016/j.jff.2023.105749.
  8. Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA. Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. Molecules. 2016 Jun 28;21(7):844. doi: 10.3390/molecules21070844. PMID: 27367653; PMCID: PMC6273101.
  9. Chuang YC, Yoshimura N, Huang CC, Wu M, Chiang PH, Chancellor MB. Intraprostatic botulinum toxin a injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat. J Urol. 2008 Aug;180(2):742-8. doi: 10.1016/j.juro.2007.07.120. Epub 2008 Jun 13. PMID: 18554636.
  10. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997 Oct 23;389(6653):816-24. doi: 10.1038/39807. PMID: 9349813.
  11. Shahsavari F, Abbasnejad M, Esmaeili-Mahani S, Raoof M. The ability of orexin-A to modify pain-induced cyclooxygenase-2 and brain-derived neurotrophic factor expression is associated with its ability to inhibit capsaicin-induced pulpal nociception in rats. Korean J Pain. 2022 Jul 1;35(3):261-270. doi: 10.3344/kjp.2022.35.3.261. PMID: 35768981; PMCID: PMC9251390.
  12. Appasamy M, Lam C, Alm J, Chadwick AL. Trigger Point Injections. Phys Med Rehabil Clin N Am. 2022 May;33(2):307-333. doi: 10.1016/j.pmr.2022.01.011. PMID: 35526973; PMCID: PMC9116734.
  13. Wilke J, Vogt L, Niederer D, Hübscher M, Rothmayr J, Ivkovic D, Rickert M, Banzer W. Short-term effects of acupuncture and stretching on myofascial trigger point pain of the neck: a blinded, placebo-controlled RCT. Complement Ther Med. 2014 Oct;22(5):835-41. doi: 10.1016/j.ctim.2014.09.001. Epub 2014 Sep 16. PMID: 25440373.
  14. Romero V, Lara JR, Otero-Espinar F, Salgado MH, Modolo NSP, Barros GAM. Creme tópico de capsaicina (8%) para o tratamento da síndrome da dor miofascial [Capsaicin topical cream (8%) for the treatment of myofascial pain syndrome]. Braz J Anesthesiol. 2019 Sep-Oct;69(5):432-438. doi: 10.1016/j.bjan.2019.06.008. Epub 2019 Sep 10. PMID: 31519301; PMCID: PMC9391859.
  15. Quintner JL, Bove GM, Cohen ML. A critical evaluation of the trigger point phenomenon. Rheumatology (Oxford). 2015 Mar;54(3):392-9. doi: 10.1093/rheumatology/keu471. Epub 2014 Dec 3. PMID: 25477053.
  16. Chen Y, Li J, Lu J, Ding M, Chen Y. Synthesis and properties of Poly(vinyl alcohol) hydrogels with high strength and toughness. Polymer Testing. 2022;108:107516. doi: 10.1016/j.polymertesting.2022.107516.
  17. Boriwanwattanarak P, Ingkaninan K, Khorana N, Viyoch J. Development of curcuminoids hydrogel patch using chitosan from various sources as controlled-release matrix. Int J Cosmet Sci. 2008 Jun;30(3):205-18. doi: 10.1111/j.1468-2494.2008.00437.x. PMID: 18452437.
  18. Sun X, Agate S, Salem KS, Lucia L, Pal L. Hydrogel-Based Sensor Networks: Compositions, Properties, and Applications-A Review. ACS Appl Bio Mater. 2021 Jan 18;4(1):140-162. doi: 10.1021/acsabm.0c01011. Epub 2020 Nov 17. PMID: 35014280.
  19. Kim GJ, Kim KO. Novel glucose-responsive of the transparent nanofiber hydrogel patches as a wearable biosensor via electrospinning. Sci Rep. 2020 Nov 2;10(1):18858. doi: 10.1038/s41598-020-75906-9. PMID: 33139822; PMCID: PMC7608638.
  20. Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998 Nov 1;18(21):8947-59. doi: 10.1523/JNEUROSCI.18-21-08947.1998. PMID: 9787000; PMCID: PMC6793545.
  21. Ilie MA, Caruntu C, Tampa M, Georgescu SR, Matei C, Negrei C, Ion RM, Constantin C, Neagu M, Boda D. Capsaicin: Physicochemical properties, cutaneous reactions and potential applications in painful and inflammatory conditions. Exp Ther Med. 2019 Aug;18(2):916-925. doi: 10.3892/etm.2019.7513. Epub 2019 Apr 19. PMID: 31384324; PMCID: PMC6639979.
  22. Jaiboonma A, Kaokaen P, Chaicharoenaudomrung N, Kunhorm P, Janebodin K, Noisa P, Jitprasertwong P. Cordycepin attenuates Salivary Hypofunction through the Prevention of Oxidative Stress in Human Submandibular Gland Cells. Int J Med Sci. 2020 Jul 6;17(12):1733-1743. doi: 10.7150/ijms.46707. PMID: 32714076; PMCID: PMC7378660.
  23. Padmanabhan P, Jangle S. Evaluation of in-vitro anti-inflammatory activity of herbal preparation, a combination of four medicinal plants. Int J Appl Basic Med Res. 2012;2(1):109-16.
  24. Marius M, Amadou D, Donatien AA, Gilbert A, William YN, Rauf K, Arif M, Adeline FYS, Saint NI, Dar H, Rehman NU, Ahmad I. In Vitro Antioxidant, Anti-inflammatory, and In Vivo Anticolitis Effects of Combretin A and Combretin B on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice. Gastroenterol Res Pract. 2020 Nov 7;2020:4253174. doi: 10.1155/2020/4253174. PMID: 33204254; PMCID: PMC7666632.
  25. Viechtbauer W, Smits L, Kotz D, Budé L, Spigt M, Serroyen J, Crutzen R. A simple formula for the calculation of sample size in pilot studies. J Clin Epidemiol. 2015 Nov;68(11):1375-9. doi: 10.1016/j.jclinepi.2015.04.014. Epub 2015 Jun 6. PMID: 26146089.
  26. Tseng C-H, Sim D. Sample size planning for pilot studies. arXiv preprint arXiv:210505483. 2021.
  27. Katz J, Melzack R. Measurement of pain. Surg Clin North Am. 1999 Apr;79(2):231-52. doi: 10.1016/s0039-6109(05)70381-9. PMID: 10352653.
  28. Koleva-Gudeva L, Mitrev S, Maksimova V, Spasov D. Content of capsaicin extracted from hot pepper (Capsicum annuum ssp. microcarpum L.) and its use as an ecopesticide. Hemijska Industrija. 2013;67(4):671-5.
  29. López Pacheco MA, Báez Rojas JJ, Castro-Ramos J, Villa Manríquez JF, Esmonde-White K. Optical study to identify and quantify capsaicin in optical window. Heliyon. 2021 Mar 17;7(3):e05797. doi: 10.1016/j.heliyon.2020.e05797. PMID: 33768170; PMCID: PMC7980067.
  30. Amruthraj NJ, Preetam Raj JP, Lebel A. Capsaicin-capped silver nanoparticles: its kinetics, characterization and biocompatibility assay. Appl. Nanosci. 2015;5(4):403-9. doi: 10.1007/s13204-014-0330-5.
  31. Ko JA, Kim J, Doh H, Park HJ. Quality evaluation and storage test for capsaicin-fortified yogurt based on the multilayer nanoemulsion system. Food Sci Biotechnol. 2023 Jul 28;33(2):441-451. doi: 10.1007/s10068-023-01386-y. PMID: 38222921; PMCID: PMC10786756.
  32. Sancho R, Lucena C, Macho A, Calzado MA, Blanco-Molina M, Minassi A, Appendino G, Muñoz E. Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent antiinflammatory compound in vivo. Eur J Immunol. 2002 Jun;32(6):1753-63. doi: 10.1002/1521-4141(200206)32:6<1753::AID-IMMU1753>3.0.CO;2-2. PMID: 12115659.
  33. Amantini C, Ballarini P, Caprodossi S, Nabissi M, Morelli MB, Lucciarini R, Cardarelli MA, Mammana G, Santoni G. Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis. 2009 Aug;30(8):1320-9. doi: 10.1093/carcin/bgp138. Epub 2009 Jun 5. PMID: 19502594.
  34. Shah M, Parveen Z, Khan MR. Evaluation of antioxidant, anti-inflammatory, analgesic and antipyretic activities of the stem bark of Sapindus mukorossi. BMC Complement Altern Med. 2017 Dec 8;17(1):526. doi: 10.1186/s12906-017-2042-3. PMID: 29221478; PMCID: PMC5723046.
  35. Tshering G, Posadzki P, Kongkaew C. Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: A systematic review and meta-analysis. Phytother Res. 2024 Jul;38(7):3695-3705. doi: 10.1002/ptr.8223. Epub 2024 May 18. PMID: 38761115.
  36. Goodwin B, Chiplunkar M, Salerno R, Coombs K, Sannoh U, Shah V, Averell N, Al-Shebab U, Janora D. Topical capsaicin for the management of painful diabetic neuropathy: a narrative systematic review. Pain Manag. 2023 May;13(5):309-316. doi: 10.2217/pmt-2023-0006. Epub 2023 Jul 12. PMID: 37435696.
  37. Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011 Oct;107(4):490-502. doi: 10.1093/bja/aer260. Epub 2011 Aug 17. PMID: 21852280; PMCID: PMC3169333.
  38. Kennedy WR, Vanhove GF, Lu SP, Tobias J, Bley KR, Walk D, Wendelschafer-Crabb G, Simone DA, Selim MM. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain. 2010 Jun;11(6):579-87. doi: 10.1016/j.jpain.2009.09.019. Epub 2010 Apr 18. PMID: 20400377.
  39. Macho A, Lucena C, Sancho R, Daddario N, Minassi A, Muñoz E, Appendino G. Non-pungent capsaicinoids from sweet pepper synthesis and evaluation of the chemopreventive and anticancer potential. Eur J Nutr. 2003 Jan;42(1):2-9. doi: 10.1007/s00394-003-0394-6. PMID: 12594536.
  40. Joo JI, Kim DH, Choi JW, Yun JW. Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. J Proteome Res. 2010 Jun 4;9(6):2977-87. doi: 10.1021/pr901175w. PMID: 20359164.
  41. Zhou M, Zhang Q, Huo M, Song H, Chang H, Cao J, Fang Y, Zhang D. The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system. Biomed Pharmacother. 2023 May;161:114516. doi: 10.1016/j.biopha.2023.114516. Epub 2023 Mar 13. PMID: 36921535.
  42. Wong F, Reddy A, Rho Y, Vollert J, Strutton PH, Hughes SW. Responders and nonresponders to topical capsaicin display distinct temporal summation of pain profiles. Pain Rep. 2023 Apr 4;8(3):e1071. doi: 10.1097/PR9.0000000000001071. PMID: 37731476; PMCID: PMC10508395.
  43. Cho JH, Brodsky M, Kim EJ, Cho YJ, Kim KW, Fang JY, Song MY. Efficacy of a 0.1% capsaicin hydrogel patch for myofascial neck pain: a double-blinded randomized trial. Pain Med. 2012 Jul;13(7):965-70. doi: 10.1111/j.1526-4637.2012.01413.x. Epub 2012 Jun 8. PMID: 22681259.
  44. Santos MP, Lemos F, Gomes J, Romão JM, Veiga D. Topical capsaicin 8% patch in peripheral neuropathic pain: Efficacy and quality of life. Br J Pain. 2024 Feb;18(1):42-56. doi: 10.1177/20494637231201502. Epub 2023 Sep 12. PMID: 38344267; PMCID: PMC10851892.
  45. Mavrommatis CI, Argyra E, Vadalouka A, Vasilakos DG. Acupuncture as an adjunctive therapy to pharmacological treatment in patients with chronic pain due to osteoarthritis of the knee: a 3-armed, randomized, placebo-controlled trial. Pain. 2012 Aug;153(8):1720-1726. doi: 10.1016/j.pain.2012.05.005. Epub 2012 Jun 21. PMID: 22727499.

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Received May 18, 2025.
Accepted June 19, 2025.
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