Kajian Pengembangan Sediaan Hidrogel untuk Penanganan Ulkus Diabetikum Secara In Vivo dan In Vitro
DOI:
https://doi.org/10.29313/bcsp.v3i2.8974Keywords:
Madu, Hidrogel, Ulkus Diabetikum, In Vitro, In Vivo, Honey, Hydrogel, Diabetic UlcersAbstract
Diabetic ulcers are the most common and rapidly experienced complication of diabetes mellitus. This condition is caused by neuropathy and peripheral arterial disease, leading to bacterial infection, ulceration, or tissue destruction in the foot. Hydrogel is a pharmaceutical formulation developed based on polymer materials that can accelerate healing and reduce complications of diabetic ulcers through autolytic debridement, control ulcer moisture, and facilitate moist wound healing. The addition of honey developed in hydrogel formulations can enhance the healing of diabetic ulcers due to its known antibacterial activity against bacteria commonly found in diabetic ulcers. This study aims to determine the effectiveness of honey-containing hydrogel in the management of diabetic ulcers both in vitro and in vivo. The study is based on a systematic literature review, examining articles obtained from reputable databases that meet the specified inclusion and exclusion criteria. The results of the study show that the development of hydrogel formulations has been proven to be effective in vitro and in vivo in managing diabetic ulcers by inhibiting bacterial infection and accelerating wound healing in animal testing.
Ulkus diabetikum merupakan komplikasi diabetes melitus yang paling umum dan cepat dialami penderitanya. Kondisi ini disebabkan oleh neuropati serta penyakit arteri perifer, sehingga terjadi infeksi bakteri, ulserasi, atau destruksi pada jaringan kaki. Hidrogel merupakan pengembangan sediaan farmasi berbahan dasar polimer yang mampu mempercepat penyembuhan serta mengurangi komplikasi ulkus diabetikum melalui debridasi autolitik, mengontrol kelembaban ulkus, serta memfasilitasi luka untuk mengalami penyembuhan (moist wound healing). Penambahan madu yang dikembangkan dalam sediaan hidrogel mampu meningkatkan penyembuhan ulkus diabetikum karena telah diketahui memiliki aktivitas antibakteri terhadap bakteri yang umum ditemukan pada ulkus diabetikum. Kajian ini bertujuan mengetahui efektivitas hidrogel mengandung madu dalam penanganan ulkus diabetikum secara in vitro dan in vivo. Kajian ini berbasis systematic literature review dengan mengkaji artikel yang diperoleh dari database dengan reputasi baik yang memenuhi kriteria inklusi dan eksklusi yang telah ditetapkan. Hasil kajian menunjukkan bahwa pengembangan sediaan hidrogel terbukti secara in vitro dan in vivo efektif dalam menangani ulkus diabetikum karena mampu menghambat infeksi bakteri serta mempercepat penyembuhan luka pada hewan uji.
References
[2] M. Z. Banday, A. S. Sameer, and S. Nissar, “Pathophysiology of diabetes: An overview,” Avicenna J Med, vol. 10, no. 04, pp. 174–188, Oct. 2020, doi: 10.4103/ajm.ajm_53_20.
[3] S. Li, J. Wang, B. Zhang, X. Li, and Y. Liu, “Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study,” Diabetes Metab J, vol. 43, no. 3, p. 319, 2019, doi: 10.4093/dmj.2018.0060.
[4] K. Papatheodorou, M. Banach, E. Bekiari, M. Rizzo, and M. Edmonds, “Complications of Diabetes 2017,” J Diabetes Res, vol. 2018, pp. 1–4, 2018, doi: 10.1155/2018/3086167.
[5] J. J. Netten et al., “Definitions and criteria for diabetic foot disease,” Diabetes Metab Res Rev, vol. 36, no. S1, Mar. 2020, doi: 10.1002/dmrr.3268.
[6] Dörr, Lucke-Paulig, Vollmer, and Lobmann, “Malignant Transformation in Diabetic Foot Ulcers—Case Reports and Review of the Literature,” Geriatrics, vol. 4, no. 4, p. 62, Nov. 2019, doi: 10.3390/geriatrics4040062.
[7] P. Chadwick, M. Edmonds, J. McCardle, and D. Armstrong, International Best Practice Guidelines: Wound Management in Diabetic Foot Ulcers. Wounds International. London: Wounds International, 2013.
[8] D. G. Armstrong, A. J. M. Boulton, and S. A. Bus, “Diabetic Foot Ulcers and Their Recurrence,” New England Journal of Medicine, vol. 376, no. 24, pp. 2367–2375, Jun. 2017, doi: 10.1056/NEJMra1615439.
[9] D. C. Jupiter, J. C. Thorud, C. J. Buckley, and N. Shibuya, “The impact of foot ulceration and amputation on mortality in diabetic patients. I: From ulceration to death, a systematic review,” Int Wound J, vol. 13, no. 5, pp. 892–903, Oct. 2016, doi: 10.1111/iwj.12404.
[10] M. Polikandrioti et al., “Quality of Life in Diabetic Foot Ulcer: Associated Factors and the Impact of Anxiety/Depression and Adherence to Self-Care,” Int J Low Extrem Wounds, vol. 19, no. 2, pp. 165–179, Jun. 2020, doi: 10.1177/1534734619900415.
[11] C. Weller, C. Weller, and V. Team, “Interactive dressings and their role in moist wound management,” in Advanced Textiles for Wound Care, Elsevier, 2019, pp. 105–134. doi: 10.1016/B978-0-08-102192-7.00004-7.
[12] A. Ramazani and H. Aghahosseini, “The biological properties of hydrogels based on natural polymers,” in Hydrogels Based on Natural Polymers, Elsevier, 2020, pp. 247–269. doi: 10.1016/B978-0-12-816421-1.00009-4.
[13] T. Mitchell, “Use of manuka honey for autolytic debridement in necrotic and sloughy wounds,” Journal of Community Nursing, vol. 32, no. 4, 2018.
[14] P. Molan and T. Rhodes, “Honey: A Biologic Wound Dressing.,” Wounds, vol. 27, no. 6, pp. 141–51, Jun. 2015.
[15] G. M. Kaimkhani et al., “Pattern of Infecting Microorganisms and Their Susceptibility to Antimicrobial Drugs in Patients with Diabetic Foot Infections in a Tertiary Care Hospital in Karachi, Pakistan,” Cureus, Jun. 2018, doi: 10.7759/cureus.2872.
[16] P. Shanmugam, “The Bacteriology of Diabetic Foot Ulcers, with a Special Reference to Multidrug Resistant Strains,” JOURNAL of CLINICAL AND DIAGNOSTIC RESEARCH, 2013, doi: 10.7860/JCDR/2013/5091.2794.
[17] G. Reiber, B. Lipsky, and G. Gibbons, “The burden of diabetic foot ulcers,” The American Journal of Surgery, vol. 176, no. 2, pp. 5S-10S, Aug. 1998, doi: 10.1016/S0002-9610(98)00181-0.
[18] J. L. Mills et al., “The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI),” J Vasc Surg, vol. 59, no. 1, pp. 220-234.e2, Jan. 2014, doi: 10.1016/j.jvs.2013.08.003.
[19] R. Ward, J. Dunn, L. Clavijo, D. Shavelle, V. Rowe, and K. Woo, “Outcomes of Critical Limb Ischemia in an Urban, Safety Net Hospital Population with High WIfI Amputation Scores,” Ann Vasc Surg, vol. 38, pp. 84–89, Jan. 2017, doi: 10.1016/j.avsg.2016.08.005.
[20] G. M. Sundaram, S. Quah, and P. Sampath, “Cancer: the dark side of wound healing,” FEBS J, vol. 285, no. 24, pp. 4516–4534, Dec. 2018, doi: 10.1111/febs.14586.
[21] M. Mama, T. Teshome, and J. Detamo, “Antibacterial Activity of Honey against Methicillin-Resistant Staphylococcus aureus : A Laboratory-Based Experimental Study,” Int J Microbiol, vol. 2019, pp. 1–9, Apr. 2019, doi: 10.1155/2019/7686130.
[22] E. Smaropoulos and N. A. J. Cremers, “Treating severe wounds in pediatrics with medical grade honey: A case series,” Clin Case Rep, vol. 8, no. 3, pp. 469–476, Mar. 2020, doi: 10.1002/ccr3.2691.
[23] C. C. F. Pleeging et al., “Synergistic Antimicrobial Activity of Supplemented Medical-Grade Honey against Pseudomonas aeruginosa Biofilm Formation and Eradication,” Antibiotics, vol. 9, no. 12, p. 866, Dec. 2020, doi: 10.3390/antibiotics9120866.
[24] L. Vandamme, A. Heyneman, H. Hoeksema, J. Verbelen, and S. Monstrey, “Honey in modern wound care: A systematic review,” Burns, vol. 39, no. 8, pp. 1514–1525, Dec. 2013, doi: 10.1016/j.burns.2013.06.014.
[25] N. Al-Waili, K. Salom, and A. A. Al-Ghamdi, “Honey for Wound Healing, Ulcers, and Burns; Data Supporting Its Use in Clinical Practice,” The Scientific World JOURNAL, vol. 11, pp. 766–787, 2011, doi: 10.1100/tsw.2011.78.
[26] K. Brudzynski, K. Abubaker, M. Laurent, and A. Castle, “Re-Examining the Role of Hydrogen Peroxide in Bacteriostatic and Bactericidal Activities of Honey,” Front Microbiol, vol. 2, 2011, doi: 10.3389/fmicb.2011.00213.
[27] K. Hayashi, A. Fukushima, M. Hayashi-Nishino, and K. Nishino, “Effect of methylglyoxal on multidrug-resistant Pseudomonas aeruginosa,” Front Microbiol, vol. 5, Apr. 2014, doi: 10.3389/fmicb.2014.00180.
[28] S. Sharaf and M. E. El-Naggar, “Wound dressing properties of cationized cotton fabric treated with carrageenan/cyclodextrin hydrogel loaded with honey bee propolis extract,” Int J Biol Macromol, vol. 133, pp. 583–591, Jul. 2019, doi: 10.1016/j.ijbiomac.2019.04.065.
[29] A. Muxika, A. Etxabide, J. Uranga, P. Guerrero, and K. de la Caba, “Chitosan as a bioactive polymer: Processing, properties and applications,” Int J Biol Macromol, vol. 105, pp. 1358–1368, Dec. 2017, doi: 10.1016/j.ijbiomac.2017.07.087.
[30] S. K. Saikaly and A. Khachemoune, “Honey and Wound Healing: An Update,” Am J Clin Dermatol, vol. 18, no. 2, pp. 237–251, Apr. 2017, doi: 10.1007/s40257-016-0247-8.
[31] A. Sameh et al., “Bee venom as an alternative for antibiotics against Staphylococcus aureus infections,” Sci Rep, vol. 13, no. 1, p. 6436, Apr. 2023, doi: 10.1038/s41598-023-33536-x.
[32] I. Przybyłek and T. M. Karpiński, “Antibacterial Properties of Propolis,” Molecules, vol. 24, no. 11, p. 2047, May 2019, doi: 10.3390/molecules24112047.
[33] H. Chopra, S. Bibi, S. Kumar, M. S. Khan, P. Kumar, and I. Singh, “Preparation and Evaluation of Chitosan/PVA Based Hydrogel Films Loaded with Honey for Wound Healing Application,” Gels, vol. 8, no. 2, p. 111, Feb. 2022, doi: 10.3390/gels8020111.
[34] L. Sasikala, R. Rathinamoorthy, and B. Dhurai, “Optimization of process conditions for chitosan-manuka honey film as wound contact layer for wound dressings,” Wound Medicine, vol. 23, pp. 11–21, Dec. 2018, doi: 10.1016/j.wndm.2018.09.007.
[35] M. J. Afshari, N. Sheikh, and H. Afarideh, “PVA/CM-chitosan/honey hydrogels prepared by using the combined technique of irradiation followed by freeze-thawing,” Radiation Physics and Chemistry, vol. 113, pp. 28–35, Aug. 2015, doi: 10.1016/j.radphyschem.2015.04.023.
[36] A. Shamloo et al., “Fabrication and evaluation of chitosan/gelatin/PVA hydrogel incorporating honey for wound healing applications: An in vitro, in vivo study,” Int J Pharm, vol. 592, p. 120068, Jan. 2021, doi: 10.1016/j.ijpharm.2020.120068.
[37] J.-S. Park, S.-J. An, S.-I. Jeong, H.-J. Gwon, Y.-M. Lim, and Y.-C. Nho, “Chestnut Honey Impregnated Carboxymethyl Cellulose Hydrogel for Diabetic Ulcer Healing,” Polymers (Basel), vol. 9, no. 7, p. 248, Jun. 2017, doi: 10.3390/polym9070248.
[38] S. Noori, M. Kokabi, and Z. M. Hassan, “Poly(vinyl alcohol)/chitosan/honey/clay responsive nanocomposite hydrogel wound dressing,” J Appl Polym Sci, vol. 135, no. 21, p. 46311, Jun. 2018, doi: 10.1002/app.46311.
[39] M. A. Amin and I. T. Abdel-Raheem, “Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats,” Arch Pharm Res, vol. 37, no. 8, pp. 1016–1031, Aug. 2014, doi: 10.1007/s12272-013-0308-y.
[40] Y.-C. Nho, J.-S. Park, and Y.-M. Lim, “Preparation of hydrogel by radiation for the healing of diabetic ulcer,” Radiation Physics and Chemistry, vol. 94, pp. 176–180, Jan. 2014, doi: 10.1016/j.radphyschem.2013.07.021.
[41] Z. Rafati, M. Sirousazar, Z. M. Hassan, and F. Kheiri, “Honey-Loaded Egg White/Poly(vinyl alcohol)/Clay Bionanocomposite Hydrogel Wound Dressings: In Vitro and In Vivo Evaluations,” J Polym Environ, vol. 28, no. 1, pp. 32–46, Jan. 2020, doi: 10.1007/s10924-019-01586-w.
[42] O. O. Erejuwa, S. A. Sulaiman, and M. S. A. Wahab, “Honey - A Novel Antidiabetic Agent,” Int J Biol Sci, vol. 8, no. 6, pp. 913–934, 2012, doi: 10.7150/ijbs.3697.
[43] A. Seckam and R. Cooper, “Understanding how honey impacts on wounds: an update on recent research findings,” Wounds International, vol. 4, no. 1, pp. 20–24, 2013.
[44] Ü. Yapucu Güneş and İ. Eşer, “Effectiveness of a Honey Dressing for Healing Pressure Ulcers,” Journal of Wound, Ostomy & Continence Nursing, vol. 34, no. 2, pp. 184–190, Mar. 2007, doi: 10.1097/01.WON.0000264833.11108.35.
[45] R. Mohd Zohdi, Z. Abu Bakar Zakaria, N. Yusof, N. Mohamed Mustapha, and M. N. H. Abdullah, “Gelam ( Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, pp. 1–7, 2012, doi: 10.1155/2012/843025.
[46] N. Yusof, A. H. Ainul Hafiza, R. M. Zohdi, and M. Z. A. Bakar, “Development of honey hydrogel dressing for enhanced wound healing,” Radiation Physics and Chemistry, vol. 76, no. 11–12, pp. 1767–1770, Nov. 2007, doi: 10.1016/j.radphyschem.2007.02.107.
[47] A. Shukrimi, A. R. Sulaiman, A. Y. Halim, and A. Azril, “A comparative study between honey and povidone iodine as dressing solution for Wagner type II diabetic foot ulcers.,” Med J Malaysia, vol. 63, no. 1, pp. 44–6, Mar. 2008.
[48] U. L. Khatun and C. Mukhopadhyay, “Interaction of bee venom toxin melittin with ganglioside GM1 bicelle,” Biophys Chem, vol. 180–181, pp. 66–75, Oct. 2013, doi: 10.1016/j.bpc.2013.06.012.
[49] R. Silva-Carvalho, F. Baltazar, and C. Almeida-Aguiar, “Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development.,” Evid Based Complement Alternat Med, vol. 2015, p. 206439, 2015, doi: 10.1155/2015/206439.