Nano Drug Delivery System with Resveratrol as Promising Novel Adjuvant Therapy for Diabetic Non-Healing Wounds: A Literature Review

https://doi.org/10.22146/jmpf.84181

Ni Wayan Puspita Sari(1), Vanessa Els(2), Agung Wiwiek Indrayani(3*)

(1) Department of Pharmacology and Therapeutic, Faculty of Medicine, Udayana University
(2) Department of Pharmacology and Therapeutic, Faculty of Medicine, Udayana University
(3) Department of Pharmacology and Therapeutic, Faculty of Medicine, Udayana University
(*) Corresponding Author

Abstract


Diabetes mellitus (DM) is a metabolic disease characterized by increased blood sugar levels (hyperglycemia) and is associated with impaired function of β cells. The uncontrolled and prolonged hyperglycemia in DM can cause complications. One of the most common is diabetic non-healing wounds, the leading cause of disability in people with diabetes, therefore adjuvant therapy is needed. Compounds from natural ingredients are currently getting the spotlight in recent studies conducted to prove their effect on non-healing wounds, such as Resveratrol (RSV). This review aims to discuss the potential of RSV as a novel adjuvant therapy and its delivery system strategy in the case of diabetic non-healing wounds. We conducted an extensive search from three online scientific databases such as ScienceDirect, ResearchGate, and PubMed on February-March 2023. Keywords used are "resveratrol", "diabetic wound healing", and "diabetes mellitus". As a result, 86 studies were reviewed, and only 79 selected studies met all inclusion criteria. The formulation of RSV nanoparticles in oral drug delivery systems and topical administration has shown promise to overcome the limitations of RSV as adjuvant therapy in diabetic non-healing wounds. The best option that we found through this literature review is the nano-oral drug delivery system as it could minimize drug metabolism in the gastrointestinal tract, therefore the drug bioavailability and drug concentration on the target site could be maximized, even though the systemic side effects might occur.

Keywords


Nano-resveratrol; Type 2 Diabetes Mellitus; Diabetic Non-Healing Wounds

Full Text:

PDF


References

  1. Christensen AA, Gannon M. The Beta Cell in Type 2 Diabetes. Curr Diab Rep. 2019;19(9). doi:10.1007/S11892-019-1196-4
  2. Roep BO, Thomaidou S, van Tienhoven R, Zaldumbide A. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?). Nat Rev Endocrinol. 2021;17(3):150-161. doi:10.1038/S41574-020-00443-4
  3. Moin ASM, Butler AE. Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes. Curr Diab Rep. 2019;19(9). doi:10.1007/S11892-019-1194-6
  4. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †. Ann Med. 2017;49(2):106-116. doi:10.1080/07853890.2016.1231932
  5. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183. doi:10.1016/J.DIABRES.2021.109119
  6. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol. 2019;11(3):45. Accessed March 26, 2023. /pmc/articles/PMC6628012/
  7. Deng L, Du C, Song P, et al. The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing. Oxid Med Cell Longev. 2021;2021. doi:10.1155/2021/8852759
  8. Reardon R, Simring D, Kim B, Mortensen J, Williams D, Leslie A. The diabetic foot ulcer. Aust J Gen Pract. 2020;49(5):250-255. doi:10.31128/AJGP-11-19-5161
  9. Zhang W, Chen L, Xiong Y, et al. Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing. Front Bioeng Biotechnol. 2021;9. doi:10.3389/FBIOE.2021.707479
  10. Gu T, Wang N, Wu T, Ge Q, Chen L. Antioxidative Stress Mechanisms behind Resveratrol: A Multidimensional Analysis. J Food Qual. 2021;2021. doi:10.1155/2021/5571733
  11. Song J, Liu A, Liu B, et al. Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress. Frontiers in Bioscience - Landmark. 2022;27(10):285. doi:10.31083/J.FBL2710285/2768-6698-27-10-285/FIG1.JPG
  12. Han HS, Koo SY, Choi KY. Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging. Bioact Mater. 2022;14:182-205. doi:10.1016/J.BIOACTMAT.2021.11.027
  13. Natesan V, Kim SJ. The Trend of Organic Based Nanoparticles in the Treatment of Diabetes and Its Perspectives. Biomol Ther (Seoul). 2023;31(1):16. doi:10.4062/BIOMOLTHER.2022.080
  14. Colica C, Milanović M, Milić N, Aiello V, De Lorenzo A, Abenavoli L. A systematic review on natural antioxidant properties of resveratrol. Nat Prod Commun. 2018;13(9):1195-1203. doi:10.1177/1934578X1801300923
  15. Meng T, Xiao D, Muhammed A, Deng J, Chen L, He J. Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules. 2021;26(1). doi:10.3390/MOLECULES26010229
  16. Jhaveri A, Deshpande P, Pattni B, Torchilin V. Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma. Journal of Controlled Release. 2018;277:89-101. doi:10.1016/J.JCONREL.2018.03.006
  17. Okamoto-Shibayama K, Yoshida A, Ishihara K. Inhibitory Effect of Resveratrol on Candida albicans Biofilm Formation. Bull Tokyo Dent Coll. 2021;62(1):1-6. doi:10.2209/TDCPUBLICATION.2020-0023
  18. Gambini J, Inglés M, Olaso G, et al. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans. Oxid Med Cell Longev. 2015;2015. doi:10.1155/2015/837042
  19. Weiskirchen S, Weiskirchen R. Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy? Adv Nutr. 2016;7(4):706-718. doi:10.3945/AN.115.011627
  20. Meng X, Zhou J, Zhao CN, Gan RY, Li H Bin. Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review. Foods. 2020;9(3). doi:10.3390/FOODS9030340
  21. Truong VL, Jun M, Jeong WS. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors. 2018;44(1):36-49. doi:10.1002/BIOF.1399
  22. Fiod Riccio BV, Fonseca-Santos B, Colerato Ferrari P, Chorilli M. Characteristics, Biological Properties and Analytical Methods of Trans-Resveratrol: A Review. Crit Rev Anal Chem. 2020;50(4):339-358. doi:10.1080/10408347.2019.1637242
  23. Izzo C, Annunziata M, Melara G, et al. The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials. Nutrients. 2021;13(3):1-23. doi:10.3390/NU13030933
  24. Park SJ, Ahmad F, Philp A, et al. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases. Cell. 2012;148(3):421. doi:10.1016/J.CELL.2012.01.017
  25. Netea MG, Balkwill F, Chonchol M, et al. A guiding map for inflammation. Nat Immunol. 2017;18(8):826-831. doi:10.1038/NI.3790
  26. Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-1832. doi:10.1038/S41591-019-0675-0
  27. Fuggetta MP, Bordignon V, Cottarelli A, et al. Downregulation of proinflammatory cytokines in HTLV-1-infected T cells by Resveratrol. J Exp Clin Cancer Res. 2016;35(1). doi:10.1186/S13046-016-0398-8
  28. Devi P, Sharma P, Rathore C, Negi P. Novel Drug Delivery Systems of Resveratrol to Bioavailability and Therapeutic Effects. Resveratrol - Adding Life to Years, Not Adding Years to Life. Published online February 6, 2019. doi:10.5772/INTECHOPEN.79739
  29. Ratz-Łyko A, Arct J. Resveratrol as an active ingredient for cosmetic and dermatological applications: a review. J Cosmet Laser Ther. 2019;21(2):84-90. doi:10.1080/14764172.2018.1469767
  30. Shabani M, Sadeghi A, Hosseini H, et al. Resveratrol alleviates obesity-induced skeletal muscle inflammation via decreasing M1 macrophage polarization and increasing the regulatory T cell population. Sci Rep. 2020;10(1). doi:10.1038/S41598-020-60185-1
  31. Ren Z, Wang L, Cui J, et al. Resveratrol inhibits NF-κB signaling through suppression of p65 and I B kinase activities. Pharmazie. 2013;68(8):689-694. doi:10.1691/PH.2013.2916
  32. Davis FM, Kimball A, Boniakowski A, Gallagher K. Dysfunctional Wound Healing in Diabetic Foot Ulcers: New Crossroads. Curr Diab Rep. 2018;18(1). doi:10.1007/S11892-018-0970-Z
  33. Trøstrup H, Bjarnsholt T, Kirketerp-Møller K, Høiby N, Moser C. What Is New in the Understanding of Non Healing Wounds Epidemiology, Pathophysiology, and Therapies. Ulcers. 2013;2013:1-8. doi:10.1155/2013/625934
  34. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and Treatment of Impaired Wound Healing in Diabetes Mellitus: New Insights. Adv Ther. 2014;31(8):817-836. doi:10.1007/S12325-014-0140-X/METRICS
  35. Boulton AJM. The pathway to foot ulceration in diabetes. Med Clin North Am. 2013;97(5):775-790. doi:10.1016/J.MCNA.2013.03.007
  36. Dwivedi C, Pandey I, Pandey H, et al. Electrospun Nanofibrous Scaffold as a Potential Carrier of Antimicrobial Therapeutics for Diabetic Wound Healing and Tissue Regeneration. Nano- and Microscale Drug Delivery Systems: Design and Fabrication. Published online March 29, 2017:147-164. doi:10.1016/B978-0-323-52727-9.00009-1
  37. Pradhan Nabzdyk L, Kuchibhotla S, Guthrie P, et al. Expression of neuropeptides and cytokines in a rabbit model of diabetic neuroischemic wound healing. J Vasc Surg. 2013;58(3). doi:10.1016/J.JVS.2012.11.095
  38. Tellechea A, Kafanas A, Leal EC, et al. Increased skin inflammation and blood vessel density in human and experimental diabetes. Int J Low Extrem Wounds. 2013;12(1):4-11. doi:10.1177/1534734612474303
  39. Declue CE, Shornick LP. The cytokine milieu of diabetic wounds. 2015;5(6):525-537. doi:10.2217/dmt.15.44
  40. Xu F, Zhang C, Graves DT. Abnormal Cell Responses and Role of TNF-α in Impaired Diabetic Wound Healing. Biomed Res Int. 2013;2013. doi:10.1155/2013/754802
  41. Sloan-Lancaster J, Abu-Raddad E, Polzer J, et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β antibody, in patients with type 2 diabetes. Diabetes Care. 2013;36(8):2239-2246. doi:10.2337/DC12-1835
  42. Martins VL, Caley M, O’Toole EA. Matrix metalloproteinases and epidermal wound repair. Cell Tissue Res. 2013;351(2):255-268. doi:10.1007/S00441-012-1410-Z
  43. Tecilazich F, Dinh TL, Veves A. Emerging drugs for the treatment of diabetic ulcers. Expert Opin Emerg Drugs. 2013;18(2):207-217. doi:10.1517/14728214.2013.802305
  44. Britton RG, Kovoor C, Brown K. Direct molecular targets of resveratrol: identifying key interactions to unlock complex mechanisms. Ann N Y Acad Sci. 2015;1348(1):124-133. doi:10.1111/NYAS.12796
  45. Smoliga JM, Blanchard O. Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution? Molecules. 2014;19(11):17154-17172. doi:10.3390/MOLECULES191117154
  46. Murakami I, Chaleckis R, Pluskal T, et al. Metabolism of Skin-Absorbed Resveratrol into Its Glucuronized Form in Mouse Skin. PLoS One. 2014;9(12):e115359. doi:10.1371/JOURNAL.PONE.0115359
  47. García-Martínez BI, Ruiz-Ramos M, Pedraza-Chaverri J, Santiago-Osorio E, Mendoza-Núñez VM. Hypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis. Antioxidants 2021, Vol 10, Page 69. 2021;10(1):69. doi:10.3390/ANTIOX10010069
  48. Su M, Zhao W, Xu S, Weng J. Resveratrol in Treating Diabetes and Its Cardiovascular Complications: A Review of Its Mechanisms of Action. Antioxidants 2022, Vol 11, Page 1085. 2022;11(6):1085. doi:10.3390/ANTIOX11061085
  49. Mohseni R, ArabSadeghabadi Z, Ziamajidi N, Abbasalipourkabir R, RezaeiFarimani A. Oral Administration of Resveratrol-Loaded Solid Lipid Nanoparticle Improves Insulin Resistance Through Targeting Expression of SNARE Proteins in Adipose and Muscle Tissue in Rats with Type 2 Diabetes. Nanoscale Res Lett. 2019;14(1). doi:10.1186/S11671-019-3042-7
  50. Balata GF, Essa EA, Shamardl HA, Zaidan SH, Abourehab MAS. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol. Drug Des Devel Ther. 2016;10:117-128. doi:10.2147/DDDT.S95905
  51. Bruckbauer A, Zemel MB. Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity. Diabetes Metab Syndr Obes. 2013;6:93-102. doi:10.2147/DMSO.S40840
  52. Tamimi LN, Zakaraya Z, Hailat M, et al. Anti-diabetic effect of cotreatment with resveratrol and pioglitazone in diabetic rats. Eur Rev Med Pharmacol Sci. 2023;27(1):325-332. doi:10.26355/EURREV_202301_30879
  53. Su J, Li J, Liang J, Zhang K, Li J. Hydrogel Preparation Methods and Biomaterials for Wound Dressing. Life. 2021;11(10). doi:10.3390/LIFE11101016
  54. Ousey K, Cutting KF, Rogers AA, Rippon MG. The importance of hydration in wound healing: reinvigorating the clinical perspective. J Wound Care. 2016;25(3):122-130. doi:10.12968/JOWC.2016.25.3.122
  55. Nuutila K, Eriksson E. Moist Wound Healing with Commonly Available Dressings. Adv Wound Care (New Rochelle). 2021;10(12):685-698. doi:10.1089/WOUND.2020.1232
  56. Koehler J, Brandl FP, Goepferich AM. Hydrogel wound dressings for bioactive treatment of acute and chronic wounds. Eur Polym J. 2018;100:1-11. doi:10.1016/J.EURPOLYMJ.2017.12.046
  57. Górska A, Krupa A, Majda D, et al. Poly(Vinyl Alcohol) Cryogel Membranes Loaded with Resveratrol as Potential Active Wound Dressings. AAPS PharmSciTech. 2021;22(3). doi:10.1208/S12249-021-01976-1
  58. Gokce EH, Tuncay Tanrıverdi S, Eroglu I, et al. Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats. Eur J Pharm Biopharm. 2017;119:17-27. doi:10.1016/J.EJPB.2017.04.027
  59. Zhu W, Dong Y, Xu P, et al. A composite hydrogel containing resveratrol-laden nanoparticles and platelet-derived extracellular vesicles promotes wound healing in diabetic mice. Acta Biomater. 2022;154:212-230. doi:10.1016/J.ACTBIO.2022.10.038
  60. Moeini A, Pedram P, Makvandi P, Malinconico M, Gomez d’Ayala G. Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: A review. Carbohydr Polym. 2020;233. doi:10.1016/j.carbpol.2020.115839
  61. Kulkarni SS, Cantó C. The molecular targets of resveratrol. Biochim Biophys Acta. 2015;1852(6):1114-1123. doi:10.1016/J.BBADIS.2014.10.005
  62. Singh AP, Singh R, Verma SS, et al. Health benefits of resveratrol: Evidence from clinical studies. Med Res Rev. 2019;39(5):1851-1891. doi:10.1002/MED.21565
  63. Pignet AL, Schellnegger M, Hecker A, Kohlhauser M, Kotzbeck P, Kamolz LP. Resveratrol-Induced Signal Transduction in Wound Healing. International Journal of Molecular Sciences 2021, Vol 22, Page 12614. 2021;22(23):12614. doi:10.3390/IJMS222312614
  64. Varoni EM, Lo Faro AF, Sharifi-Rad J, Iriti M. Anticancer Molecular Mechanisms of Resveratrol. Front Nutr. 2016;3. doi:10.3389/FNUT.2016.00008
  65. Das A, Huang GX, Bonkowski MS, et al. Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging. Cell. 2018;173(1):74-89.e20. doi:10.1016/J.CELL.2018.02.008
  66. Huang X, Sun J, Chen G, et al. Resveratrol promotes diabetic wound healing via SIRT1-FoxO1-c-Myc signaling pathway-mediated angiogenesis. Front Pharmacol. 2019;10(APR):421. doi:10.3389/FPHAR.2019.00421/BIBTEX
  67. Wilhelm K, Happel K, Eelen G, et al. FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature 2016 529:7585. 2016;529(7585):216-220. doi:10.1038/nature16498
  68. Zhao P, Sui BD, Liu N, et al. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application. Aging Cell. 2017;16(5):1083-1093. doi:10.1111/ACEL.12635
  69. Çetinkalp Ş, Gökçe EH, Şimşir IY, et al. Comparative Evaluation of Clinical Efficacy and Safety of Collagen Laminin–Based Dermal Matrix Combined With Resveratrol Microparticles (Dermalix) and Standard Wound Care for Diabetic Foot Ulcers. https://doi.org/101177/1534734620907773. 2020;20(3):217-226. doi:10.1177/1534734620907773
  70. Ayuk SM, Abrahamse H, Houreld NN. The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation. J Diabetes Res. 2016;2016. doi:10.1155/2016/2897656
  71. Deng L, Du C, Song P, et al. The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing. Oxid Med Cell Longev. 2021;2021. doi:10.1155/2021/8852759
  72. Mahmoudvand G, Karimi Rouzbahani A, Razavi ZS, Mahjoor M, Afkhami H. Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight. Front Bioeng Biotechnol. 2023;11. doi:10.3389/FBIOE.2023.1158484
  73. Movahed A, Nabipour I, Lieben Louis X, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013. doi:10.1155/2013/851267
  74. Mahjabeen W, Khan DA, Mirza SA. Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial. Complement Ther Med. 2022;66. doi:10.1016/J.CTIM.2022.102819
  75. Bashmakov YK, Assaad-Khalil SH, Abou Seif M, et al. Resveratrol promotes foot ulcer size reduction in type 2 diabetes patients. ISRN Endocrinol. 2014;2014:1-8. doi:10.1155/2014/816307
  76. Alasmari W, ElSawy NA, Abourehab, M. A., Faruk, E. M., & Alasmari, A. A. Effect of topical resveratrol formulation on healing of experimental full thickness wound in diabetic male albino rats: (histological and immunohistochemical study). Life Sci. 2018;15(10):6-20. doi:10.7537/marslsj151018.02.Keywords
  77. Zhou X, Ruan Q, Ye Z, et al. Resveratrol accelerates wound healing by attenuating oxidative stress-induced impairment of cell proliferation and migration. Burns. 2021;47(1):133-139. doi:10.1016/J.BURNS.2020.10.016
  78. Ma N, Zhang Y. Effects of resveratrol therapy on glucose metabolism, insulin resistance, inflammation, and renal function in the elderly patients with type 2 diabetes mellitus: A randomized controlled clinical trial protocol. Medicine. 2022;101(32):E30049. doi:10.1097/MD.0000000000030049
  79. Khodabandehloo H, Seyyedebrahimi SS, Esfahani EN, Razi F, Meshkani R. Resveratrol supplementation decreases blood glucose without changing the circulating CD14 + CD16 + monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Nutr Res. 2018;54:40-51. doi:10.1016/j.nutres.2018.03.015



DOI: https://doi.org/10.22146/jmpf.84181

Article Metrics

Abstract views : 7951 | views : 7642

Refbacks

  • There are currently no refbacks.


Copyright (c) 2023 JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice)

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Jurnal Manajemen dan Pelayanan Farmasi
Faculty of Pharmacy
Universitas Gadjah Mada
Creative Commons License
View My Stats