Nano Drug Delivery System with Resveratrol as Promising Novel Adjuvant Therapy for Diabetic Non-Healing Wounds: A Literature Review
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:
PDFReferences
- Christensen AA, Gannon M. The Beta Cell in Type 2 Diabetes. Curr Diab Rep. 2019;19(9). doi:10.1007/S11892-019-1196-4
- 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
- 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
- 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
- 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
- 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/
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Declue CE, Shornick LP. The cytokine milieu of diabetic wounds. 2015;5(6):525-537. doi:10.2217/dmt.15.44
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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 : 8117 | views : 7807Refbacks
- There are currently no refbacks.
Copyright (c) 2023 JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.