Leveraging Potential of Nanotherapeutics in Management of Diabetic Foot Ulcer

Abstract

Diabetic foot ulcers (DFUs) are the most common complications associated with diabetes mellitus. DFUs are displayed as open sores or wounds located on the bottom of the foot as a secondary complication of diabetes mellitus (DM). DFUs are associated with significant morbidity and mortality and can subsequently lead to hospitalization and lower limb amputation if not recognized and treated on time. An immense challenge to conventional treatments is caused by the chronic nature of diabetic foot syndrome and it has led to the emergence of nanotechnology-based therapeutics. The greatest advantages of these nanotherapeutics are their unique biological, chemical, and physical properties. The present review highlights the augmentation of bacterial infections relating to delayed healing of DFUs and the potential of nanotherapeutics such as polymeric nanoparticles, metallic nanoparticles, siRNA-based nanoparticles, lipid nanoparticles, and nanofibers in accelerating wound healing in diabetic foot ulcers.

Key words

Nanotechnology - diabetes mellitus - diabetic foot ulcer - wound healing - pathophysiology - nanotherapeutics

Publikationsverlauf

Eingereicht: 14. Oktober 2021
Eingereicht: 10. Januar 2022

Angenommen: 18. Januar 2022

Artikel online veröffentlicht:
03. März 2022

• References

• 1 Ansari MA, Ali K, Farooqui Z. et al. Nanotechnology and Diabetic Foot Ulcer: Future Prospects. In: Zubair M, Ahmad J, Malik A, Talluri MR, eds. Diabetic foot ulcer. Singapore: Springer; 2021.
• 2 Oguntibeju OO. Medicinal plants and their effects on diabetic wound healing. Vet World 2019; 12: 653
• 3 Greaves NS, Ashcroft KJ, Baguneid M. et al. Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci 2013; 72: 206-217
• 4 Moeini M, Shahriari M, Yousefi H. et al. An investigation on the wound severity and its association with predisposing factors in patients with diabetic foot. J Clin Nurs Midwifery 2017; 5: 67-75
• 5 Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci 2018; 1411: 153-165
• 6 Basu S, Yudkin JS, Kehlenbrink S. et al. Estimation of global insulin use for type 2 diabetes, 2018–30: a microsimulation analysis. Lancet Diabetes Endocrinol 2019; 7: 25-33
• 7 Behl T, Grover M, Shah K. et al. Role of Omega-3-Fatty Acids in the Management of Diabetes and Associated Complications. In: Watson RW, Preedy RV, eds. Bioactive food as dietary interventions for diabetes. Academic Press; 2019: 185-192
• 8 Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87: 4-14
• 9 Whiting DR, Guariguata L, Weil C. et al. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94: 311-321
• 10 Yazdanpanah L, Nasiri M, Adarvishi S. Literature review on the management of diabetic foot ulcer. World J Diabetes 2015; 6: 37-53
• 11 Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 2018; 14: 88-98
• 12 Alavi A, Sibbald RG, Mayer D. et al. Diabetic foot ulcers: Part I. Pathophysiology and prevention. J Am Acad Dermatol 2014; 70: 1-e1
• 13 Farahani RM, Kloth LC. The hypothesis of ‘biophysical matrix contraction’: Wound contraction revisited. Int Wound J 2008; 5: 477-482
• 14 Ezhilarasu H, Vishalli D, Dheen ST. et al. Nanoparticle-based therapeutic approach for diabetic wound healing. Nanomaterials 2020; 10: 1234
• 15 Sindhu S. An overview on diabetic foot ulcer (DFU): Mini review. Diabetes Case Rep 2018; 3: 134
• 16 Pouget C, Dunyach-Remy C, Pantel A. et al. Biofilms in diabetic foot ulcers: Significance and clinical relevance. Microorganisms 2020; 8: 1580
• 17 Lavery LA, Bhavan K, Wukich DK. Biofilm and diabetic foot ulcer healing: All hat and no cattle. Ann Transl Med 2019; 7: 159
• 18 Yang S, Hu L, Han R. et al. Neuropeptides, inflammation, biofilms, and diabetic foot ulcers. Exp Clin Endocrinol Diabetes 2021;
• 19 Afonso AC, Oliveira D, Saavedra MJ. et al. Biofilms in diabetic foot ulcers: Impact, risk factors and control strategies. Int J Mol Sci 2021; 22: 8278
• 20 Dowd SE, Wolcott RD, Sun Y. et al. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One 2008; 3: e3326
• 21 Ch’ng JH, Chong KK, Lam LN. et al. Biofilm-associated infection by enterococci. Nat Rev Microbiol 2019; 17: 82-94
• 22 Chellappan DK, Yenese Y, Wei CC. et al. Nanotechnology and diabetic wound healing: A review. Endocr Metab Immune Disord Drug Targets 2017; 17: 87-95
• 23 Santema TB, Poyck PP, Ubbink DT. Systematic review and meta-analysis of skin substitutes in the treatment of diabetic foot ulcers: Highlights of a Cochrane systematic review. Wound Repair Regen 2016; 24: 737-744
• 24 Dixon D, Edmonds M. Managing diabetic foot ulcers: Pharmacotherapy for wound healing. Drugs 2021; 81: 29-56
• 25 Hussain Z, Thu HE, Shuid AN. et al. Recent advances in polymer-based wound dressings for the treatment of diabetic foot ulcer: An overview of state-of-the-art. Curr Drug Targets 2018; 19: 527-550
• 26 Zare H, Rezayi M, Aryan E. et al. Nanotechnology-driven advances in the treatment of diabetic wounds. Biotechnol Appl Biochem 2021; 68: 1281-1306
• 27 Bernal-Chávez S, Nava-Arzaluz MG, Quiroz-Segoviano RI. et al. Nanocarrier-based systems for wound healing. Drug Dev Ind Pharm 2019; 45: 1389-1402
• 28 Vellayappan MV, Jaganathan SK, Manikandan A. Nanomaterials as a game changer in the management and treatment of diabetic foot ulcers. RSC Adv 2016; 6: 114859-114878
• 29 Asadi N, Pazoki-Toroudi H, Del Bakhshayesh AR. et al. Multifunctional hydrogels for wound healing: Special focus on biomacromolecular based hydrogels. Int J Biol Macromol 2021; 170: 728-750
• 30 Bairagi U, Mittal P, Singh J. et al. Preparation, characterization, and in vivo evaluation of nano formulations of ferulic acid in diabetic wound healing. Drug Dev Ind Pharm 2018; 44: 1783-1796
• 31 Almonaci Hernández CA, Juarez-Moreno K, Castañeda-Juarez ME. et al. Silver nanoparticles for the rapid healing of diabetic foot ulcers. Int J Med Nano Res 2017; 4: 019
• 32 Tsang KK, Kwong EW, To TS. et al. A pilot randomized, controlled study of nanocrystalline silver, manuka honey, and conventional dressing in healing diabetic foot ulcer. Evid Based Complement Alternat Med: Ecam 2017; 2017: 5294890
• 33 Singla R, Soni S, Kulurkar PM. et al. In situ functionalized nanobiocomposites dressings of bamboo cellulose nanocrystals and silver nanoparticles for accelerated wound healing. Carbohydr Polym 2017; 155: 152-162
• 34 Almonaci Hernández CA, Juarez-Moreno K, Castañeda-Juarez ME. et al. Silver nanoparticles for the rapid healing of diabetic foot ulcers. Int. J. Med. Nano Res 2017; 4: 2378-3664
• 35 Appapalam ST, Paul B, Arockiasamy S. et al. Phytofabricated silver nanoparticles: Discovery of antibacterial targets against diabetic foot ulcer derived resistant bacterial isolates. Mater Sci Eng C 2020; 117: 111256
• 36 Li XX, Dong JY, Li YH. et al. Fabrication of Ag–ZnO@ carboxymethyl cellulose/K-carrageenan/graphene oxide/konjac glucomannan hydrogel for effective wound dressing in nursing care for diabetic foot ulcers. Appl Nanosci 2020; 10: 729-738
• 37 Yu J, Wang X, Li Y. et al. Synthesis of nerolidol functionalized gold nanoparticles for wound regeneration in people with diabetic foot ulcers in nursing care management. Sci Adv Mater 2018; 10: 1775-1781
• 38 Hernández Martínez SP, Rivera González TI Franco. et al. A novel gold calreticulin nanocomposite based on chitosan for wound healing in a diabetic mice model. Nanomaterials 2019; 9: 75
• 39 López-Goerne T, Ramírez-Olivares P, Pérez-Dávalos LA. et al. Catalytic nanomedicine. Cu/TiO2–SiO2 nanoparticles as treatment of diabetic foot ulcer: a case report. Curr Nanomed 2020; 10: 290-295
• 40 Goerne TL, Arévalo A, Ramírez P. et al. Copper nanoparticles as treatment of diabetic foot ulcers: A case report. Glob Adv Res J Med Med Sci 2017; 6: 267-270
• 41 Xiao J, Zhu Y, Huddleston S. et al. Copper metal–organic framework nanoparticles stabilized with folic acid improve wound healing in diabetes. ACS Nano 2018; 12: 1023-1032
• 42 Gupta S, Bansal R, Gupta S. et al. Nanocarriers and nanoparticles for skin care and dermatological treatments. Indian Dermatol Online J 2013; 4: 267-272
• 43 Steffy K, Shanthi G, Maroky AS. et al. Enhanced antibacterial effects of green synthesized ZnO NPs using Aristolochia indica against Multi-drug resistant bacterial pathogens from Diabetic Foot Ulcer. J Infect Public Health 2018; 11: 463-471
• 44 Liu D, Liu L, Yao L. et al. Synthesis of ZnO nanoparticles using radish root extract for effective wound dressing agents for diabetic foot ulcers in nursing care. J Drug Deliv Sci Technol 2020; 55: 101364
• 45 Zgheib C, Hilton SA, Dewberry LC. et al. Use of cerium oxide nanoparticles conjugated with microRNA-146a to correct the diabetic wound healing impairment. J Am Coll Surg 2019; 228: 107-115
• 46 Kobyliak N, Abenavoli L, Kononenko L. et al. Neuropathic diabetic foot ulcers treated with cerium dioxide nanoparticles: A case report. Diabetes Metab Syndr 2019; 13: 228-234
• 47 Yan LP, Castaño IM, Sridharan R. et al. Collagen/GAG scaffolds activated by RALA-siMMP-9 complexes with potential for improved diabetic foot ulcer healing. Mater Sci Eng C 2020; 114: 111022
• 48 Kim HS, Yoo HS. In vitro and in vivo epidermal growth factor gene therapy for diabetic ulcers with electrospun fibrous meshes. Acta Biomaterialia 2013; 9: 7371-7380
• 49 De Souza ML, Dos Santos WM, de Sousa ALMD. et al. Lipid nanoparticles as a skin wound healing drug delivery system: discoveries and advances. Curr Pharm Des 2020; 26: 4536-4550
• 50 Natarajan J, Sanapalli BKR, Bano M. Nanostructured lipid carriers of pioglitazone loaded collagen/chitosan composite scaffold for diabetic wound healing. Adv Wound Caref 2019; 8: 499-513
• 51 Motawea A, Abd El-Gawad AEH, Borg T. et al. The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration. Foot (Edinb) 2019; 40: 14-21
• 52 Sun D, Guo SY, Yang L. et al. Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery. Acta Pharmacol Sin 2020; 41: 119-128
• 53 Goonoo N, Bhaw-Luximon A. Analyzing polymeric nanofibrous scaffold performances in diabetic animal models for translational chronic wound healing research. Nanotechnol Rev 2017; 6: 583-600
• 54 Ruggeri M, Bianchi E, Rossi S. et al. Nanotechnology-based medical devices for the treatment of chronic skin lesions: from research to the clinic. Pharmaceutics 2020; 12: 815
• 55 Assi R, Foster TR, He H. et al. Delivery of mesenchymal stem cells in biomimetic engineered scaffolds promotes healing of diabetic ulcers. Regen Med 2016; 11: 245-260
• 56 Zheng Z, Liu Y, Huang W. et al. Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing. Artif Cells Nanomed Biotechnol 2018; 46: 493-501
• 57 Liu Y, Zhou S, Gao Y. et al. Electrospun nanofibers as a wound dressing for treating diabetic foot ulcer. Asian J Pharm Sci 2019; 14: 130-143
• 58 Samadian H, Zamiri S, Ehterami A. et al. Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: In vitro and in vivo studies. Sci Rep 2020; 10: 1-2
• 59 Li Y, Xu T, Tu Z. et al. Bioactive antibacterial silica-based nanocomposites hydrogel scaffolds with high angiogenesis for promoting diabetic wound healing and skin repair. Theranostics 2020; 10: 4929
• 60 Roy S, Bisaria K, Nagabooshanam S. et al. An electroanalytical paper-based wound dressing using ZIF-67/C 3 N 4 nanocomposite towards the monitoring of staphylococcus aureus in diabetic foot ulcer. IEEE Sens J 2020; 21: 1215-1221
• 61 Ouyang J. et al. In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer treatment. Proc Natl Acad Sci U S A 2020; 117: 28667-28677
• 62 Layliev J, Wilson S, Warren SM. et al. Improving wound healing with topical gene therapy. Adv Wound Care 2012; 1: 218-223
• 63 Naderi N, Karponis D, Mosahebi A. et al. Nanoparticles in wound healing; from hope to promise, from promise to routine. Front Biosci 2018; 23: 1038-1059
• 64 Gunatillake PA, Adhikari R. Biodegradable synthetic polymers for tissue engineering. Eur Cell Mater 2003; 5: 1-16
• 65 Li W, Tsen F, Sahu D. et al. Extracellular Hsp90 (eHsp90) as the actual target in clinical trials: Intentionally or unintentionally. Int Rev Cell Mol Biol 2013; 303: 203-235
• 66 Nethi SK, Das S, Patra CR. et al. Recent advances in inorganic nanomaterials for wound-healing applications. Biomater Sci 2019; 7: 2652-2674
• 67 Hamdan S, Pastar I, Drakulich S. et al. Nanotechnology-driven therapeutic interventions in wound healing: Potential uses and applications. ACS Cent Sci 2017; 3: 163-175