Skip to content
2000
image of Innovative Nanocomposites for Drug Delivery: A Novel Approach for Diabetic Foot Ulcer

Abstract

Diabetic Foot Ulcer (DFU) is a chronic wound, and a person with diabetes has an increased lifetime risk of foot ulcers (19%-34%) and high morbidity (65% recurrence in 3-5 years, 20% lifetime amputation). Recent data have shown rising amputation rates, especially in the younger and minority populations. This abstract discusses innovative approaches for addressing this issue. This highlights the use of nanotechnology-based drug nanocomposite systems for natural wound healing therapies, with a focus on nanoparticles, nano-emulsions, and nanogels. This review also emphasizes the potential of hydrogels for drug delivery, highlighting their versatility in various medical applications. Furthermore, it delves into the use of silver nanoparticles (AgNP’s) for treating diabetic wounds while acknowledging the need to address potential toxicity concerns. Finally, the abstract discusses the utilization of traditional herbal medicine and the integration of modern science to advance wound care, particularly focusing on wound microbiome, immune response, and controlled herbal medicine delivery. This study also highlights clinical trials conducted on DFU. Overall, these abstracts highlight the importance of exploring diverse and innovative solutions to chronic wound management.

Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018322140241023054041
2024-11-07
2025-01-22
Loading full text...

Full text loading...

References

  1. Artasensi A. Pedretti A. Vistoli G. Fumagalli L. Type 2 diabetes mellitus: A review of multi-target drugs. Molecules 2020 25 8 1987 10.3390/molecules25081987 32340373
    [Google Scholar]
  2. Cole J.B. Florez J.C. Genetics of diabetes mellitus and diabetes complications. Nat. Rev. Nephrol. 2020 16 7 377 390 10.1038/s41581‑020‑0278‑5 32398868
    [Google Scholar]
  3. Berlanga-Acosta J. Fernández-Montequín J. Valdés-Pérez C. Savigne-Gutiérrez W. Mendoza-Marí Y. García-Ojalvo A. Falcón-Cama V. García del Barco-Herrera D. Fernández-Mayola M. Pérez-Saad H. Pimentel-Vázquez E. Urquiza-Rodríguez A. Kulikovsky M. Guillén-Nieto G. Diabetic foot ulcers and epidermal growth factor: Revisiting the local delivery route for a successful outcome. BioMed Res. Int. 2017 2017 1 1 10 10.1155/2017/2923759 28904951
    [Google Scholar]
  4. McDermott K. Fang M. Boulton A.J.M. Selvin E. Hicks C.W. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care 2023 46 1 209 221 10.2337/dci22‑0043 36548709
    [Google Scholar]
  5. Noor S. Zubair M. Ahmad J. Diabetic foot ulcer—A review on pathophysiology, classification and microbial etiology. Diabetes Metab. Syndr. 2015 9 3 192 199 10.1016/j.dsx.2015.04.007 25982677
    [Google Scholar]
  6. Everett E. Mathioudakis N. Update on management of diabetic foot ulcers. Ann. N. Y. Acad. Sci. 2018 1411 1 153 165 10.1111/nyas.13569 29377202
    [Google Scholar]
  7. Kavitha K.V. Tiwari S. Purandare V.B. Khedkar S. Bhosale S.S. Unnikrishnan A.G. Choice of wound care in diabetic foot ulcer: A practical approach. World J. Diabetes 2014 5 4 546 556 10.4239/wjd.v5.i4.546 25126400
    [Google Scholar]
  8. Aldana P.C. Khachemoune A. Diabetic foot ulcers: Appraising standard of care and reviewing new trends in management. Am. J. Clin. Dermatol. 2020 21 2 255 264 10.1007/s40257‑019‑00495‑x 31848923
    [Google Scholar]
  9. Doğruel H. Aydemir M. Balci M.K. Management of diabetic foot ulcers and the challenging points: An endocrine view. World J. Diabetes 2022 13 1 27 36 10.4239/wjd.v13.i1.27 35070057
    [Google Scholar]
  10. Naves C.C.L.M. The diabetic foot: A historical overview and gaps in current treatment. Adv. Wound Care (New Rochelle) 2016 5 5 191 197 10.1089/wound.2013.0518 27134763
    [Google Scholar]
  11. Abbas M. Saeed F. Anjum F.M. Afzaal M. Tufail T. Bashir M.S. Ishtiaq A. Hussain S. Suleria H.A.R. Natural polyphenols: An overview. Int. J. Food Prop. 2017 20 8 1689 1699 10.1080/10942912.2016.1220393
    [Google Scholar]
  12. Khursheed R. Singh S.K. Wadhwa S. Gulati M. Kapoor B. Awasthi A. Kr A. Kumar R. Pottoo F.H. Kumar V. Dureja H. Anand K. Chellappan D.K. Dua K. Gowthamarajan K. Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications. Expert Opin. Drug Deliv. 2021 18 4 427 448 10.1080/17425247.2021.1846517 33356647
    [Google Scholar]
  13. Jones O.G. McClements D.J. Recent progress in biopolymer nanoparticle and microparticle formation by heat-treating electrostatic protein–polysaccharide complexes. Adv. Colloid Interface Sci. 2011 167 1-2 49 62 10.1016/j.cis.2010.10.006 21094486
    [Google Scholar]
  14. Veneranda M. Hu Q. Wang T. Luo Y. Castro K. Madariaga J.M. Formation and characterization of zein-caseinate-pectin complex nanoparticles for encapsulation of eugenol. Lebensm. Wiss. Technol. 2018 89 596 603 10.1016/j.lwt.2017.11.040
    [Google Scholar]
  15. Milinčić D.D. Popović D.A. Lević S.M. Kostić A.Ž. Tešić Ž.L. Nedović V.A. Pešić M.B. Application of polyphenol-loaded nanoparticles in food industry. Nanomaterials (Basel) 2019 9 11 1629 10.3390/nano9111629 31744091
    [Google Scholar]
  16. Deng H. Li B. Shen Q. Zhang C. Kuang L. Chen R. Wang S. Ma Z. Li G. Mechanisms of diabetic foot ulceration: A review. J. Diabetes 2023 15 4 299 312 10.1111/1753‑0407.13372 36891783
    [Google Scholar]
  17. Raja J.M. Maturana M.A. Kayali S. Khouzam A. Efeovbokhan N. Diabetic foot ulcer: A comprehensive review of pathophysiology and management modalities. World J. Clin. Cases 2023 11 8 1684 1693 10.12998/wjcc.v11.i8.1684 36970004
    [Google Scholar]
  18. Syafril S. Pathophysiology diabetic foot ulcer. OP Conf. Ser.: Earth Environ. Sci. 2018 125 012161 10.1088/1755‑1315/125/1/012161
    [Google Scholar]
  19. Pouget C. Dunyach-Remy C. Pantel A. Schuldiner S. Sotto A. Lavigne J.P. Biofilms in diabetic foot ulcers: Significance and clinical relevance. Microorganisms 2020 8 10 1580 10.3390/microorganisms8101580 33066595
    [Google Scholar]
  20. Ali R. Shahid A. Ali N. Hasan S.K. Majed F. Sultana S. Amelioration of Benzo[a]pyrene-induced oxidative stress and pulmonary toxicity by Naringenin in Wistar rats: A plausible role of COX-2 and NF-κB. Hum. Exp. Toxicol. 2017 36 4 349 364 10.1177/0960327116650009 27206700
    [Google Scholar]
  21. Guimarães I. Baptista-Silva S. Pintado M. Polyphenols: A promising avenue in therapeutic solutions for wound care. Appl. Sci. (Basel) 2021 11 3 1230 10.3390/app11031230
    [Google Scholar]
  22. Singla R.K. Dubey A.K. Garg A. Sharma R.K. Fiorino M. Ameen S.M. Haddad M.A. Al-Hiary M. Natural polyphenols: Chemical classification, definition of classes, subcategories, and structures. J. AOAC Int. 2019 102 5 1397 1400 10.5740/jaoacint.19‑0133 31200785
    [Google Scholar]
  23. Maleki Dana P. Sadoughi F. Mansournia M.A. Mirzaei H. Asemi Z. Yousefi B. Targeting Wnt signaling pathway by polyphenols: Implication for aging and age-related diseases. Biogerontology 2021 22 5 479 494 10.1007/s10522‑021‑09934‑x 34480268
    [Google Scholar]
  24. Jin T. Curcumin and dietary polyphenol research: Beyond drug discovery. Acta Pharmacol. Sin. 2018 39 5 779 786 10.1038/aps.2017.179 29542686
    [Google Scholar]
  25. Amawi H. Ashby C. Jr Samuel T. Peraman R. Tiwari A. Polyphenolic nutrients in cancer chemoprevention and metastasis: Role of the epithelial-to-mesenchymal (EMT) pathway. Nutrients 2017 9 8 911 10.3390/nu9080911 28825675
    [Google Scholar]
  26. Egbuna C. Dable-Tupas G. Functional foods and nutraceuticals. Switzerland AG Springer Nature 2020 1 1 632
    [Google Scholar]
  27. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010 2 12 1231 1246 10.3390/nu2121231 22254006
    [Google Scholar]
  28. Silva L.C.R.C. David J.M. Borges R.S.Q. Ferreira S.L.C. David J.P. Reis P.S. Bruns R.E. Determination of flavanones in orange juices obtained from different sources by HPLC/DAD. J. Anal. Methods Chem. 2014 2014 1 1 5 10.1155/2014/296838 25180132
    [Google Scholar]
  29. Adetunji J.A. Fasae K.D. Awe A.I. Paimo O.K. Adegoke A.M. Akintunde J.K. Sekhoacha M.P. The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases. Heliyon 2023 9 6 e17166 10.1016/j.heliyon.2023.e17166 37484296
    [Google Scholar]
  30. Akrawi S.H. Gorain B. Nair A.B. Choudhury H. Pandey M. Shah J.N. Venugopala K.N. Development and optimization of naringenin-loaded chitosan-coated nanoemulsion for topical therapy in wound healing. Pharmaceutics 2020 12 9 893 10.3390/pharmaceutics12090893 32962195
    [Google Scholar]
  31. Yeo E. Yew Chieng C.J. Choudhury H. Pandey M. Gorain B. Tocotrienols-rich naringenin nanoemulgel for the management of diabetic wound: Fabrication, characterization and comparative in vitro evaluations. Curr. Res. Pharmacol. Drug Disc. 2021 2 100019 10.1016/j.crphar.2021.100019 34909654
    [Google Scholar]
  32. Okur M.E. Şakul A.A. Ayla Ş. Karadağ A.E. Şenyüz C.Ş. Batur Ş. Daylan B. Özdemi̇r E.M. Yüceli̇k Ş.S. Si̇pahi̇ H. Aydin A. Wound healing effect of naringin gel in alloxan induced diabetic mice. Ankara Universitesi Eczacilik Fakultesi Dergisi 2020 44 3 397 414 10.33483/jfpau.742224
    [Google Scholar]
  33. Kandhare A.D. Alam J. Patil M.V.K. Sinha A. Bodhankar S.L. Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats. Pharm. Biol. 2016 54 3 419 432 10.3109/13880209.2015.1038755 25894211
    [Google Scholar]
  34. Sahiner M. Sahiner N. Sagbas S. Fullerton M.L. Blake D.A. Fabrication of biodegradable poly (naringin) particles with antioxidant activity and low toxicity. ACS Omega 2018 3 12 17359 17367 10.1021/acsomega.8b02292
    [Google Scholar]
  35. Miao H. Chen Z. Xu W. Wang W. Song Y. Wang Z. Preparation and characterization of naringenin microparticles via a supercritical anti-Solvent process. J. Supercrit. Fluids 2018 131 19 25 10.1016/j.supflu.2017.08.013
    [Google Scholar]
  36. Balachandran A. Choi S.B. Beata M.M. Małgorzata J. Froemming G.R.A. Lavilla C.A. Jr Billacura M.P. Siyumbwa S.N. Okechukwu P.N. Antioxidant, wound healing potential and in silico assessment of naringin, eicosane and octacosane. Molecules 2023 28 3 1043 10.3390/molecules28031043 36770709
    [Google Scholar]
  37. Ji P. Yu T. Liu Y. Jiang J. Xu J. Zhao Y. Hao Y. Qiu Y. Zhao W. Wu C. Naringenin-loaded solid lipid nanoparticles: Preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics. Drug Des. Devel. Ther. 2016 10 911 925 27041995
    [Google Scholar]
  38. Vabeiryureilai M. Lalrinzuali K. Jagetia G.C. NF-κB and COX-2 repression with topical application of hesperidin and naringin hydrogels augments repair and regeneration of deep dermal wounds. Burns 2022 48 1 132 145 10.1016/j.burns.2021.04.016 33972147
    [Google Scholar]
  39. Quintão W.S.C. Silva-Carvalho A.E. Hilgert L.A. Gratieri T. Cunha-Filho M. Saldanha-Araújo F. Gelfuso G.M. Anti-inflammatory effect evaluation of naringenin and its incorporation into a chitosan-based film for transdermal delivery. Int. J. Pharm. 2022 627 122231 10.1016/j.ijpharm.2022.122231 36167188
    [Google Scholar]
  40. Salehi M. Ehterami A. Farzamfar S. Vaez A. Ebrahimi-Barough S. Accelerating healing of excisional wound with alginate hydrogel containing naringenin in rat model. Drug Deliv. Transl. Res. 2021 11 1 142 153 10.1007/s13346‑020‑00731‑6 32086788
    [Google Scholar]
  41. Farzaei M.H. Derayat P. Pourmanouchehri Z. Kahrarian M. Samimi Z. Hajialyani M. Bahrami G. Hosseinzadeh L. Rashidi K. Tajehmiri A. Behbood L. Characterization and evaluation of antibacterial and wound healing activity of naringenin-loaded polyethylene glycol/polycaprolactone electrospun nanofibers. J. Drug Deliv. Sci. Technol. 2023 81 104182 10.1016/j.jddst.2023.104182
    [Google Scholar]
  42. Kaur Sandhu S. Raut J. Kumar S. Singh M. Ahmed B. Singh J. Rana V. Rishi P. Ganesh N. Dua K. Pal Kaur I. Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing. Int. J. Pharm. 2023 643 123187 10.1016/j.ijpharm.2023.123187 37394156
    [Google Scholar]
  43. Kant V. Gopal A. Pathak N.N. Kumar P. Tandan S.K. Kumar D. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Int. Immunopharmacol. 2014 20 2 322 330 10.1016/j.intimp.2014.03.009 24675438
    [Google Scholar]
  44. Li F. Shi Y. Liang J. Zhao L. Curcumin-loaded chitosan nanoparticles promote diabetic wound healing via attenuating inflammation in a diabetic rat model. J. Biomater. Appl. 2019 34 4 476 486 10.1177/0885328219860929 31280635
    [Google Scholar]
  45. Dehghani S. Dalirfardouei R. Jafari Najaf Abadi M.H. Ebrahimi Nik M. Jaafari M.R. Mahdipour E. Topical application of curcumin regulates the angiogenesis in diabetic ‐ impaired cutaneous wound. Cell Biochem. Funct. 2020 38 5 558 566 10.1002/cbf.3500 32030812
    [Google Scholar]
  46. Karri V.V.S.R. Kuppusamy G. Talluri S.V. Mannemala S.S. Kollipara R. Wadhwani A.D. Mulukutla S. Raju K.R.S. Malayandi R. Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing. Int. J. Biol. Macromol. 2016 93 Pt B 1519 1529 10.1016/j.ijbiomac.2016.05.038 27180291
    [Google Scholar]
  47. Mohanty C. Pradhan J. A human epidermal growth factor-curcumin bandage bioconjugate loaded with mesenchymal stem cell for in vivo diabetic wound healing. Mater. Sci. Eng. C 2020 111 110751 10.1016/j.msec.2020.110751 32279771
    [Google Scholar]
  48. Ranjbar-Mohammadi M. Rabbani S. Bahrami S.H. Joghataei M.T. Moayer F. Antibacterial performance and in vivo diabetic wound healing of curcumin loaded gum tragacanth/poly(ε-caprolactone) electrospun nanofibers. Mater. Sci. Eng. C 2016 69 1183 1191 10.1016/j.msec.2016.08.032 27612816
    [Google Scholar]
  49. Venkatasubbu G.D. Anusuya T. Investigation on Curcumin nanocomposite for wound dressing. Int. J. Biol. Macromol. 2017 98 366 378 10.1016/j.ijbiomac.2017.02.002 28167107
    [Google Scholar]
  50. Shende P. Gupta H. Formulation and comparative characterization of nanoparticles of curcumin using natural, synthetic and semi-synthetic polymers for wound healing. Life Sci. 2020 253 117588 10.1016/j.lfs.2020.117588 32220621
    [Google Scholar]
  51. Rezaei M. Oryan S. Nourani M.R. Mofid M. Mozafari M. Curcumin nanoparticle-incorporated collagen/chitosan scaffolds for enhanced wound healing. Bioinspired, Biomimetic Nanobiomater. 2018 7 3 159 166 10.1680/jbibn.17.00036
    [Google Scholar]
  52. Andrabi S.M. Majumder S. Gupta K.C. Kumar A. Dextran based amphiphilic nano-hybrid hydrogel system incorporated with curcumin and cerium oxide nanoparticles for wound healing. Colloids Surf. B Biointerfaces 2020 195 111263 10.1016/j.colsurfb.2020.111263 32717624
    [Google Scholar]
  53. Ahmad N Ahmad R Al-Qudaihi A Alaseel SE Fita IZ Khalid MS Pottoo FH Bolla SR A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation. 3 Biotech. 2019 9 10 360
    [Google Scholar]
  54. Alibolandi M. Mohammadi M. Taghdisi S.M. Abnous K. Ramezani M. Synthesis and preparation of biodegradable hybrid dextran hydrogel incorporated with biodegradable curcumin nanomicelles for full thickness wound healing. Int. J. Pharm. 2017 532 1 466 477 10.1016/j.ijpharm.2017.09.042 28927842
    [Google Scholar]
  55. Ahmad N. Ahmad R. Al-Qudaihi A. Alaseel S.E. Fita I.Z. Khalid M.S. Pottoo F.H. Preparation of a novel curcumin nanoemulsion by ultrasonication and its comparative effects in wound healing and the treatment of inflammation. RSC Advances 2019 9 35 20192 20206 10.1039/C9RA03102B 35514703
    [Google Scholar]
  56. Hussain Z. Pandey M. Choudhury H. Ying P.C. Xian T.M. Kaur T. Jia G.W. Gorain B. Hyaluronic acid functionalized nanoparticles for simultaneous delivery of curcumin and resveratrol for management of chronic diabetic wounds: Fabrication, characterization, stability and in vitro release kinetics. J. Drug Deliv. Sci. Technol. 2020 57 101747 10.1016/j.jddst.2020.101747
    [Google Scholar]
  57. Zhao C.C. Zhu L. Wu Z. Yang R. Xu N. Liang L. Resveratrol-loaded peptide-hydrogels inhibit scar formation in wound healing through suppressing inflammation. Regen. Biomater. 2020 7 1 99 107 32440361
    [Google Scholar]
  58. Singh A. Iqubal M.K. Mittal S. Qizilbash F.F. Sartaz A. Kumar S. Ali J. Baboota S. Designing and evaluation of dermal targeted combinatorial nanostructured lipid carrier gel loaded with curcumin and resveratrol for accelerating cutaneous wound healing. Particul. Sci. Technol. 2024 42 1 88 106 10.1080/02726351.2023.2205348
    [Google Scholar]
  59. Amanat S. Taymouri S. Varshosaz J. Minaiyan M. Talebi A. Carboxymethyl cellulose-based wafer enriched with resveratrol-loaded nanoparticles for enhanced wound healing. Drug Deliv. Transl. Res. 2020 10 5 1241 1254 10.1007/s13346‑020‑00711‑w 31981141
    [Google Scholar]
  60. Jee J.P. Pangeni R. Jha S.K. Byun Y. Park J.W. Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy. Int. J. Nanomedicine 2019 14 5449 5475 10.2147/IJN.S213883 31409998
    [Google Scholar]
  61. Choudhary A. Kant V. Jangir B.L. Joshi V.G. Quercetin loaded chitosan tripolyphosphate nanoparticles accelerated cutaneous wound healing in Wistar rats. Eur. J. Pharmacol. 2020 880 173172 10.1016/j.ejphar.2020.173172 32407724
    [Google Scholar]
  62. Jangde R. Srivastava S. Singh M.R. Singh D. In vitro and in vivo characterization of quercetin loaded multiphase hydrogel for wound healing application. Int. J. Biol. Macromol. 2018 115 1211 1217 10.1016/j.ijbiomac.2018.05.010 29730004
    [Google Scholar]
  63. Jangde R. Singh D. Preparation and optimization of quercetin-loaded liposomes for wound healing, using response surface methodology. Artif. Cells Nanomed. Biotechnol. 2016 44 2 635 641 10.3109/21691401.2014.975238 25375215
    [Google Scholar]
  64. Bairagi U. Mittal P. Singh J. Mishra B. Preparation, characterization, and in vivo evaluation of nano formulations of ferulic acid in diabetic wound healing. Drug Dev. Ind. Pharm. 2018 44 11 1783 1796 10.1080/03639045.2018.1496448 29973105
    [Google Scholar]
  65. Poornima B. Korrapati P.S. Fabrication of chitosan-polycaprolactone composite nanofibrous scaffold for simultaneous delivery of ferulic acid and resveratrol. Carbohydr. Polym. 2017 157 1741 1749 10.1016/j.carbpol.2016.11.056 27987890
    [Google Scholar]
  66. Anand S. Pandey P. Begum M.Y. Chidambaram K. Arya D.K. Gupta R.K. Sankhwar R. Jaiswal S. Thakur S. Rajinikanth P.S. Electrospun biomimetic multifunctional nanofibers loaded with ferulic acid for enhanced antimicrobial and wound-healing activities in STZ-Induced diabetic rats. Pharmaceuticals (Basel) 2022 15 3 302 10.3390/ph15030302 35337100
    [Google Scholar]
  67. Aggarwal BB Kumar A Bharti AC Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 2003 23 10A 363 98
    [Google Scholar]
  68. Ansari L. Mashayekhi-Sardoo H. Baradaran Rahimi V. Yahyazadeh R. Ghayour-Mobarhan M. Askari V.R. Curcumin‐based nanoformulations alleviate wounds and related disorders: A comprehensive review. Biofactors 2023 49 4 736 781 10.1002/biof.1945 36961254
    [Google Scholar]
  69. Sharma A. Dheer D. Singh I. Puri V. Kumar P. Phytoconstituent-loaded nanofibrous meshes as wound dressings: A concise review. Pharmaceutics 2023 15 4 1058 10.3390/pharmaceutics15041058 37111544
    [Google Scholar]
  70. Pignet A.L. Schellnegger M. Hecker A. Kohlhauser M. Kotzbeck P. Kamolz L.P. Resveratrol-induced signal transduction in wound healing. Int. J. Mol. Sci. 2021 22 23 12614 10.3390/ijms222312614 34884419
    [Google Scholar]
  71. D’Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia 2015 106 256 271 10.1016/j.fitote.2015.09.018 26393898
    [Google Scholar]
  72. Tomou E.M. Papakyriakopoulou P. Saitani E.M. Valsami G. Pippa N. Skaltsa H. Recent advances in nanoformulations for quercetin delivery. Pharmaceutics 2023 15 6 1656 10.3390/pharmaceutics15061656 37376104
    [Google Scholar]
  73. Wadhwa K. Kadian V. Puri V. Bhardwaj B.Y. Sharma A. Pahwa R. Rao R. Gupta M. Singh I. New insights into quercetin nanoformulations for topical delivery. Phytomedicine Plus 2022 2 2 100257 10.1016/j.phyplu.2022.100257
    [Google Scholar]
  74. Boz H. Ferulic acid in cereals - a review. Czech J. Food Sci. 2015 33 1 1 7 10.17221/401/2014‑CJFS
    [Google Scholar]
  75. Shukla D. Nandi N.K. Singh B. Singh A. Kumar B. Narang R.K. Singh C. Ferulic acid-loaded drug delivery systems for biomedical applications. J. Drug Deliv. Sci. Technol. 2022 75 103621 10.1016/j.jddst.2022.103621
    [Google Scholar]
  76. Lobiuc A. Pavăl N.E. Mangalagiu I.I. Gheorghiță R. Teliban G.C. Amăriucăi-Mantu D. Stoleru V. Future antimicrobials: Natural and functionalized phenolics. Molecules 2023 28 3 1114 10.3390/molecules28031114 36770780
    [Google Scholar]
  77. Zhang H. Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr. Opin. Food Sci. 2016 8 33 42 10.1016/j.cofs.2016.02.002
    [Google Scholar]
  78. Jin L. Zeng W. Zhang F. Zhang C. Liang W. Naringenin ameliorates acute inflammation by regulating intracellular cytokine degradation. J. Immunol. 2017 199 10 3466 3477 10.4049/jimmunol.1602016 28993518
    [Google Scholar]
  79. Basiouni S. Tellez-Isaias G. Latorre J.D. Graham B.D. Petrone-Garcia V.M. El-Seedi H.R. Yalçın S. El-Wahab A.A. Visscher C. May-Simera H.L. Huber C. Eisenreich W. Shehata A.A. Anti-Inflammatory and antioxidative phytogenic substances against secret killers in poultry: Current Status and Prospects. Vet. Sci. 2023 10 1 55 10.3390/vetsci10010055 36669057
    [Google Scholar]
  80. Yang J. Liu L. Li M. Huang X. Yang H. Li K. Naringenin inhibits pro‑inflammatory cytokine production in macrophages through inducing MT1G to suppress the activation of NF‑κB. Mol. Immunol. 2021 137 155 162 10.1016/j.molimm.2021.07.003 34252709
    [Google Scholar]
  81. Shilpa V.S. Shams R. Dash K.K. Pandey V.K. Dar A.H. Ayaz Mukarram S. Harsányi E. Kovács B. Phytochemical properties, extraction, and pharmacological benefits of naringin: A review. Molecules 2023 28 15 5623 10.3390/molecules28155623 37570594
    [Google Scholar]
  82. Xu F.W. Lv Y.L. Zhong Y.F. Xue Y.N. Wang Y. Zhang L.Y. Hu X. Tan W.Q. Beneficial effects of green tea EGCG on skin wound healing: A comprehensive review. Molecules 2021 26 20 6123 10.3390/molecules26206123 34684703
    [Google Scholar]
  83. Sun R. Liu C. Liu J. Yin S. Song R. Ma J. Cao G. Lu Y. Zhang G. Wu Z. Chen A. Wang Y. Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds. Sci. Rep. 2023 13 1 132 10.1038/s41598‑022‑26043‑y 36599852
    [Google Scholar]
  84. Zhang Y. Wang J. Zhou S. Xie Z. Wang C. Gao Y. Zhou J. Zhang X. Li Q. Flavones hydroxylated at 5, 7, 3′ and 4′ ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity. Cell Death Dis. 2019 10 2 124 10.1038/s41419‑019‑1333‑7 30741930
    [Google Scholar]
  85. Zhang M. Chen X. Zhang Y. Zhao X. Zhao J. Wang X. The potential of functionalized dressing releasing flavonoids facilitates scar-free healing. Front. Med. (Lausanne) 2022 9 978120 10.3389/fmed.2022.978120 36262272
    [Google Scholar]
  86. Emad NA Zai I Ahmad S Pandit J Khan MA Sultana Y Role of polyphenols, their nano-formulations, and biomaterials in diabetic wound healing. Endocr Metab Immune Disord Drug Targets 2024 24 6 626 641 10.2174/0118715303242310230927104709
    [Google Scholar]
  87. Mehta P. Sharma M. Devi M. Hydrogels: An overview of its classifications, properties, and applications. J. Mech. Behav. Biomed. Mater. 2023 147 106145 10.1016/j.jmbbm.2023.106145 37797557
    [Google Scholar]
  88. Ali A Ahmed S An introduction to hydrogels. Polysaccharides-Based Hydrogels: Synthesis Characterization and Applications Amsterdam Elsevier 2024 10.1016/B978‑0‑323‑99341‑8.00001‑6
    [Google Scholar]
  89. Zamani A. Taherzadeh M.J. Effects of partial dehydration and freezing temperature on the morphology and water binding capacity of carboxymethyl chitosan-based superabsorbents. Ind. Eng. Chem. Res. 2010 49 17 8094 8099 10.1021/ie100257s
    [Google Scholar]
  90. Adair A. Kaesaman A. Klinpituksa P. Superabsorbent materials derived from hydroxyethyl cellulose and bentonite: Preparation, characterization and swelling capacities. Polym. Test. 2017 64 321 329 10.1016/j.polymertesting.2017.10.018
    [Google Scholar]
  91. Varghese SA Rangappa SM Siengchin S Parameswaranpillai J Natural polymers and the hydrogels prepared from them. Hydrogels Based on Natural Polymers Amsterdam Elsevier 2020 10.1016/B978‑0‑12‑816421‑1.00002‑1
    [Google Scholar]
  92. Ullah F. Othman M.B.H. Javed F. Ahmad Z. Akil H.M. Classification, processing and application of hydrogels: A review. Mater. Sci. Eng. C 2015 57 414 433 10.1016/j.msec.2015.07.053 26354282
    [Google Scholar]
  93. Koetting M.C. Peters J.T. Steichen S.D. Peppas N.A. Stimulus-responsive hydrogels: Theory, modern advances, and applications. Mater. Sci. Eng. Rep. 2015 93 1 49 10.1016/j.mser.2015.04.001 27134415
    [Google Scholar]
  94. Zhang S. Ge G. Qin Y. Li W. Dong J. Mei J. Ma R. Zhang X. Bai J. Zhu C. Zhang W. Geng D. Recent advances in responsive hydrogels for diabetic wound healing. Mater. Today Bio 2023 18 100508 10.1016/j.mtbio.2022.100508 36504542
    [Google Scholar]
  95. Kesharwani P. Bisht A. Alexander A. Dave V. Sharma S. Biomedical applications of hydrogels in drug delivery system: An update. J. Drug Deliv. Sci. Technol. 2021 66 102914 10.1016/j.jddst.2021.102914
    [Google Scholar]
  96. Tavakoli S. Klar A.S. Advanced hydrogels as wound dressings. Biomolecules 2020 10 8 1169 10.3390/biom10081169 32796593
    [Google Scholar]
  97. Kaur M. Sharma A. Puri V. Aggarwal G. Maman P. Huanbutta K. Nagpal M. Sangnim T. Chitosan-based polymer blends for drug delivery systems. Polymers (Basel) 2023 15 9 2028 10.3390/polym15092028 37177176
    [Google Scholar]
  98. Pandey S. Shamim A. Shaif M. Kushwaha P. Development and evaluation of Resveratrol-loaded liposomes in hydrogel-based wound dressing for diabetic foot ulcer. Naunyn Schmiedebergs Arch. Pharmacol. 2023 396 8 1811 1825 10.1007/s00210‑023‑02441‑5 36862150
    [Google Scholar]
  99. Rezvanian M. Ng S.F. Alavi T. Ahmad W. In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic wound healing in Streptozotocin-induced diabetic rats. Int. J. Biol. Macromol. 2021 171 308 319 10.1016/j.ijbiomac.2020.12.221 33421467
    [Google Scholar]
  100. Zhao L. Niu L. Liang H. Tan H. Liu C. Zhu F. pH and glucose dual-responsive injectable hydrogels with insulin and fibroblasts as bioactive dressings for diabetic wound healing. ACS Appl. Mater. Interfaces 2017 9 43 37563 37574 10.1021/acsami.7b09395 28994281
    [Google Scholar]
  101. Lee Y.H. Lin S.J. Chitosan/PVA hetero-composite hydrogel containing antimicrobials, perfluorocarbon nanoemulsions, and growth factor-loaded nanoparticles as a multifunctional dressing for diabetic wound healing: Synthesis, characterization, and in vitro/in vivo evaluation. Pharmaceutics 2022 14 3 537 10.3390/pharmaceutics14030537 35335913
    [Google Scholar]
  102. El-Salamouni N.S. Gowayed M.A. Seiffein N.L. Abdel- Moneim R.A. Kamel M.A. Labib G.S. Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study. Int. J. Pharm. 2021 592 120091 10.1016/j.ijpharm.2020.120091 33197564
    [Google Scholar]
  103. Li Z. Zhao Y. Liu H. Ren M. Wang Z. Wang X. Liu H. Feng Y. Lin Q. Wang C. Wang J. pH-responsive hydrogel loaded with insulin as a bioactive dressing for enhancing diabetic wound healing. Mater. Des. 2021 210 110104 10.1016/j.matdes.2021.110104
    [Google Scholar]
  104. Lee Y.H. Hong Y.L. Wu T.L. Novel silver and nanoparticle-encapsulated growth factor co-loaded chitosan composite hydrogel with sustained antimicrobility and promoted biological properties for diabetic wound healing. Mater. Sci. Eng. C 2021 118 111385 10.1016/j.msec.2020.111385 33254992
    [Google Scholar]
  105. Badhwar R. Mangla B. Neupane Y.R. Khanna K. Popli H. Quercetin loaded silver nanoparticles in hydrogel matrices for diabetic wound healing. Nanotechnology 2021 32 50 505102 10.1088/1361‑6528/ac2536 34500444
    [Google Scholar]
  106. Chen G. He L. Zhang P. Zhang J. Mei X. Wang D. Zhang Y. Ren X. Chen Z. Encapsulation of green tea polyphenol nanospheres in PVA/alginate hydrogel for promoting wound healing of diabetic rats by regulating PI3K/AKT pathway. Mater. Sci. Eng. C 2020 110 110686 10.1016/j.msec.2020.110686 32204114
    [Google Scholar]
  107. Masood N. Ahmed R. Tariq M. Ahmed Z. Masoud M.S. Ali I. Asghar R. Andleeb A. Hasan A. Silver nanoparticle impregnated chitosan-PEG hydrogel enhances wound healing in diabetes induced rabbits. Int. J. Pharm. 2019 559 23 36 10.1016/j.ijpharm.2019.01.019 30668991
    [Google Scholar]
  108. Kamar S.S. Abdel-Kader D.H. Rashed L.A. Beneficial effect of Curcumin Nanoparticles-Hydrogel on excisional skin wound healing in type-I diabetic rat: Histological and immunohistochemical studies. Ann. Anat. 2019 222 94 102 10.1016/j.aanat.2018.11.005 30521949
    [Google Scholar]
  109. Ding Z. Zhang Y. Guo P. Duan T. Cheng W. Guo Y. Zheng X. Lu G. Lu Q. Kaplan D.L. Injectable desferrioxamine-laden silk nanofiber hydrogels for accelerating diabetic wound healing. ACS Biomater. Sci. Eng. 2021 7 3 1147 1158 10.1021/acsbiomaterials.0c01502 33522800
    [Google Scholar]
  110. Fan Y. Wu W. Lei Y. Gaucher C. Pei S. Zhang J. Xia X. Edaravone-loaded alginate-based nanocomposite hydrogel accelerated chronic wound healing in diabetic mice. Mar. Drugs 2019 17 5 285 10.3390/md17050285 31083588
    [Google Scholar]
  111. Park Y.G. Lee I.H. Park E.S. Kim J.Y. Hydrogel and platelet-rich plasma combined treatment to accelerate wound healing in a nude mouse model. Arch. Plast. Surg. 2017 44 3 194 201 10.5999/aps.2017.44.3.194 28573093
    [Google Scholar]
  112. Badhwar R. Singh R. Popli H. Implementation of quality by design (qbd) approach in development of qct-smedds with combination of agnps for diabetic foot ulcer management. Indian J. Pharm. Educ. Res. 2021 55 1207 1223
    [Google Scholar]
  113. Liu M. Liu T. Chen X. Yang J. Deng J. He W. Zhang X. Lei Q. Hu X. Luo G. Wu J. Nano-silver-incorporated biomimetic polydopamine coating on a thermoplastic polyurethane porous nanocomposite as an efficient antibacterial wound dressing. J. Nanobiotechnol. 2018 16 1 89 10.1186/s12951‑018‑0416‑4 30419925
    [Google Scholar]
  114. Renuka R.R. Julius A. Yoganandham S.T. Umapathy D. Ramadoss R. Samrot A.V. Vijay D.D. Diverse nanocomposites as a potential dressing for diabetic wound healing. Front. Endocrinol. (Lausanne) 2023 13 1074568 10.3389/fendo.2022.1074568 36714604
    [Google Scholar]
  115. Nagarjuna Reddy V. Nyamathulla S. Abdul Kadir Pahirulzaman K. Mokhtar S.I. Giribabu N. Pasupuleti V.R. Gallocatechin-silver nanoparticles embedded in cotton gauze patches accelerated wound healing in diabetic rats by promoting proliferation and inhibiting apoptosis through the Wnt/β-catenin signaling pathway. PLoS One 2022 17 6 e0268505 10.1371/journal.pone.0268505 35737691
    [Google Scholar]
  116. Gupta A. Briffa S.M. Swingler S. Gibson H. Kannappan V. Adamus G. Kowalczuk M. Martin C. Radecka I. Synthesis of silver nanoparticles using curcumin-cyclodextrins loaded into bacterial cellulose-based hydrogels for wound dressing applications. Biomacromolecules 2020 21 5 1802 1811 10.1021/acs.biomac.9b01724 31967794
    [Google Scholar]
  117. Kaur P. Sharma A.K. Nag D. Das A. Datta S. Ganguli A. Goel V. Rajput S. Chakrabarti G. Basu B. Choudhury D. Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing. Nanomedicine 2019 15 1 47 57 10.1016/j.nano.2018.08.013 30213518
    [Google Scholar]
  118. Anisha B.S. Biswas R. Chennazhi K.P. Jayakumar R. Chitosan–hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds. Int. J. Biol. Macromol. 2013 62 310 320 10.1016/j.ijbiomac.2013.09.011 24060281
    [Google Scholar]
  119. Gainza G. Aguirre J.J. Pedraz J.L. Hernández R.M. Igartua M. rhEGF-loaded PLGA-Alginate microspheres enhance the healing of full-thickness excisional wounds in diabetised Wistar rats. Eur. J. Pharm. Sci. 2013 50 3-4 243 252 10.1016/j.ejps.2013.07.003 23872142
    [Google Scholar]
  120. Gainza G. Pastor M. Aguirre J.J. Villullas S. Pedraz J.L. Hernandez R.M. Igartua M. A novel strategy for the treatment of chronic wounds based on the topical administration of rhEGF-loaded lipid nanoparticles: In vitro bioactivity and in vivo effectiveness in healing-impaired db/db mice. J. Control. Release 2014 185 51 61 10.1016/j.jconrel.2014.04.032 24794895
    [Google Scholar]
  121. Salem H.F. Nafady M.M. Ewees M.G.E.L.D. Hassan H. Khallaf R.A. Rosuvastatin calcium-based novel nanocubic vesicles capped with silver nanoparticles-loaded hydrogel for wound healing management: Optimization employing Box–Behnken design: In vitro and in vivo assessment. J. Liposome Res. 2022 32 1 45 61 10.1080/08982104.2020.1867166 33353435
    [Google Scholar]
  122. Liu Q. Zhang Y. Huang J. Xu Z. Li X. Yang J. Huang H. Tang S. Chai Y. Lin J. Yang C. Liu J. Lin S. Mesoporous silica-coated silver nanoparticles as ciprofloxacin/siRNA carriers for accelerated infected wound healing. J. Nanobiotechnol. 2022 20 1 386 10.1186/s12951‑022‑01600‑9 35999547
    [Google Scholar]
  123. Choudhury H. Pandey M. Lim Y.Q. Low C.Y. Lee C.T. Marilyn T.C.L. Loh H.S. Lim Y.P. Lee C.F. Bhattamishra S.K. Kesharwani P. Gorain B. Silver nanoparticles: Advanced and promising technology in diabetic wound therapy. Mater. Sci. Eng. C 2020 112 110925 10.1016/j.msec.2020.110925 32409075
    [Google Scholar]
  124. Salunkhe J.D. Mohite B.V. Patil S.V. Naringenin biosynthesis and fabrication of naringenin mediated nano silver conjugate for antimicrobial potential. Nat. Prod. Res. 2023 37 18 3184 3190 10.1080/14786419.2022.2147931 36412534
    [Google Scholar]
  125. University of Guadalajara Efficacy of the combination of isosorbide dinitrate spray and chitosan in diabetic foot ulcers. 2021 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02789033
  126. Xequel Bio, Inc. Safety study to examine the Systemic Exposure of Granexin® Gel after topical application to diabetic foot ulcers. 2018 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02652754
  127. Biotec Pharmacon ASA Evaluation of Woulgan in Diabetic Foot Ulcer. 2019 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02631512
  128. Xequel Bio, Inc. A study of granexin gel in the treatment of diabetic foot ulcer. 2020 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02667327
  129. Smith & Nephew, Inc. Use of Santyl in Diabetic Foot Ulcers. 2018 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02581488
  130. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. Effect of Topic Pirfenidone in Diabetic Ulcers (PirDFI). 2016 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02222376
  131. Karyopharm Therapeutics Inc. Study of Safety, Tolerability, and Pharmacokinetics of Topical Selinexor (KPT-330) Diabetic Foot Ulcer (DFU) Patients. 2023 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02367690
  132. Royer Biomedical, Inc. Safety and Efficacy of Gentamicin Topical Gel (AppliGel-G) for Treatment of Mild to Moderately Infected Diabetic Foot Ulcers. 2015 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02036528
  133. Integra LifeSciences Corporation. Phase III Study to Evaluate Efficacy and Safety of DSC127 in Diabetic Foot Ulcers (STRIDE 1). 2017 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01830348
  134. OcuNexus Therapeutics, Inc. A study to investigate the safety and clinical effect of Nexagon® as a topical treatment for subjects with a Diabetic Foot Ulcer (DUNE) (DUNE). 2014 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01490879
  135. Oneness Biotech Co., Ltd. A Randomized,Double-blind,Placebo-controlled Clinical Study to Explore the Mechanism of Action of ON101 Cream in Patients With DFUs. 2023 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT04945161
  136. Integra LifeSciences Corporation Phase 3 Study Evaluating Efficacy and Safety of DSC127 Compared With Vehicle and With Standard-of-care in Diabetic Foot Ulcers (STRIDE 2). 2017 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01849965
  137. CoMentis Safety and preliminary efficacy study of nicotine gel to treat diabetic foot ulcers. 2007 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT00316537
  138. Abeona Therapeutics, Inc. MSI-78 Topical Cream vs. Oral Ofloxacin in the Treatment of Infected Diabetic Ulcers. 2020 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT00563433
  139. Bridge BioResearch Ltd. Oral BBR-012 in the Treatment of Diabetic Foot Ulcers, Proof of Concept Study (BBR-012). 2011 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01342497
  140. Mashhad University of Medical Sciences The effect of combination therapy of oral MB and PRP-FG in patients with non-healing diabetic foot ulcer. 2023 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT05850611
  141. Edixomed Ltd. Nitric Oxide Generating Gel Dressing in Patients With Diabetic Foot Ulcers (ProNOx1). 2016 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01982565
  142. European Egyptian Pharmaceutical Industries. Study of the Efficacy of PedyPhar® Ointment on the Diabetic Foot Ulcers (PED111). 2015 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01531517
  143. Karolinska University Hospital. Effect of Deferoxamine on Wound Healing Rate in Patients With Diabetes Foot Ulcers (DEFEHU). 2022 Available From: https://clinicaltrials.gov/study/NCT03137966
  144. Novalead Pharma Private Limited Phase 3 study to evaluate the safety and efficacy of Galnobax® in treating diabetic foot ulcers. 2023 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT03998436
  145. Hamed S. Ullmann Y. Belokopytov M. Shoufani A. Kabha H. Masri S. Feldbrin Z. Kogan L. Kruchevsky D. Najjar R. Liu P.Y. Kerihuel J.C. Akita S. Teot L. Topical erythropoietin accelerates wound closure in patients with diabetic foot ulcers: A prospective, multicenter, single-blind, randomized, controlled trial. Rejuvenation Res. 2021 24 4 251 261 10.1089/rej.2020.2397 33504262
    [Google Scholar]
  146. Remedor Biomed Ltd. Topical erythropoietin hydrogel formulation for diabetic foot ulcers (Remede d'Or). 2019 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02361931
  147. European Egyptian Pharmaceutical Industries Efficacy & Safety of pedyphar ointment in diabetic foot ulcer treatment (PEDFUT). 2015 Available From: https://classic.clinicaltrials.gov/ct2/show/NCT02379468
/content/journals/cdd/10.2174/0115672018322140241023054041
Loading
/content/journals/cdd/10.2174/0115672018322140241023054041
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test