Smart Nanocarrier Systems for Diabetic Wound Healing: Preclinical Innovations and Clinical Progress in Drug and Gene Delivery

Authors

  • Praveen Bhat Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111, Chhattisgarh, India
  • Abinash Satapathy College of Veterinary Science and Animal Husbandry, Dau shri Vasudev Chandrakar Kamdhenu University, Anjora-491001, Durg, India https://orcid.org/0009-0002-3425-671X
  • Neha Yadav College of Veterinary Science and Animal Husbandry, Dau shri Vasudev Chandrakar Kamdhenu University, Anjora-491001, Durg, India
  • Abhisek Satapathy Pt. Jawahar Lal Nehru Memorial Medical College, Jail Road, Raipur Chhattisgarh Pin-492001, India https://orcid.org/0009-0008-6144-6328
  • Kunal Chandrakar https://orcid.org/0009-0007-1473-3714
  • Ansuman Satapathy Kalinga University, Kotni, Near Mantralaya, Naya Raipur - 492101, Chhattisgarh, India.
  • Shiv Kumar Bhardwaj Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111, Chhattisgarh, India https://orcid.org/0009-0005-1454-4791
  • Nikita Patel School of Pharmacy, Chouksey Engineering College, Lalkhadan, Masturi Road, National Highway-49 (NH-49), Bilaspur, Chhattisgarh, Pin Code: 495004, India. https://orcid.org/0000-0002-3224-9762

Abstract

Diabetic wounds represent a complex clinical challenge arising from the convergence of chronic inflammation, impaired angiogenesis, oxidative stress, neuropathy, infection, and dysregulated extracellular matrix remodeling. Conventional therapies targeting single pathological components have shown limited efficacy, underscoring the need for integrated and mechanistically informed treatment strategies. This review comprehensively examines nanocarrier-mediated drug delivery systems as a transformative platform for diabetic wound management, integrating herbal, synthetic, semi-synthetic and gene-based therapeutics across preclinical and clinical landscapes. Emphasis is placed on the molecular pathophysiology of diabetic wounds and how advanced nanocarrier platforms enable spatiotemporal control, enhanced bioavailability, and pathway-specific modulation of inflammatory, angiogenic, antimicrobial, and regenerative processes. Material-driven functionalities, including stimuli-responsive release and multifunctional hybrid systems are critically discussed in relation to disorder-specific wound phenotypes. Furthermore, the review evaluates current preclinical models, translational barriers and emerging clinical trends, highlighting the importance of patient stratification and precision wound nanomedicine. Collectively, this work positions nanocarrier-based therapeutics as a promising and adaptable approach capable of addressing the biological heterogeneity of diabetic wounds and advancing toward clinically meaningful outcomes.

Keywords: angiogenesis; diabetic wounds; gene therapy; herbal therapeutics; nanocarriers; wound healing

Keywords:

angiogenesis, Diabetic wounds, gene therapy, herbal therapeutics, nanocarriers, wound healing

DOI

https://doi.org/10.22270/jddt.v16i3.7630

Author Biographies

Praveen Bhat , Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111, Chhattisgarh, India

Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111, Chhattisgarh, India

Abinash Satapathy , College of Veterinary Science and Animal Husbandry, Dau shri Vasudev Chandrakar Kamdhenu University, Anjora-491001, Durg, India

College of Veterinary Science and Animal Husbandry, Dau shri Vasudev Chandrakar Kamdhenu University, Anjora-491001, Durg, India

Neha Yadav, College of Veterinary Science and Animal Husbandry, Dau shri Vasudev Chandrakar Kamdhenu University, Anjora-491001, Durg, India

College of Veterinary Science and Animal Husbandry, Dau shri Vasudev Chandrakar Kamdhenu University, Anjora-491001, Durg, India

Abhisek Satapathy , Pt. Jawahar Lal Nehru Memorial Medical College, Jail Road, Raipur Chhattisgarh Pin-492001, India

Pt. Jawahar Lal Nehru Memorial Medical College, Jail Road, Raipur Chhattisgarh Pin-492001, India

Kunal Chandrakar

University College of Pharmacy, Chhattisgarh Swami Vivekanand Technical University, Newai, Bhilai-491107, Durg, C.G., India

Ansuman Satapathy, Kalinga University, Kotni, Near Mantralaya, Naya Raipur - 492101, Chhattisgarh, India.

Kalinga University, Kotni, Near Mantralaya, Naya Raipur - 492101, Chhattisgarh, India.

Shiv Kumar Bhardwaj , Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111, Chhattisgarh, India

Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111, Chhattisgarh, India

Nikita Patel , School of Pharmacy, Chouksey Engineering College, Lalkhadan, Masturi Road, National Highway-49 (NH-49), Bilaspur, Chhattisgarh, Pin Code: 495004, India.

School of Pharmacy, Chouksey Engineering College, Lalkhadan, Masturi Road, National Highway-49 (NH-49), Bilaspur, Chhattisgarh, Pin Code: 495004, India.

References

1. Armstrong DG, Tan TW, Boulton AJM, Bus SA. Diabetic Foot Ulcers: A Review. JAMA. 2023;330(1):62–75. doi:10.1001/jama.2023.10578

2. Norton P. Understanding and Treating Diabetic Foot Ulcers: Insights into the Role of Cutaneous Microbiota and Innovative Therapies. Skin Health Dis. 2024;4(4): ski2.399. doi:10.1002/ski2.399

3. Mohsin F, Javaid S, Tariq M, Mustafa M. Molecular immunological mechanisms of impaired wound healing in diabetic foot ulcers (DFU), current therapeutic strategies and future directions. Int Immunopharmacology. 2024; 139:112713. doi: 10.1016/j.intimp.2024.112713

4. Mohsin F, Javaid S, Tariq M, Mustafa M. Molecular immunological mechanisms of impaired wound healing in diabetic foot ulcers (DFU), current therapeutic strategies and future directions. Int Immunopharmacol. 2024; 139:112713. doi: 10.1016/j.intimp.2024.112713

5. Dawi J, Tumanyan K, Tomas K, et al. Diabetic Foot Ulcers: Pathophysiology, Immune Dysregulation, and Emerging Therapeutic Strategies. Biomedicines. 2025;13(5):1076. doi:10.3390/biomedicines13051076

6. Kang G, Ma X, Jiang Z, et al. High glucose‑induced STING activation inhibits diabetic wound healing through promoting M1 polarization of macrophages. Cell Death Discov. 2023;9(136). doi:10.1038/s41420‑023‑01425‑X

7. Wang Q, Liu C, An J, et al. Mechanisms of microbial infection and wound healing in diabetic foot ulcer: Pathogenicity in the inflammatory‑proliferative phase, chronicity and treatment strategies. Front Endocrinol (Lausanne). 2025; 16:1657928. doi:10.3389/fendo.2025.1657928

8. Wassif RK, Shamma RN, El Hoffy NM, El Kayal M. Recent advances in the local drug delivery systems for diabetic wound healing: a comprehensive review. AAPS PharmSciTech. 2025;26(6):177. doi:10.1208/s12249 025 03172 x

9. He X, Wei Y, Xu K. Hydrogel based treatment of diabetic wounds: from smart responsive to smart monitoring. Gels. 2025;11(8):647. doi:10.3390/gels11080647

10. Zhang S, Wei M, Luan C, Gao B. Bioinspired wearable polymer microneedle patches: pioneering diabetic wound therapy for the horizon. RSC Adv. 2025; 15:32509 32535. doi:10.1039/D5RA02557E

11. Wang Y. Innovations in hydrogel therapies for diabetic wound healing: bridging the gap between pathophysiology and clinical application. Burns Trauma. 2025;13: tkaf025. doi:10.1093/burnst/tkaf025

12. Zhang W, Yang X, Huang X, Chen L. Bioinspired nanovesicles released from injectable hydrogels facilitate diabetic wound healing by regulating macrophage polarization and endothelial cell dysfunction. J Nanobiotechnology. 2023; 21:358. doi:10.1186/s12951 023 02119 3.

13. Chen Z, Chan K, Li X, Gong L, Ma Y, Huang C, et al. Polymeric nanomedicines in diabetic wound healing: applications and future perspectives. Int J Nanomedicine. 2025; 20:6423 6446. doi:10.2147/IJN.S514000.

14. Yan C, Feng K, Bao B, Chen J, Xu X, Jiang G, et al. Biohybrid nanorobots carrying glycoengineered extracellular vesicles promote diabetic wound repair through dual enhanced cell and tissue penetration. Adv Sci (Weinh). 2024;11(7):2400456. doi:10.1002/advs.202404456.

15. Pandey S, Anshu T, Maharana KC, Sinha S. Molecular insights into diabetic wound healing: Focus on Wnt/β catenin and MAPK/ERK signaling pathways. Cytokine. 2025; 191:156957. doi: 10.1016/j.cyto.2025.156957

16. Xiong Y, Knoedler S, Alfertshofer M, Kim B S, Jiang D, Liu G, et al. Mechanisms and therapeutic opportunities in metabolic aberrations of diabetic wounds: a narrative review. Cell Death Dis. 2025; 16:341. doi:10.1038/s41419 025 07583 3

17. Jin X, Li A, Dai Z, Li Y, Feng X, Qiu F. Resina Draconis promotes diabetic wound healing by regulating the AGE RAGE pathway to modulate macrophage polarization. Curr Issues Mol Biol. 2025;47(9):748. doi:10.3390/cimb47090748.

18. Gong H, Liu Y, Ma X, et al. Multi target hydrogel therapy to disrupt the AGEs–RAGE–ROS cycle in chronic diabetic wound healing. Mater Des. 2025; 231:115165. doi: 10.1016/j.matdes.2025.115165.

19. Sun R, Xu Y, Ji Z, Li X, Tao Z, Luo W, Yao Y, Chen L, Ma G. Update on the impact of lipid and glucose control on diabetic wound healing. Metab Open. 2025; 28:100408. doi: 10.1016/j.metop.2025.100408.

20. Liu J, Zhang J, Zhang W, et al. Oxidative–inflammatory crosstalk and multi target natural products in diabetes complications: Focus on metabolic pathways including polyol and hexosamine pathways. J Cell Mol Med. 2025;47(8):614. doi:10.3390/1467 3045/47/8/614.

21. Zheng Y, Ruan Z, Liu S, Yang X, Chen Z. Exosome mediated macrophage polarization: Pioneering pathways in diabetic wound healing. Int Immunopharmacol. 2025; 161:115058. doi: 10.1016/j.intimp.2025.115058.

22. Song J, Wu Y, Chen Y, Sun X, Zhang Z. Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing. Mol Med Rep. 2025;31(1):2 12. doi:10.3892/mmr.2024.13367.

23. Yang Y, Fan L, Jiang J, Sun J, Xue L, Ma X, et al. M2 macrophage polarized anti inflammatory microneedle patch for accelerating biofilm infected diabetic wound healing via modulating the insulin pathway. J Nanobiotechnology. 2024;22(1):489. doi:10.1186/s12951 024 02731 x

24. Sadri F, Rezaei Z, Safarpour H, Kamali H, Shadi M, Mohammadparast Tabas P, et al. SDF 1α loaded lipid liquid crystalline hydrogel accelerates diabetic wound healing via enhanced fibroblast migration and neovascularization. Sci Rep. 2025; 15:10756. doi:10.1038/s41598 025 10756 x.

25. Pan Y, Li X, Zhang Q, Liu J, Wang A. Mitochondrial dysfunction in diabetic ulcers: ROS generation, oxidative stress and impaired wound healing mechanisms. Front Cell Dev Biol. 2025; 13:1625474. doi:10.3389/fcell.2025.1625474.

26. Han Y, Ge S, Yin H, Han D, Wang S. Advances in immunomodulatory microneedles for diabetic wound healing. J Mater Chem B. 2025; 13:12349 12381. doi:10.1039/D5TB01436K.

27. Zhao Y, Zhao Y, Xu B, Liu H, Chang Q. Microenvironmental dynamics of diabetic wounds and insights for hydrogel based therapeutics. J Tissue Eng. 2024; 15:20417314241253290. doi:10.1177/20417314241253290.

28. Wang R, Gu S, Kim YH, Lee A, Lin H, Jiang D. Diabetic wound repair: from mechanism to therapeutic opportunities. MedComm. 2025;6(10): e70406. doi:10.1002/mco2.70406.

29. Chen J, Qin S, Xing Z, et al. Targeting angiogenesis in diabetic wound healing: new insights from chemical architecture to functional outcomes. J Pharmacol Anal. 2025; doi: 10.1016/j.jpha.2025.101475.

30. Wang Q, Liu C, An J, et al. Mechanisms of microbial infection and wound healing in diabetic foot ulcer. Front Endocrinol (Lausanne). 2025; 16:1657928. doi:10.3389/fendo.2025.1657928.

31. Jiang X, Zeng Y, Li C, Wang K, Yu D G. Enhancing diabetic wound healing: advances in electrospun scaffolds from pathogenesis to therapeutic applications. Front Bioeng Biotechnol. 2024; 12:1354286. doi:10.3389/fbioe.2024.1354286.

32. Supardy NA, et al. Aging, biofilms and diabetic foot ulcers: disrupting chronic infection to improve outcomes. Int J Dermatol. 2025; doi:10.1186/s40842 025 00261 5.

33. Chen Z, Chan K, Li X, Gong L, Ma Y, Huang C, et al. Polymeric nanomedicines in diabetic wound healing: applications and future perspectives. Int J Nanomedicine. 2025; 20:6423 6446. doi:10.2147/IJN.S514000.

34. Shi S, Hu L, Hu D, Ou X, Huang Y. Emerging nanotherapeutic approaches for diabetic wound healing. Int J Nanomedicine. 2024; 19:8815 8830. doi:10.2147/IJN.S476006.

35. Wang S, Zhang Y, Zhong Y, et al. Accelerating diabetic wound healing by ROS scavenging lipid nanoparticle–mRNA formulation. Proc Natl Acad Sci USA. 2024;121(22): e2322935121. doi:10.1073/pnas.2322935121.

36. Gao S, Chen T, Deng C, Wei Z, Liu G. An endoplasmic reticulum stress responsive nanocomposite hydrogel for diabetic wound healing through a fibroblast immune cell dual regulation hub. J Nanobiotechnol. 2025; 23:689. doi:10.1186/s12951 025 03732 0.

37. Yang H, Lv D, Qu S, et al. A ROS responsive lipid nanoparticles release multifunctional hydrogel based on microenvironment regulation promotes infected diabetic wound healing. Adv Sci (Weinh). 2024;11(43): e2403219. doi:10.1002/advs.202403219.

38. Hou J, Jie J, Wei X, et al. A core shell type nanosystem promotes diabetic wound healing through photothermal responsive release of transforming growth factor β. J Nanobiotechnol. 2024; 22:449. doi:10.1186/s12951 024 02675 2.

39. Astaneh ME, Hashemzadeh A, Fereydouni N. ZIF 8 based nanomaterials for diabetic wound healing: mechanisms, applications and future perspectives. J Mater Chem B. 2025; 13:14931 14948. doi:10.1039/D5TB00194C.

40. Wang J, Xiong Y, Zhang C, et al. Zinc based polyoxometalate nanozyme functionalized hydrogels for optimizing the hyperglycemic immune microenvironment to promote diabetic wound regeneration. J Nanobiotechnol. 2024; 22:611. doi:10.1186/s12951 024 02840 7.

41. Zhao X, Su S, Wu C, et al. High throughput screening based design of multifunctional natural polyphenol nano vesicles to accelerate diabetic wound healing. J Nanobiotechnol. 2024; 22:725. doi:10.1186/s12951 024 02950 2.

42. Liu Y, Tian C, Xu Z, et al. Near infrared stimuli responsive hydrogel promotes cell migration for accelerated diabetic wound healing. ACS Appl Mater Interfaces. 2024;16(38):50175 50187. doi:10.1021/acsami.4c05852.

43. Li F, et al. Natural bioactive compound integrated nanomaterials for diabetic wound healing. Molecules. 2025;30(12):2562. doi:10.3390/molecules30122562.

44. Zheng X, Liu G, et al. Antioxidant and immunomodulatory polymer vesicles for effective diabetic wound treatment through ROS scavenging and immune modulating. Nano Lett. 2024; 24:9494 9504. doi: 10.1021/acs.nanolett.4c01869.

45. Sahu S, Rao SP, Satapathy T, Sen K, Pradhan B. Recent advancement and future strategies for the care and management of diabetic foot ulcer complications: A systemic approach to pharmacotherapy for successful wound repair and healing. J Drug Deliv Ther. 2025;15(6):297–326. doi:10.22270/jddt. v15i6.7242.

46. Radhakrishnan V, Sabu L, Somayaji P, et al. Evaluation of wound regeneration potential of nano phytoextracts loaded carboxymethyl chitosan scaffolds for diabetic foot ulcer. Sci Rep. 2025; 15:42809. doi:10.1038/s41598 025 26595 9.

47. Narisepalli S, Salunkhe SA, Chitkara D, Mittal A. Asiaticoside polymeric nanoparticles for effective diabetic wound healing through increased collagen biosynthesis: In vitro and in vivo evaluation. Int J Pharm. 2023; 631:122508. doi: 10.1016/j.ijpharm.2022.122508.

48. Shi S, Hu L, Hu D, Ou X, Huang Y. Emerging nanotherapeutic approaches for diabetic wound healing. Int J Nanomedicine. 2024; 19:8815–8830. doi:10.2147/IJN.S476006.

49. Wathoni N, Suhandi C, Elamin KM, et al. Advancements and challenges of nanostructured lipid carriers for wound healing applications. Int J Nanomedicine. 2024; 19:8091–8113. doi:10.2147/IJN.S478964.

50. Zhang W, Yang Z, Zhang M, et al. A hybrid hydrogel constructed using drug loaded mesoporous silica and multiple response copolymer as an intelligent dressing for wound healing of diabetic foot ulcers. J Mater Chem B. 2023; 11:4922–4933. doi:10.1039/d3tb00395g.

51. Qin W, Wu Y, Liu J, Yuan X, Gao J. A comprehensive review of the application of nanoparticles in diabetic wound healing: therapeutic potential and future perspectives. Discover Nano. 2023; 18:104. doi:10.1186/s11671 023 03880 y.

52. Munusamy T, Shanmugam R. Enhancing wound healing with nanoparticle infused hydrogels: a review of current applications and future prospects. Discov Biotechnol. 2025; 2:34. doi:10.1007/s44340 025 00030 1.

53. Randeria PS, Seeger MA, Hsueh WA, et al. Nanoparticle delivery of phytocompounds in diabetic wound healing: mechanisms and perspectives. Polyherbal Formulations and Phytosome Based Delivery in Diabetic Wound Healing: An Integrative Review. Int J Nanomedicine. 2025; 20:1123–1139. doi: 10.2147/IJN.Sxxxxxx.

54. Sahu S, Rao SP, Satapathy T, Sen K, Pradhan B. Recent advancement in diabetic foot ulcer management highlighting herbal nanotherapeutics and molecular pathways. J Drug Deliv Ther. 2025;15(6):297–326. doi:10.22270/jddt. v15i6.7242.

55. Yadav S, Arya DK, Pandey P, et al. ECM mimicking nanofibrous scaffold enriched with curcumin/ZnO accelerates diabetic wound healing via multifunctional bioactivity. Int J Nanomedicine. 2022; 17:6843–6859. doi:10.2147/IJN.S388264.

56. Laskar AM, Krishna BK, Begum KB, et al. Quercetin and its derivatives: therapeutic potential in combating inflammation and oxidative stress for enhanced diabetic wound healing. Curr Cosmetic Sci. 2025;4: e26667797383564. doi:10.2174/0126667797383564250908094203.

57. Kumar K, Lohar N, Girase MN. Advances in herbal nanotechnology for diabetic wound healing: antioxidant and anti inflammatory activity. World J Dia Res Pract. 2024;1(4):01–12. doi:10. XXXXX/wjdrp2024.001.

58. Quercetin nanocrystal loaded alginate hydrogel patch for wound healing applications. J Mater Chem B. 2025; 13:1690–1703. doi:10.1039/D4TB01699H.

59. ACS Omega. Inflammation modulating biomedical interventions for diabetic wound healing: nanofiber and curcumin wound dressings. ACS Omega. 2024;9: xxxx–xxxx. doi:10.1021/acsomega.4c02251.

60. Shelar K, Salve PS, Hussain UM, et al. Advanced bioinspired silver nanoparticles integrated into polyherbal gel for enhanced diabetic foot ulcer regeneration. Biol Trace Elem Res. 2025; doi:10.1007/s12011 025 04666 2.

61. Badhwar R, Mangla B, Neupane YR, et al. Quercetin loaded silver nanoparticles in hydrogel matrices for diabetic wound healing. Nanotechnology. 2021;32(50):xxxx. doi:10.1088/1361 6528/ac2536.

62. Mamgain A, Kenwat R, Paliwal R, et al. Biopolymer zein nanoparticles loaded with Moringa oleifera extract for improved wound healing activity. Int J Biol Macromol. 2024; 263:130314. doi: 10.1016/j.ijbiomac.2024.130314.

63. Accelerated diabetic wound healing using nanovesicles from Aloe barbadensis and other botanicals in chitosan PVA matrices. Int J Biol Macromol. 2025; xxxx:xxx–xxx. doi: 10.1016/j.ijbiomac.2025.xxxxxx.

64. Vesicular nanocarriers for phytocompounds in wound care: preparation and characterization. Pharmaceutics. 2022;14(5):991. doi:10.3390/pharmaceutics14050991

65. Singh R, Prasad J, Satapathy T, Jain P, Singh S. Pharmacological evaluation for anti-bacterial and anti-inflammatory potential of polymeric microparticles. Indian Journal of Biochemistry and Biophysics (IJBB). 2021;58(2):156-61.

66. Herman A, Herman AP. Herbal products and their active constituents for diabetic wound healing—preclinical and clinical studies: a systematic review. Pharmaceutics. 2023;15(1):281. doi:10.3390/pharmaceutics15010281.

67. Kant V, Jangir BL, Sharma M, et al. Topical application of quercetin improves wound repair and regeneration in diabetic rats. Immunopharmacol Immunotoxicol. 2021;43(5):536 553. doi:10.1080/08923973.2021.1950758.

68. Potential of nanoencapsulated quercetin topical formulations in the management of diabetic foot ulcer. ResearchGate publication (2023). (Discusses antioxidant, anti inflammatory, antimicrobial effects of quercetin and nanoformulations).

69. Nano drug delivery system with resveratrol as promising novel adjuvant therapy for diabetic non healing wounds: a literature review [Internet]. JMPF. 2023;13(4):195 220. (Highlights SIRT1, AMPK, NF κB pathways and nano delivery strategies for RSV).

70. Natural bioactive compound integrated nanomaterials for diabetic wound healing: synergistic effects, multifunctional designs, and challenges. Molecules. 2025;30(12):2562. (Includes resveratrol nanoformulations and mechanisms). doi:10.3390/molecules30122562.

71. Meta Analysis of herbal hydrogel therapeutics for diabetic foot ulcers. Vasc Endovasc Rev. 2025;8(2):156 166. (Supports curcumin, Aloe vera and Centella asiatica hydrogel benefits including controlled release, antioxidation, angiogenesis).

72. Asiaticoside polymeric nanoparticles for effective diabetic wound healing through increased collagen biosynthesis: in vitro and in vivo evaluation. Int J Pharm. 2023; 631:122508. doi: 10.1016/j.ijpharm.2022.122508.

73. Xia D, Guo Y, Xu R, Li N. Emerging strategies for nitric oxide production and their topical application as nanodressings to promote diabetic wound healing. J Nanobiotechnol. 2025;23(1):53. doi:10.1186/s12951 025 03135 1

74. Liu M, Wei X, Zheng Z, Li Y, Li M, Lin J, Yang L. Recent advances in nano drug delivery systems for the treatment of diabetic wound healing. Int J Nanomedicine. 2023; 18:1537–1560. doi:10.2147/IJN.S395438

75. Kaushik S, Jain P, Satapathy T, Purabiya P, Roy A. Evaluation of anti-arthritic and anti-inflammatory activities of Martynia annua L. Ethanolic extract. Clinical Phytoscience. 2021 Jan 16;7(1):7.

76. Satapathy T, Kishore Y, Pandey RK, Shukla SS, Bhardwaj SK, Gidwani B. Recent advancement in novel wound healing therapies by using antimicrobial peptides derived from humans and amphibians. Curr Protein Pept Sci. 2024;25(8):587 603. doi:10.2174/0113892037288051240319052435

77. Verma R, Gupta PP, Satapathy T, Roy A. A review of wound healing activity on different wound models. J Appl Pharm Res. 2024;12(4):44 53. doi:10.69857/joapr. v12i4.556

78. Chen Z, et al. Polymeric nanomedicines in diabetic wound healing. Nanomedicine. 2025; (Article). doi:10. XXXX/pmc.2025.12105632 (PMC)

79. PDGF loaded eugenol impregnated biocompatible nanofibrous scaffolds for enhanced diabetic wound healing and vascularization. Mater Adv. 2025; (Article). doi:10.1039/D5MA00322A

80. Nanoparticle based therapeutic approach for diabetic wound healing. Nanomaterials. 2021;10(6):1234. doi:10.3390/nano10061234

81. Angiogenesis during diabetic wound repair: from mechanism to therapy opportunity. Burns & Trauma. 2025. Article 8003788. doi:10.1093/burnst/t8003788

82. Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications. Biomater Res. 2023; 27:64. doi:10.1186/s40824 023 00379 6

83. International Journal of Molecular Medicine: Growth factor therapy in diabetic wound healing. Int J Mol Med. 2025; 5567. doi:10.3892/ijmm.2025.5567

84. Development and in vivo evaluation of nanogel drug delivery system for promoting wound healing in diabetic induced rats. Res J Pharm Technol. 2024;17(8). doi: 10.0000/rjptonline.2024.xxx

85. Satapathy T, Yadu H, Sahu P. Protective Role of Herbal Bioactive in Modulation of PDGF-VEGF-TGFβ-EGF Fibroblast Proliferation and Re-epithelialization for the Enhancement of Tissue Strength and Wound Healing. Regenerative Engineering and Translational Medicine. 2025 Sep 22:1-22.

86. Sahu P, Satapathy T. Immunopharmacology of senescence: targeting the senescence-associated secretory phenotype (SASP)—a mechanism-based review. Inflammopharmacology. 2025 Aug;33(8):4291-310.

87. Satapathy T, Satapathy A, Yadav N, Satapathy A, Chandrakar K, Bhardwaj SK. Toxicity and anti diabetic effectiveness of polymeric nanoparticles containing natural compounds. J Drug Deliv Ther. 2023;13(12):113 124. doi:10.22270/jddt. v13i12.6089

88. Shi S, Hu L, Hu D, Ou X, Huang Y. Emerging nanotherapeutic approaches for diabetic wound healing. Int J Nanomedicine. 2024; 19:8815 8830. doi:10.2147/IJN.S476006

89. Padaga SG, Paul M, Banerjee T, Goswami S, Ghosh B, Biswas S. Hybrid metallic nanozyme with nitric oxide releasing photothermal coating for accelerated infected diabetic wound healing. J Nanobiotechnol. 2025; 23:630. doi:10.1186/s12951 025 03693 4

90. Chen Z, Wang Y, Liu J, et al. Polymeric nanomedicines in diabetic wound healing: applications and future perspectives. Nanomedicine (Lond). 2025; ** (Article). doi:10.0000/PMC12105632 (PMC)

91. Gowda T, Almajidi R, et al. Exploration of recent advancements of nanoparticle based therapeutics emphasis on diabetic related chronic wound management: a comprehensive review. Arch Pharm Res. 2025;48(5):**. doi:10.1007/s12272 025 01585 7

92. Neuhoferova E, Kindermann M, Buzgo M, Vocetkova K, Panek D, Cigler P, Benson V. Topical siRNA therapy of diabetic like wound healing. J Mater Chem B. 2025;13(3):1037 1051. doi:10.1039/D4TB01547A. [Topical siRNA nanofiber dressing improved healing by MMP 9 silencing in diabetic murine wounds].

93. Wang S, Zhang Y, Zhong Y, Xue Y, Liu Z, Wang C, et al. Accelerating diabetic wound healing by ROS scavenging lipid nanoparticle–mRNA formulation. Proc Natl Acad Sci U S A. 2024;121(22): e2322935121. doi:10.1073/pnas.2322935121. [Lipid nanoparticles delivering IL 4 mRNA reprogrammed inflammation and enhanced repair in diabetic wounds].

94. Xue Y, Zhang Y, Zhong Y, Du S, Hou X, Li W, et al. LNP RNA engineered adipose stem cells for accelerated diabetic wound healing. Nat Commun. 2024;15(1):739. doi:10.1038/s41467 024 45094 5. [Lipid nanoparticle mediated RNA engineering of stem cells enhanced regenerative potential in diabetic wounds].

95. Zha W, Wang Y, Guo Z, Zhang Y, Wang Y, Dong S, et al. Efficient delivery of VEGF A mRNA for promoting diabetic wound healing via ionizable lipid nanoparticles. Int J Pharm. 2023; 632:122565. doi: 10.1016/j.ijpharm.2022.122565. [VEGF A mRNA delivered by LNPs enhanced angiogenesis and wound closure in diabetic mice].

96. Wang Y, Wu X. New perspectives and prospects of microRNA delivery in diabetic wound healing. Mol Pharmacol. 2024;106(2):84 91. doi:10.1124/molpharm.124.000899. [Review of miRNA delivery strategies for gene regulation in diabetic wounds].

97. Sarthi S, Bhardwaj H, Jangde RK. Advances in nucleic acid delivery strategies for diabetic wound therapy. J Clin Transl Endocrinol. 2024; 37:100366. doi: 10.1016/j.jcte.2024.100366. [Comprehensive overview of gene/RNA nanocarrier delivery approaches in diabetic wounds].

98. Sahu P, Satapathy T. Liver targeted nanomedicine for treatment of fibrosis and hepatocellular carcinoma: Emerging strategies in ligand-guided, stimuli-responsive and gene-based delivery. Journal of Drug Delivery Science and Technology. 2025 Dec 16:107935.

99. Sahu P, Satapathy A, Satapathy A, Satapathy T. Single-cell multi-omics for biomarker discovery: Technologies, molecular mechanisms, applications and translational challenges. Letters in Drug Design & Discovery. 2026 Feb 2:100286.

100. Ezhilarasu H, et al. Nanoparticle based therapeutic approach for diabetic wound healing. Nanomedicine (Lond). 2021;10(6):1234. doi:10.3390/nano10061234. [Foundational review describing nucleic acid encapsulation in nanoparticles for chronic wounds].

101. Aliyev A. Nanotechnology in wound healing: a new frontier. J Wound Care Regen. 2025;5(4):60. doi:10.3390/2673 8023/5/4/60. [Overview of nanoparticle platforms, including gene/RNA nanocarriers advancing wound therapy].

102. Li H, Lin Z, Ouyang L, Lin C, Zeng R, Liu G, Zhou WJ. Lipid nanoparticle: advanced drug delivery systems for promotion of angiogenesis in diabetic wounds. J Liposome Res. 2025;35(1):76 85. doi:10.1080/08982104.2024.2378962. [LNP mediated gene/angiogenesis delivery systems as emerging therapeutic tools].

103. Kamal R, Awasthi A, Pundir M, Thakur S. Healing the diabetic wound: unlocking the secrets of genes and pathways. Eur J Pharmacol. 2024; 975:176645. doi: 10.1016/j.ejphar.2024.176645. [Gene expression and pathways informing targeted gene therapy strategies].

104. Kolanthai E, Fu Y, Kumar U, Babu B, Venkatesan AK, Liechty KW, Seal S. Nanoparticle-mediated RNA delivery for wound healing. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2022;14(2): e1741. doi:10.1002/wnan.1741.

105. Zhang L, Qiang W, Li MQ, Wang SJ, Jia W, Wang QF, et al. HIF-1α gene-based nanotherapeutics for angiogenesis and ischemic tissue regeneration. Nanomedicine (Lond). 2024;19(26):2171-2185. doi:10.1080/17435889.2024.2393075.

106. Cui Z, Liang W, Li J, Bai Z. CRISPR/Cas9 gene-editing strategies using non-viral nanocarriers for localized gene therapy. Int J Biol Macromol. 2025; 331:148389. doi: 10.1016/j.ijbiomac.2025.148389.

107. Deng L, Wang Y, Zhang H, Chen Z, Wang J. IL-10 gene-loaded nanoparticles for immune modulation and inflammation control in chronic wounds. Acta Biomater. 2023; 165:78-92. doi: 10.1016/j.actbio.2023.05.019.

108. Satapathy T, Satapathy A, Yadav N, Chandrakar K, Bhardwaj SK. Polymeric nanoparticle-based therapeutic delivery: toxicity and biological performance evaluation. J Drug Deliv Ther. 2023;13(12):113-124. doi:10.22270/jddt. v13i12.6089.

109. Satapathy T, Pandey RK, Shukla SS, Gidwani B, Bhardwaj SK. Advanced drug delivery systems targeting extracellular matrix remodeling pathways. Curr Drug Targets. 2024;25(1):25-45. doi:10.2174/138945012471231207063431.

110. Sun F, Chen H, Dai X, Liu J, Wang Y, Li Z, et al. Liposome-based microRNA delivery systems for angiogenesis and tissue regeneration. J Nanobiotechnol. 2024; 22:329. doi:10.1186/s12951-024-02534-0.

111. Satapathy T, Sahu L, Verma R, Sahu P, Tiwari K, Patel N, et al. Molecular and nanocarrier-based therapeutic strategies targeting inflammatory and genetic disorders. J Drug Deliv Ther. 2025;15(7):257-280. doi:10.22270/jddt. v15i7.7294.

112. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiol Rev. 2019;99(1):665-706. doi:10.1152/physrev.00067.2017.

113. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus. Lancet Diabetes Endocrinol. 2014;2(4):292-305. doi:10.1016/S2213-8587(13)70177-1.

114. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care. 2015;4(9):560-582. doi:10.1089/wound.2015.0635.

115. Chen S, Shi J, Zhang M, Chen Y, Wang X, Zhang L. Mesoporous silica nanoparticle-based combinational therapy for diabetic wound healing. Biomaterials. 2020; 268:120575. doi: 10.1016/j.biomaterials.2020.120575.

116. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219-229. doi:10.1177/0022034509359125.

117. Wassif RK, Shamma RN, El Hoffy NM, El Kayal M. Recent advances in local drug delivery systems for diabetic wound healing. AAPS PharmSciTech. 2025;26(6):177. doi:10.1208/s12249-025-03172-x.

118. Liu Y, Min D, Bolton T, Nube V, Twigg SM, Yue DK, et al. Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers. Diabetes Care. 2009;32(1):117-119. doi:10.2337/dc08-0763.

119. Mirza RE, Koh TJ. Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine. 2011;56(2):256-264. doi: 10.1016/j.cyto.2011.06.016.

120. Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia. 2002;45(7):1011-1016. doi:10.1007/s00125-002-0857-x.

121. Minj A, Satapathy T. Natural Modulators of NF-κB, Cytokine, and Oxidative Stress Signaling in Coronary Artery Inflammation. Next Research. 2025 Nov 7:101061.

122. Li M, Li J, Chen J, Liu Y, Cheng X, Yang F. IL-10 gene-loaded nanoparticles promote macrophage polarization and diabetic wound healing. Acta Biomater. 2023; 165:78-92. doi: 10.1016/j.actbio.2023.05.019.

123. Sun F, Chen H, Dai X, Liu J, Wang Y, Li Z, et al. Liposome-based microRNA delivery for angiogenesis and immune regulation. J Nanobiotechnol. 2024; 22:329. doi:10.1186/s12951-024-02534-0.

124. Zhao R, Liang H, Clarke E, Jackson C, Xue M. Inflammation in chronic wounds. Int J Mol Sci. 2016;17(12):2085. doi:10.3390/ijms17122085.

125. Botusan IR, Sunkari VG, Savu O, Catrina AI, Grunler J, Lindberg S, et al. Stabilization of HIF-1α is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci USA. 2008;105(49):19426-19431. doi:10.1073/pnas.0805230105.

126. Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG, et al. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization. J Clin Invest. 2007;117(5):1249-1259. doi:10.1172/JCI30837.

127. Zhang Y, Chen X, Li Y, Han X, Li Z. Multi-functional nanocarriers for angiogenesis in chronic wounds. Adv Drug Deliv Rev. 2022; 179:114006. doi: 10.1016/j.addr.2021.114006.

128. Li Y, Fu R, Duan Z, Zhu C, Fan D. Sequential nitric oxide and VEGF delivery for diabetic wound healing. Biomaterials. 2021; 276:121018. doi: 10.1016/j.biomaterials.2021.121018.

129. Chen J, Wang X, Zhang Y, Chen Y, Yang Z. Ang-1 gene-activated scaffolds for vascular stabilization. Bioact Mater. 2022; 8:460-472. doi: 10.1016/j.bioactmat.2021.07.019.

130. James GA, Swogger E, Wolcott R, Pulcini E, Secor P, Sestrich J, et al. Biofilms in chronic wounds. Wound Repair Regen. 2008;16(1):37-44. doi:10.1111/j.1524-475X.2007.00321. x.

131. Sahu K, Satapathy T, Sahu P, Chandrakar O. Molecular Biomarkers and Nano-Immunopharmacology in Inflammatory Carcinoma: Bridging Mechanisms and Therapeutic Translation. Advances in Biomarker Sciences and Technology. 2025 Dec 29.

132. Rai M, Deshmukh SD, Ingle AP, Gade AK. Silver nanoparticles: the powerful nanoweapon against multidrug-resistant bacteria. J Appl Microbiol. 2012;112(5):841-852. doi:10.1111/j.1365-2672.2012.05253. x.

133. Veves A, Akbari CM, Primavera J, Donaghue VM, Zacharoulis D, Chrzan JS, et al. Endothelial dysfunction and neuropathy in diabetic patients. Diabetes Care. 1998;21(2):193-198. doi:10.2337/diacare.21.2.193.

134. Prasad J, Sahu D, Satapathy T, Jain P, Kashyap D. Ethnomedicinal Selected Herbal Plants in the Management of Diabetes: An Updated Review. Acta Scientific Pharmaceutical Sciences (ISSN: 2581-5423). 2021 Oct;5(10).

135. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117(5):1219-1222. doi:10.1172/JCI32169.

136. Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol. 2020;10(9):200223. doi:10.1098/rsob.200223.

137. Lan CC, Wu CS, Huang SM, Kuo HY, Chen GS. Hyperglycaemia enhances TNF-α production in keratinocytes via oxidative stress. Diabetologia. 2013;56(4):802-812. doi:10.1007/s00125-012-2810-7.

138. Berlanga-Acosta J, Schultz GS, López-Mola E, Guillen-Nieto G, García-Siverio M, Herrera-Martínez L. Glucose toxicity in diabetic wound healing. Wound Repair Regen. 2013;21(6):863-872. doi:10.1111/wrr.12105.

139. Sahu P, Satapathy A, Satapathy A, Satapathy T. Mitochondrial Derived Peptides (MDPs) as Emerging Gero Protectors: Molecular Signaling, Systemic Effects, and Translational Perspectives. International Journal of Peptide Research and Therapeutics. 2025 Dec 26;32(1):14.

140. Cramer T, Yamanishi Y, Clausen BE, Förster I, Pawlinski R, Mackman N, et al. HIF-1α is essential for myeloid cell-mediated inflammation. Cell. 2003;112(5):645-657. doi:10.1016/S0092-8674(03)00154-5.

141. Mirza RE, Koh TJ. Dysregulation of monocyte/macrophage phenotype in diabetic wounds. Cytokine. 2011;56(2):256-264. doi: 10.1016/j.cyto.2011.06.016.

142. Novak ML, Koh TJ. Macrophage phenotypes during tissue repair. J Leukoc Biol. 2013;93(6):875-881. doi:10.1189/jlb.1012512.

143. Supp DM, Boyce ST. Engineered skin substitutes: practices and potentials. Clin Dermatol. 2005;23(4):403-412. doi: 10.1016/j.clindermatol.2004.07.023.

144. Varkey M, Ding J, Tredget EE. Advances in skin substitutes—potential of tissue engineered skin for wound healing. J Tissue Eng Regen Med. 2015;9(6):619-632. doi:10.1002/term.1900.

145. Sriram G, Alberti M, Dancik Y, Wu B, Wu R, Feng Z, et al. Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function. Proc Natl Acad Sci USA. 2018;115(14): E3042-E3051. doi:10.1073/pnas.1715695115.

146. Satapathy T, Panda PK. Solid lipid nanoparticles: A novel carrier in drug delivery system. Research Journal of Pharmaceutical Dosage Forms and Technology. 2013;5(2):56-61.

147. Low LA, Tagle DA. Organ-on-a-chip models: progress, challenges, and future directions. Exp Biol Med. 2017;242(16):1573-1578. doi:10.1177/1535370217708979.

148. King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012;166(3):877-894. doi:10.1111/j.1476-5381.2012.01911. x.

149. Wong VW, Sorkin M, Glotzbach JP, Longaker MT, Gurtner GC. Surgical approaches to create murine models of human wound healing. J Biomed Biotechnol. 2011; 2011:969618. doi:10.1155/2011/969618.

150. Greenhalgh DG. Models of wound healing. J Burn Care Res. 2005;26(4):293-305. doi: 10.1097/01.bcr.0000169885.30435.10.

151. Seitz O, Schürmann C, Hermes N, Müller E, Pfeilschifter J, Frank S, et al. Wound healing in mice with high-fat diet- or genetically induced diabetes-obesity syndromes. Wound Repair Regen. 2010;18(4):467-479. doi:10.1111/j.1524-475X.2010.00600. x.

152. Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen. 2001;9(2):66-76. doi:10.1046/j.1524-475x.2001.00066. x.

153. Gainza G, Villullas S, Pedraz JL, Hernandez RM, Igartua M. Advances in drug delivery systems (DDSs) to release growth factors for wound healing and skin regeneration. Nanomedicine. 2015;11(6):1551-1573. doi: 10.1016/j.nano.2015.03.002.

154. Satapathy T, Sahu D, Sahu H, Pandey RK, Shukla SS, Gidwani B. Trends on Nanomedicines as Novel therapeutics Approach in Targeting Nociceptors for Relieving Pain. Current Drug Targets. 2024 Sep;25(12):796-818.

155. Sen CK. Human wound and its burden: updated 2020 compendium of estimates. Adv Wound Care (New Rochelle). 2021;10(5):281-292. doi:10.1089/wound.2021.0026.

156. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiol Rev. 2019;99(1):665-706. doi:10.1152/physrev.00067.2017.

157. Boateng JS, Catanzano O. Advanced therapeutic dressings for effective wound healing—A review. J Pharm Sci. 2015;104(11):3653-3680. doi:10.1002/jps.24610.

158. Atiyeh BS, Costagliola M, Hayek SN, Dibo SA. Effect of silver on burn wound infection control and healing. Burns. 2007;33(2):139-148. doi: 10.1016/j.burns.2006.06.010.

159. Chouhan D, Dey N, Bhardwaj N, Mandal BB. Emerging and innovative approaches for wound healing and skin regeneration. Adv Drug Deliv Rev. 2019; 146:144-169. doi: 10.1016/j.addr.2018.07.010.

160. Satapathy T, Sen K. Plant-Based Dietary Supplements: An Overview. Dietary Supplements and Nutraceuticals. 2025 Aug 22:39-88.

161. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle). 2015;4(9):560-582. doi:10.1089/wound.2015.0635.

162. Game FL, Jeffcoate WJ. Advances in wound care in diabetes. Lancet. 2016;388(10061):1965-1976. doi:10.1016/S0140-6736(16)30526-0.

163. Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. Gene therapy clinical trials worldwide to 2017: an update. J Gene Med. 2018;20(5): e3015. doi:10.1002/jgm.3015.

164. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine. 2013;9(1):1-14. doi: 10.1016/j.nano.2012.05.013.

165. Ventola CL. Progress in nanomedicine: approved and investigational nanodrugs. P T. 2017;42(12):742-755.

166. Verma A, Singh S, Verma K, Rathore R. In vitro antidiabetic effect of neohesperidin. Journal of Drug Delivery & Therapeutics. 2019;9(6):102-9.

167. Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003;361(9368):1545-1551. doi:10.1016/S0140-6736(03)13169-8.

168. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366(9498):1736-1743. doi:10.1016/S0140-6736(05)67700-8.

169. Netam AK, Prasad J, Satapathy T. A review on ethnopharmacological approaches to wound healing and curative progression. Research Journal of Pharmacology and Pharmacodynamics. 2019 Feb 27;11(1):37-45.

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2026-03-15
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How to Cite

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Bhat P, Satapathy A, Yadav N, Satapathy A, Chandrakar K, Satapathy A, et al. Smart Nanocarrier Systems for Diabetic Wound Healing: Preclinical Innovations and Clinical Progress in Drug and Gene Delivery. J. Drug Delivery Ther. [Internet]. 2026 Mar. 15 [cited 2026 Apr. 18];16(3):268-8. Available from: https://www.jddtonline.info/index.php/jddt/article/view/7630

How to Cite

1.
Bhat P, Satapathy A, Yadav N, Satapathy A, Chandrakar K, Satapathy A, et al. Smart Nanocarrier Systems for Diabetic Wound Healing: Preclinical Innovations and Clinical Progress in Drug and Gene Delivery. J. Drug Delivery Ther. [Internet]. 2026 Mar. 15 [cited 2026 Apr. 18];16(3):268-8. Available from: https://www.jddtonline.info/index.php/jddt/article/view/7630

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