Skip to content
2000
image of Novel Approaches in Targeted Drug Delivery for Treatment of Neuropathy

Abstract

Neuropathy, a devastating disorder of the peripheral nervous system, results in pain, numbness, and weakness, profoundly impacting quality of life. Conventional therapies provide insufficient alleviation, requiring targeted drug delivery systems (TDDS) to improve effectiveness and reduce adverse effects. This review examines diverse TDDS methodologies, encompassing intrathecal therapy, radiofrequency ablation, and spinal cord stimulation, in conjunction with innovations in nanotechnology-driven delivery systems. Nanotechnology offers a novel framework for neuropathy treatment, including nanomaterials such as dendrimers, micelles, polymer nanoparticles, liposomes, hydrogels, and quantum dots. These carriers enhance drug encapsulation, cellular absorption, and sustained release, thereby improving therapeutic efficacy and minimizing systemic toxicity. Gene therapy presents a promising approach, targeting the modulation of neuropathic pathways and facilitating neuron regeneration. Although it remains in preliminary research stages, it holds potential for future therapies, especially in diabetic neuropathy. Moreover, transdermal drug delivery offers a non-invasive method to deliver drugs directly to targeted regions, enhancing bioavailability and patient adherence. The integration of nanotechnology, gene therapy, and transdermal administration has the potential to transform neuropathy treatment by providing more accurate and effective medicines. A multidisciplinary approach is essential to fully exploit the promise of TDDS and improve care and quality of life for patients with neuropathy.

Loading

Article metrics loading...

/content/journals/raddf/10.2174/0126673878372806251128113526
2026-01-21
2026-02-03
Loading full text...

Full text loading...

References

  1. Javaid M. Haleem A. Singh R.P. Suman R. Sustaining the healthcare systems through the conceptual of biomedical engineering: A study with recent and future potentials. Biomedical Technology 2023 1 39 47 10.1016/j.bmt.2022.11.004
    [Google Scholar]
  2. Tewabe A. Abate A. Tamrie M. Seyfu A. Abdela Siraj E. Targeted drug delivery — from magic bullet to nanomedicine: Principles, challenges, and future perspectives. J. Multidiscip. Healthc. 2021 14 1711 1724 10.2147/JMDH.S313968 34267523
    [Google Scholar]
  3. Baryakova T.H. Pogostin B.H. Langer R. McHugh K.J. Overcoming barriers to patient adherence: The case for developing innovative drug delivery systems. Nat. Rev. Drug Discov. 2023 22 5 387 409 10.1038/s41573‑023‑00670‑0 36973491
    [Google Scholar]
  4. Jeong S.H. Jang J.H. Lee Y.B. Drug delivery to the brain via the nasal route of administration: Exploration of key targets and major consideration factors. J. Pharm. Investig. 2023 53 1 119 152 10.1007/s40005‑022‑00589‑5 35910081
    [Google Scholar]
  5. De Souza J.M. Trevisan T.J. Sepresse S.R. Londe A.C. França Júnior M.C. Appenzeller S. Peripheral neuropathy in systemic autoimmune rheumatic diseases—diagnosis and treatment. Pharmaceuticals 2023 16 4 587 10.3390/ph16040587 37111344
    [Google Scholar]
  6. Gu J. Lu H. Chen C. Diabetes mellitus as a risk factor for chemotherapy-induced peripheral neuropathy: A meta-analysis. Support. Care Cancer 2021 29 12 7461 7469 10.1007/s00520‑021‑06321‑7 34085148
    [Google Scholar]
  7. Pop-Busui R. Ang L. Boulton A. Diagnosis and treatment of painful diabetic peripheral neuropathy. ADA Clinical Compendia 2022 2022 1 1 32 10.2337/db2022‑01 35544662
    [Google Scholar]
  8. Zhuo Y. Zhao Y.G. Zhang Y. Enhancing drug solubility, bioavailability, and targeted therapeutic applications through magnetic nanoparticles. Molecules 2024 29 20 4854 10.3390/molecules29204854 39459222
    [Google Scholar]
  9. Li J. Wang Q. Xia G. Recent advances in targeted drug delivery strategy for enhancing oncotherapy. Pharmaceutics 2023 15 9 2233 10.3390/pharmaceutics15092233 37765202
    [Google Scholar]
  10. Xu Y. Dong X. Xu H. Jiao P. Zhao L.X. Su G. Nanomaterial-based drug delivery systems for pain treatment and relief: From the delivery of a single drug to co-delivery of multiple therapeutics. Pharmaceutics 2023 15 9 2309 10.3390/pharmaceutics15092309 37765278
    [Google Scholar]
  11. Rafati N. Zarepour A. Bigham A. Nanosystems for targeted drug delivery: Innovations and challenges in overcoming the blood-brain barrier for neurodegenerative disease and cancer therapy. Int. J. Pharm. 2024 666 124800 10.1016/j.ijpharm.2024.124800 39374818
    [Google Scholar]
  12. Rodríguez-Sánchez B. Sinclair A. Health economics of diabetic foot disease: Costs of diabetic neuropathy and diabetic foot. Diabetic Neuropathy. Elsevier 2022 211 221 10.1016/B978‑0‑12‑820669‑0.00017‑7
    [Google Scholar]
  13. He F. Gu X-S. Chu X-L. Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation. Neural Regen. Res. 2022 17 10 2185 2193 10.4103/1673‑5374.335823 35259827
    [Google Scholar]
  14. Hange N. Poudel S. Ozair S. Managing chronic neuropathic pain: Recent advances and new challenges. Neurol. Res. Int. 2022 2022 1 14 10.1155/2022/8336561 36277331
    [Google Scholar]
  15. Ezike T.C. Okpala U.S. Onoja U.L. Advances in drug delivery systems, challenges and future directions. Heliyon 2023 9 6 e17488 10.1016/j.heliyon.2023.e17488 37416680
    [Google Scholar]
  16. Shah N. Di Napoli R. Padalia D. Implantable intrathecal drug delivery system. StatPearls 2024 www.ncbi.nlm.nih.gov/books/NBK538237/
    [Google Scholar]
  17. Ellis D.J. Dissanayake S. McGuire D. Continuous intrathecal infusion of ziconotide for treatment of chronic malignant and nonmalignant pain over 12 months: A prospective, open-label study. Neuromodulation 2008 11 1 40 49 10.1111/j.1525‑1403.2007.00141.x 22150990
    [Google Scholar]
  18. Li Y. Ji R.R. Gene therapy for chronic pain management. Cell Rep. Med. 2024 5 10 101756 10.1016/j.xcrm.2024.101756 39366385
    [Google Scholar]
  19. Kapural L. Deering J. Spinal cord stimulation. Regional Nerve Blocks in Anesthesia and Pain Therapy 2023 927 935 10.1007/978‑3‑030‑88727‑8_72
    [Google Scholar]
  20. Chapman K.B. Tupper C. Yang A. van Helmond N. Yousef T. Intermittent dorsal root ganglion stimulation is as efficacious as standard continuous dosing in treating chronic pain: results from a randomized controlled feasibility trial. Neuromodulation 2022 25 7 989 997 10.1016/j.neurom.2021.10.008 35088752
    [Google Scholar]
  21. Yang Y. Zhao B. Wang Y. Diabetic neuropathy: Cutting-edge research and future directions. Signal Transduct. Target. Ther. 2025 10 1 132 10.1038/s41392‑025‑02175‑1 40274830
    [Google Scholar]
  22. Wray J.K. Dixon B. Przkora R. Radiofrequency ablation. Innovations in Gastrointestinal Endoscopy. Springer 2023 207 215 10.1007/978‑981‑15‑9247‑8_16
    [Google Scholar]
  23. Eskandar E. Kumar H. Boini A. The role of radiofrequency ablation in the treatment of trigeminal neuralgia: A narrative review. Cureus 2023 15 3 e36193 10.7759/cureus.36193 37065382
    [Google Scholar]
  24. Wong W.F. Ang K.P. Sethi G. Looi C.Y. Recent advancement of medical patch for transdermal drug delivery. Medicina 2023 59 4 778 10.3390/medicina59040778 37109736
    [Google Scholar]
  25. Sen O. Poddar P. Sarkar P. Das S. Manna S. Current advancements in microneedle technology for therapeutic and biomedical applications. Sens Int 2025 6 100325 10.1016/j.sintl.2024.100325
    [Google Scholar]
  26. Liu Y. Mao R. Han S. Yu Z. Xu B. Xu T. Polymeric microneedle drug delivery systems: Mechanisms of treatment, material properties, and clinical applications—A comprehensive review. Polymers 2024 16 18 2568 10.3390/polym16182568 39339032
    [Google Scholar]
  27. Martins J.P. Marson F.A.L. A narrative review of the complex panorama regarding chronic neuropathic pain mainly for the psychological issues. Heliyon 2024 10 19 e38282 10.1016/j.heliyon.2024.e38282 39403499
    [Google Scholar]
  28. Adeli F. Abbasi F. Ghandforoushan P. Recent advances in formulation and application of molecular polymer brushes in biomedicine: Therapeutic, diagnostic, and theranostics capabilities. Nano Today 2023 53 102010 10.1016/j.nantod.2023.102010
    [Google Scholar]
  29. Asimakidou E. Tan J.K.S. Zeng J. Lo C.H. Blood–brain barrier-targeting nanoparticles: Biomaterial properties and biomedical applications in translational neuroscience. Pharmaceuticals 2024 17 5 612 10.3390/ph17050612 38794182
    [Google Scholar]
  30. Albayati N. Talluri S.R. Dholaria N. Michniak-Kohn B. AI-driven innovation in skin kinetics for transdermal drug delivery: Overcoming barriers and enhancing precision. Pharmaceutics 2025 17 2 188 10.3390/pharmaceutics17020188 40006555
    [Google Scholar]
  31. Madadi A.K. Sohn M.J. Advances in intrathecal nanoparticle delivery: Targeting the blood–cerebrospinal fluid barrier for enhanced CNS drug delivery. Pharmaceuticals 2024 17 8 1070 10.3390/ph17081070 39204177
    [Google Scholar]
  32. Jorge D de MF. Huber S.C. Rodrigues B.L. Da Fonseca L.F. Azzini G.O.M. Parada C.A. The mechanism of action between pulsed radiofrequency and orthobiologics: Is there a synergistic effect? Int. J. Mol. Sci. 2022 23 19 11726 10.3390/ijms231911726 36233026
    [Google Scholar]
  33. Park D. Chang M.C. The mechanism of action of pulsed radiofrequency in reducing pain: A narrative review. J Yeungnam Med Sci 2022 39 3 200 205 10.12701/jyms.2022.00101 35385898
    [Google Scholar]
  34. Li X. Peng X. Zoulikha M. Multifunctional nanoparticle-mediated combining therapy for human diseases. Signal Transduct. Target. Ther. 2024 9 1 1 33 10.1038/s41392‑023‑01668‑1 38161204
    [Google Scholar]
  35. Partridge B. Eardley A. Morales B.E. Advancements in drug delivery methods for the treatment of brain disease. Front. Vet. Sci. 2022 9 1039745 10.3389/fvets.2022.1039745 36330152
    [Google Scholar]
  36. Eckermann J.M. Pilitsis J.G. Vannaboutathong C. Wagner B.J. Province-Azalde R. Bendel M.A. Systematic literature review of spinal cord stimulation in patients with chronic back pain without prior spine surgery. Neuromodulation 2022 25 5 648 656 10.1111/ner.13519 34407288
    [Google Scholar]
  37. Zhitny V.P. Jannoud R. Young J.P. Radiofrequency ablation: Honoring the pioneers of modern therapeutic innovations. Cureus 2024 16 11 e72831 10.7759/cureus.72831 39618755
    [Google Scholar]
  38. Alkilani A.Z. Nasereddin J. Hamed R. Nimrawi S. Hussein G. Abo-Zour H. Beneath the skin: A review of current trends and future prospects of transdermal drug delivery systems. Pharmaceutics 2022 14 6 1152 10.3390/pharmaceutics14061152 35745725
    [Google Scholar]
  39. Kumbhar P.R. Kumar P. Lasure A. Velayutham R. Mandal D. An updated landscape on nanotechnology-based drug delivery, immunotherapy, vaccinations, imaging, and biomarker detections for cancers: Recent trends and future directions with clinical success. Discover Nano 2023 18 1 156 10.1186/s11671‑023‑03913‑6 38112935
    [Google Scholar]
  40. Wang J.H. Gessler D.J. Zhan W. Gallagher T.L. Gao G. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Signal Transduct. Target. Ther. 2024 9 1 78 10.1038/s41392‑024‑01780‑w 38565561
    [Google Scholar]
  41. Devi S. Kumar M. Tiwari A. Quantum dots: An emerging approach for cancer therapy. Front. Mater. 2022 8 798440 10.3389/fmats.2021.798440
    [Google Scholar]
  42. Oliveira C. Teixeira J.A. Oliveira N. Ferreira S. Botelho C.M. Microneedles’ device: Design, fabrication, and applications. Macromol 2024 4 320 355 10.3390/macromol4020019
    [Google Scholar]
  43. Kulkarni S. Prabhakar B. Shende P. Stabilization of lipid vesicles: Upcoming strategic insights for product development. J. Mol. Liq. 2022 348 118430 10.1016/j.molliq.2021.118430
    [Google Scholar]
  44. Wang S. Chen Y. Guo J. Huang Q. Liposomes for tumor targeted therapy: A review. Int. J. Mol. Sci. 2023 24 3 2643 10.3390/ijms24032643 36768966
    [Google Scholar]
  45. Qiu C Xia F Zhang J Shi Q Meng Y Wang C Advanced strategies for overcoming endosomal/lysosomal barrier in nanodrug delivery. Research 2023 6 0148 10.34133/research.0148 37250954
    [Google Scholar]
  46. Cunha J. Latocheski E. Fidalgo A.C.D. Gerola A.P. Marin C.F.F. Ribeiro A.J. Core-shell hybrid liposomes: Transforming imaging diagnostics and therapeutic strategies. Colloids Surf. B Biointerfaces 2025 251 114597 10.1016/j.colsurfb.2025.114597 40043539
    [Google Scholar]
  47. Fiorillo B.P. Melton M.S. Nelsen D. Einhorn L.M. Admixture of liposomal bupivacaine and bupivacaine hydrochloride for peripheral nerve blocks in adolescents undergoing orthopedic surgery: An observational cohort study. J. Clin. Med. 2024 13 24 7586 10.3390/jcm13247586 39768510
    [Google Scholar]
  48. Lv Y. Li W. Liao W. Nano-drug delivery systems based on natural products. Int. J. Nanomedicine 2024 19 541 569 10.2147/IJN.S443692 38260243
    [Google Scholar]
  49. Chowdhury S. Toth I. Stephenson R.J. Dendrimers in vaccine delivery: Recent progress and advances. Biomaterials 2022 280 121303 10.1016/j.biomaterials.2021.121303 34871877
    [Google Scholar]
  50. Graham W. Torbett-Dougherty M. Islam A. Soleimani S. Bruce-Tagoe T.A. Johnson J.A. Magnetic Nanoparticles and Drug Delivery Systems for Anti-Cancer Applications: A Review. Nanomaterials 2025 15 4 285 10.3390/nano15040285 39997849
    [Google Scholar]
  51. Jorgie A. Dutu A.G. Sovrea A. Constantin A.M. Samasca G. Masalar A.L. Nanocarriers for drug delivery: An overview with emphasis on vitamin D and K transportation. Nanomaterials 2022 12 1376 10.3390/nano12081376
    [Google Scholar]
  52. Wang J. Li B. Qiu L. Qiao X. Yang H. Dendrimer-based drug delivery systems: History, challenges, and latest developments. J. Biol. Eng. 2022 16 1 18 10.1186/s13036‑022‑00298‑5 35879774
    [Google Scholar]
  53. Yang J. Zeng H. Luo Y. Recent applications of PLGA in drug delivery systems. Polymers 2024 16 18 2606 10.3390/polym16182606 39339068
    [Google Scholar]
  54. van den Berg A.I.S. Yun C.O. Schiffelers R.M. Hennink W.E. Polymeric delivery systems for nucleic acid therapeutics: Approaching the clinic. J. Control. Release 2021 331 121 141 10.1016/j.jconrel.2021.01.014 33453339
    [Google Scholar]
  55. Lim Y.W. Tan W.S. Ho K.L. Challenges and complications of poly(lactic- co -glycolic acid)-based long-acting drug product development. Pharmaceutics 2022 14 3 614 10.3390/pharmaceutics14030614 35335988
    [Google Scholar]
  56. Khalbas A.H. Albayati T.M. Saady N.M.C. Zendehboudi S. Salih I.K. Tofah M.L. Insights into drug loading techniques with mesoporous silica nanoparticles: Optimization of operating conditions and assessment of drug stability. J. Drug Deliv. Sci. Technol. 2024 96 105698 10.1016/j.jddst.2024.105698
    [Google Scholar]
  57. Islam S. Ahmed M.M.S. Islam M.A. Hossain N. Chowdhury M.A. Advances in nanoparticles in targeted drug delivery–A review. Results Surf Interfaces 2025 19 100529 10.1016/j.rsurfi.2025.100529
    [Google Scholar]
  58. Liu B. Liu W. Xu M. Drug delivery systems based on mesoporous silica nanoparticles for the management of hepatic diseases. Acta Pharm. Sin. B 2025 15 2 809 833 10.1016/j.apsb.2024.12.015 40177563
    [Google Scholar]
  59. MacCuaig W.M. Samykutty A. Foote J. Toxicity assessment of mesoporous silica nanoparticles upon intravenous injection in mice: Implications for drug delivery. Pharmaceutics 2022 14 5 969 10.3390/pharmaceutics14050969 35631554
    [Google Scholar]
  60. Montanarella F. Kovalenko M.V. Three millennia of nanocrystals. ACS Nano 2022 16 4 5085 5102 10.1021/acsnano.1c11159 35325541
    [Google Scholar]
  61. Brondi M. Bruzzone M. Lodovichi C. dal Maschio M. Optogenetic methods to investigate brain alterations in preclinical models. Cells 2022 11 11 1848 10.3390/cells11111848 35681542
    [Google Scholar]
  62. Al-Thani A.N. Jan A.G. Abbas M. Geetha M. Sadasivuni K.K. Nanoparticles in cancer theragnostic and drug delivery: A comprehensive review. Life Sci. 2024 352 122899 10.1016/j.lfs.2024.122899 38992574
    [Google Scholar]
  63. Lin X. Chen T. A review of in vivo toxicity of quantum dots in animal models. Int. J. Nanomedicine 2023 18 8143 8168 10.2147/IJN.S434842 38170122
    [Google Scholar]
  64. Thang N.H. Chien T.B. Cuong D.X. Polymer-based hydrogels applied in drug delivery: An overview. Gels 2023 9 7 523 10.3390/gels9070523 37504402
    [Google Scholar]
  65. Nageshwar Dimple Patel Arun, Patel Shailendra, Ahirwar Vijay Pratap. A review article on hydrogel in drug delivery: A transformative approach. EPRA Int J Res Dev 2024 9 10.36713/epra2016
    [Google Scholar]
  66. Wang R. Cheng C. Wang H. Wang D. Swollen hydrogel nanotechnology: Advanced applications of the rudimentary swelling properties of hydrogels. ChemPhysMater 2024 3 4 357 375 10.1016/j.chphma.2024.07.006
    [Google Scholar]
  67. Gade L. Boyd B.J. Malmsten M. Heinz A. Stimuli-responsive drug delivery systems for inflammatory skin conditions. Acta Biomater. 2024 187 1 19 10.1016/j.actbio.2024.08.037 39209132
    [Google Scholar]
  68. Pablos J.L. Lozano D. Manzano M. Vallet-Regí M. Regenerative medicine: Hydrogels and mesoporous silica nanoparticles. Mater. Today Bio 2024 29 101342 10.1016/j.mtbio.2024.101342 39649249
    [Google Scholar]
  69. Omidian H. Chowdhury S.D. Cubeddu L.X. Hydrogels for neural regeneration: Exploring new horizons. Material 2024 17 14 3472 10.3390/ma17143472 39063768
    [Google Scholar]
  70. Lin X. Zhang X. Wang Y. Chen W. Zhu Z. Wang S. Hydrogels and hydrogel-based drug delivery systems for promoting refractory wound healing: Applications and prospects. Int. J. Biol. Macromol. 2025 285 138098 10.1016/j.ijbiomac.2024.138098 39608543
    [Google Scholar]
  71. Sultana A. Zare M. Thomas V. Kumar T.S.S. Ramakrishna S. Nano-based drug delivery systems: Conventional drug delivery routes, recent developments and future prospects. Med Drug Discov 2022 15 100134 10.1016/j.medidd.2022.100134
    [Google Scholar]
  72. Majumder J. Minko T. Multifunctional and stimuli-responsive nanocarriers for targeted therapeutic delivery. Expert Opin. Drug Deliv. 2021 18 2 205 227 10.1080/17425247.2021.1828339 32969740
    [Google Scholar]
  73. Kim D. Kim K.R. Kwon Y. AAV-mediated combination gene therapy for neuropathic pain: GAD65, GDNF, and IL-10. Mol. Ther. Methods Clin. Dev. 2020 18 473 483 10.1016/j.omtm.2020.06.018 32728596
    [Google Scholar]
  74. Kataria S. Patel U. Yabut K. Recent advances in management of neuropathic, nociceptive, and chronic pain: A narrative review with focus on nanomedicine, gene therapy, stem cell therapy, and newer therapeutic options. Curr. Pain Headache Rep. 2024 28 5 321 333 10.1007/s11916‑024‑01227‑5 38386244
    [Google Scholar]
  75. Artusi S. Miyagawa Y. Goins W.F. Cohen J.B. Glorioso J.C. Herpes simplex virus vectors for gene transfer to the central nervous system. Dis 2018 6 74 10.3390/diseases6030074
    [Google Scholar]
  76. Feldman E.L. Callaghan B.C. Pop-Busui R. Diabetic neuropathy. Nat. Rev. Dis. Primers 2019 5 1 41 10.1038/s41572‑019‑0092‑1 31197183
    [Google Scholar]
  77. Kawanaka R. Jin H. Aoe T. Unraveling the connection: Pain and endoplasmic reticulum stress. Int. J. Mol. Sci. 2024 25 4995 10.3390/ijms25094995
    [Google Scholar]
  78. Bodman M.A. Dreyer M.A. Varacallo M.A. Diabetic peripheral neuropathy. In: The Diabetes Textbook: Clinical Principles. 2nd ed. Springer 2024 923 37 10.1007/978‑3‑031‑25519‑9_56
    [Google Scholar]
  79. Zhu J. Hu Z. Luo Y. Diabetic peripheral neuropathy: Pathogenetic mechanisms and treatment. Front. Endocrinol. 2024 14 1265372 10.3389/fendo.2023.1265372 38264279
    [Google Scholar]
  80. Shen Y. Zhang H. Xue M. Zheng C. Chen Q. HSV-1 as a gene delivery platform for cancer gene therapy. Trends Pharmacol. Sci. 2025 46 4 324 336 10.1016/j.tips.2025.02.006 40069043
    [Google Scholar]
  81. Le Hars M. Joussain C. Jégu T. Epstein A.L. Non-replicative herpes simplex virus genomic and amplicon vectors for gene therapy - An update. Gene Ther. 2024 2024 1 11 10.1038/s41434‑024‑00500‑x 39533042
    [Google Scholar]
  82. Wolfe D. Goss J. Krisky D. Wechuck J. Herpes simplex virus-based nerve targeting gene therapy in pain management. J. Pain Res. 2014 7 71 79 10.2147/JPR.S36619 24470772
    [Google Scholar]
  83. Milani D.A.Q. Davis D.D. Pain management medications. StatPearls 2023 https://www.ncbi.nlm.nih.gov/books/NBK560692/
    [Google Scholar]
  84. García-Domínguez M. Enkephalins and pain modulation: Mechanisms of action and therapeutic perspectives. Biomolecules 2024 14 8 926 10.3390/biom14080926 39199314
    [Google Scholar]
  85. Dhaliwal A. Gupta M. Physiology, opioid receptor. StatPearls 2023 https://www.ncbi.nlm.nih.gov/books/NBK546642/
    [Google Scholar]
  86. Hirotsugu K. Shue L. Megumi K. Gene therapy with HSV encoding p55TNFR gene for HIV neuropathic pain: An evidence-based mini-review. Transl. Perioper. Pain Med. 2017 4 4 10.31480/2330‑4871/061
    [Google Scholar]
  87. Jewett B.E. Sharma S. Physiology, GABA. StatPearls 2023 https://www.ncbi.nlm.nih.gov/books/NBK513311/
    [Google Scholar]
  88. Ghoniem G. Khater U. Interstitial cystitis/bladder pain syndrome. Practical Guide to Female Pelvic Medicine. StatePearls 2024 239 249 10.1201/b14471‑22
    [Google Scholar]
  89. Salauddin M. Saha S. Hossain M.G. Okuda K. Shimada M. Clinical application of adenovirus (AdV): A comprehensive review. Viruses 2024 16 7 1094 10.3390/v16071094 39066256
    [Google Scholar]
  90. Muravyeva A. Smirnikhina S. Strategies for modifying adenoviral vectors for gene therapy. Int. J. Mol. Sci. 2024 25 12461 10.3390/ijms252212461
    [Google Scholar]
  91. Qian X. Zhao X. Yu L. Current status of GABA receptor subtypes in analgesia. Biomed. Pharmacother. 2023 168 115800 10.1016/j.biopha.2023.115800 37935070
    [Google Scholar]
  92. Takahashi K. Foster J.B. Lin C.L.G. Glutamate transporter EAAT2: Regulation, function, and potential as a therapeutic target for neurological and psychiatric disease. Cell. Mol. Life Sci. 2015 72 18 3489 3506 10.1007/s00018‑015‑1937‑8 26033496
    [Google Scholar]
  93. Herman T.F. Cascella M. Muzio M.R. Mu receptors. StatPearls 2024 https://www.ncbi.nlm.nih.gov/books/NBK551554/
    [Google Scholar]
  94. Hadi M. Qutaiba B. Allela O. Recent advances in various adeno-associated viruses (AAVs) as gene therapy agents in hepatocellular carcinoma. Virol. J. 2024 21 1 22 10.1186/s12985‑024‑02286‑1
    [Google Scholar]
  95. Moreno A.M. Alemán F. Catroli G.F. Long-lasting analgesia via targeted in situ repression of Na V 1.7 in mice. Sci. Transl. Med. 2021 13 584 eaay9056 10.1126/scitranslmed.aay9056 33692134
    [Google Scholar]
  96. Enna S.J. Sharma S. GABA receptors. Trends Pharmacol. Sci. 1981 2 62 64 10.1016/0165‑6147(81)90264‑9
    [Google Scholar]
  97. Chang H. Lee K.J. Park M. Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1. Neurotherapeutics 2025 22 2 e00511 10.1016/j.neurot.2024.e00511 39674763
    [Google Scholar]
  98. Islam A. Tom V.J. The use of viral vectors to promote repair after spinal cord injury. Exp. Neurol. 2022 354 114102 10.1016/j.expneurol.2022.114102 35513025
    [Google Scholar]
  99. Ledri M. Sørensen A.T. Kokaia M. Woldbye D.P.D. Gøtzsche C.R. Editorial: Gene therapy in the CNS – progress and prospects for novel therapies. Front. Mol. Neurosci. 2021 14 778134 10.3389/fnmol.2021.778134 34744628
    [Google Scholar]
  100. Wang Y. Shao W. Innate immune response to viral vectors in gene therapy. Viruses 2023 15 9 1801 10.3390/v15091801 37766208
    [Google Scholar]
  101. Park J. Farmer M. Casson C. Kalashnikova I. Kolpek D. Therapeutic potential of combinative shrna-encoded lentivirus-mediated gene silencing to accelerate somatosensory recovery after spinal cord trauma. Neurotherapeutics 2023 20 2 564 577 10.1007/s13311‑022‑01331‑7 36401079
    [Google Scholar]
  102. Li J. Yang K. Yao F. Wei H. Lentivirus-mediated RNA interference targeting HMGB1 modulates AQP1 to reduce pain induced by chronic compression of the dorsal root ganglia. Front. Pharmacol. 2024 15 1469223 10.3389/fphar.2024.1469223 39359252
    [Google Scholar]
  103. Li L. Chen J. Li Y.Q. The downregulation of opioid receptors and neuropathic pain. Int. J. Mol. Sci. 2023 24 6 5981 10.3390/ijms24065981 36983055
    [Google Scholar]
  104. Wang C. Pan C. Yong H. Emerging non-viral vectors for gene delivery. J. Nanobiotechnology 2023 21 1 272 10.1186/s12951‑023‑02044‑5 37592351
    [Google Scholar]
  105. Ren S. Wang M. Wang C. Application of non-viral vectors in drug delivery and gene therapy. Polymers 2021 13 19 3307 10.3390/polym13193307 34641123
    [Google Scholar]
  106. Hosseinkhani H. Domb A.J. Sharifzadeh G. Nahum V. Gene therapy for regenerative medicine. Pharmaceutics 2023 15 3 856 10.3390/pharmaceutics15030856 36986717
    [Google Scholar]
  107. Li J. Wang P. Zhou T. Neuroprotective effects of interleukin 10 in spinal cord injury. Front. Mol. Neurosci. 2023 16 1214294 10.3389/fnmol.2023.1214294 37492521
    [Google Scholar]
  108. Sainz-Ramos M. Gallego I. Villate-Beitia I. How far are non‐viral vectors to come of age and reach clinical translation in gene therapy? Int. J. Mol. Sci. 2021 22 14 7545 10.3390/ijms22147545 34299164
    [Google Scholar]
  109. Shchaslyvyi A.Y. Antonenko S.V. Tesliuk M.G. Telegeev G.D. Current state of human gene therapy: Approved products and vectors. Pharmaceuticals 2023 16 10 1416 10.3390/ph16101416 37895887
    [Google Scholar]
  110. Zong Y. Li H. Liao P. Mitochondrial dysfunction: Mechanisms and advances in therapy. Signal Transduct. Target. Ther. 2024 9 1 124 10.1038/s41392‑024‑01839‑8 38744846
    [Google Scholar]
  111. Yang T. Yuan, Braun M, Lembke W, McBlane F, Kamerud J, DeWall S. Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper. Mol. Ther. Methods Clin. Dev. 2022 26 471 494 10.1016/j.omtm.2022.07.018
    [Google Scholar]
  112. Tang Y. Fakhari S. Huntemann E.D. Immunosuppression reduces rAAV2.5T neutralizing antibodies that limit efficacy following repeat dosing to ferret lungs. Mol. Ther. Methods Clin. Dev. 2023 29 70 80 10.1016/j.omtm.2023.02.015 36950451
    [Google Scholar]
  113. Drago D. Foss-Campbell B. Wonnacott K. Barrett D. Ndu A. Global regulatory progress in delivering on the promise of gene therapies for unmet medical needs. Mol. Ther. Methods Clin. Dev. 2021 21 524 529 10.1016/j.omtm.2021.04.001 33997101
    [Google Scholar]
  114. Cornetta K. Lin T.Y. Pellin D. Kohn D.B. Meeting F.D.A. Meeting F.D.A. Guidance recommendations for replication-competent virus and insertional oncogenesis testing. Mol. Ther. Methods Clin. Dev. 2023 28 28 39 10.1016/j.omtm.2022.11.009 36588821
    [Google Scholar]
  115. Srivastava A. Mallela K.M.G. Deorkar N. Brophy G. Manufacturing challenges and rational formulation development for AAV viral vectors. J. Pharm. Sci. 2021 110 7 2609 2624 10.1016/j.xphs.2021.03.024 33812887
    [Google Scholar]
  116. Erpelding J.M. Lauder A.J. Neuropathy. Musculoskeletal Examination of the Elbow, Wrist, and Hand: Making the Complex Simple. CRC Press 2022 183 211 10.1201/9781003525103‑12
    [Google Scholar]
  117. Kaur C. Villarreal E. Cabe M.H. Langert K.A. Blood nerve barrier permeability enables nerve targeting of circulating nanoparticles in experimental autoimmune neuritis. Sci. Rep. 2025 15 1 11763 10.1038/s41598‑025‑96231‑z 40189681
    [Google Scholar]
  118. Butt M. Zaman M. Ahmad A. Appraisal for the potential of viral and nonviral vectors in gene therapy: A review. Genes 2022 13 8 1370 10.3390/genes13081370 36011281
    [Google Scholar]
  119. Epstein A.L. Rabkin S.D. Safety of non-replicative and oncolytic replication-selective HSV vectors. Trends Mol. Med. 2024 30 8 781 794 10.1016/j.molmed.2024.05.014 38886138
    [Google Scholar]
  120. Barnes L.F. Draper B.E. Chen Y.T. Powers T.W. Jarrold M.F. Quantitative analysis of genome packaging in recombinant AAV vectors by charge detection mass spectrometry. Mol. Ther. Methods Clin. Dev. 2021 23 87 97 10.1016/j.omtm.2021.08.002 34631929
    [Google Scholar]
  121. Ricobaraza A. Gonzalez-Aparicio M. Mora-Jimenez L. Lumbreras S. Hernandez-Alcoceba R. High-capacity adenoviral vectors: Expanding the scope of gene therapy. Int. J. Mol. Sci. 2020 21 10 3643 10.3390/ijms21103643 32455640
    [Google Scholar]
  122. Guedon JMG Wu S Zheng X Current gene therapy using viral vectors for chronic pain. Mol Pain 2015 11 s12990-015-0018-1 10.1186/s12990‑015‑0018‑1 25962909
    [Google Scholar]
  123. Tenchov R. Hughes K.J. Ganesan M. Transforming medicine: Cutting-edge applications of nanoscale materials in drug delivery. ACS Nano 2025 19 4 4011 4038 10.1021/acsnano.4c09566 39823199
    [Google Scholar]
  124. Kashyap B.K. Singh V.V. Solanki M.K. Kumar A. Ruokolainen J. Kesari K.K. Smart nanomaterials in cancer theranostics: Challenges and opportunities. ACS Omega 2023 8 16 14290 14320 10.1021/acsomega.2c07840 37125102
    [Google Scholar]
  125. Ekhator C. Qureshi M.Q. Zuberi A.W. Advances and opportunities in nanoparticle drug delivery for central nervous system disorders: A review of current advances. Cureus 2023 15 8 e44302 10.7759/cureus.44302 37649926
    [Google Scholar]
  126. Liu J. Wang T. Dong J. Lu Y. The blood–brain barriers: Novel nanocarriers for central nervous system diseases. J. Nanobiotechnology 2025 23 1 146 10.1186/s12951‑025‑03247‑8 40011926
    [Google Scholar]
  127. Klinkovskij A. Shepelev M. Isaakyan Y. Aniskin D. Ulasov I. Advances of genome editing with CRISPR/Cas9 in neurodegeneration: The right path towards therapy. Biomedicines 2023 11 12 3333 10.3390/biomedicines11123333 38137554
    [Google Scholar]
  128. Choi H. Choi W.S. Jeong J.O. A review of advanced hydrogel applications for tissue engineering and drug delivery systems as biomaterials. Gels 2024 10 11 693 10.3390/gels10110693 39590049
    [Google Scholar]
  129. Cao J. Wu B. Yuan P. Liu Y. Hu C. Advances in research of hydrogel microneedle-based delivery systems for disease treatment. Pharmaceutics 2024 16 12 1571 10.3390/pharmaceutics16121571 39771550
    [Google Scholar]
  130. Pistollato F. Furtmann F. Abitbol S. Leveraging innovative research tools to meet public health challenges: A BioMed21 workshop report. NAM Journal 2025 1 100023 10.1016/j.namjnl.2025.100023
    [Google Scholar]
/content/journals/raddf/10.2174/0126673878372806251128113526
Loading
/content/journals/raddf/10.2174/0126673878372806251128113526
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