Wound healing effects of dexpanthenol-loaded core/shell electrospun nanofibers: Implication of oxidative stress in wound healing

Document Type : Original Article

Authors

1 Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran

2 Department of Oral & Maxillofacial Surgery, School of Dentistry, Bushehr University of Medical Sciences, Bushehr, Iran

3 Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran

4 Nuclear Medicine and Molecular Imaging Research Center, Bushehr University of Medical Sciences, Bushehr, Iran

5 Department of Pharmacology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

Abstract

Objective(s): Knowing the detrimental role of oxidative stress in wound healing and the anti-oxidant properties of Dexpanthenol (Dex), we aimed to produce Dex-loaded electrospun core/shell nanofibers for wound healing study. The novelty was measuring oxidative stress in wounds to know how oxidative stress was affected by Dex-loaded fibers.
Materials and Methods: TPVA solution containing Dex 6% (w/v) (core) and PVA/chitosan solution (shell) were coaxially electrospun with variable injection rates of the shell solution. Fibers were then tested for physicochemical properties, drug release profile, and effects on wound healing. Levels of tissue lipid peroxidation and superoxide dismutase activity were measured.
Results: Fibers produced at shell injection rate of 0.3 ml/hr (F3 fibers) showed core/shell structure with an average diameter of 252 nm, high hydrophilicity (swelling: 157% at equilibrium), and low weight loss (13.6%). Dex release from F3 fibers seemed to be ruled by the Fickian mechanism based on the Korsmeyer-Peppas model (R2 = 0.94, n = 0.37). Dex-loaded F3 fibers promoted fibroblast viability (128.4%) significantly on day 5 and also accelerated wound healing compared to the neat F3 fibers at macroscopic and microscopic levels on day 14 post-wounding. The important finding was a significant decrease in malondialdehyde (0.39 nmol/ mg protein) level and an increase in superoxide dismutase (5.29 unit/mg protein) activity in Dex-loaded F3 fiber-treated wound tissues. 
Conclusion: Dex-loaded core/shell fibers provided nano-scale scaffolds with sustained release profile that significantly lowered tissue oxidative stress. This finding pointed to the importance of lowering oxidative stress to achieve proper wound healing. 

Keywords

Main Subjects


1. Hu SC-S, Lan C-CE. High-glucose environment disturbs the physiologic functions of keratinocytes: focusing on diabetic wound healing. J Dermatol Sci 2016; 84:121-127.
2. Cha JW, Piao MJ, Kim KC, Yao CW, Zheng J, Kim SM, et al. The polyphenol chlorogenic acid attenuates UVB-mediated oxidative stress in human HaCaT keratinocytes. Biomol Ther (Seoul) 2014; 22:136-142.
3. Gorski J, Proksch E, Baron JM, Schmid D, Zhang L. Dexpanthenol in wound healing after medical and cosmetic interventions (postprocedure wound healing). Pharmaceuticals 2020; 13:138-149.
4. Tutun B, Elbe H, Vardi N, Parlakpinar H, Polat A, Gunaltili M, et al. Dexpanthenol reduces diabetic nephropathy and renal oxidative stress in rats. Biotech Histochem 2019; 94:84-91.
5. Gülmez A, Bektaşoğlu PK, Tönge Ç, Yaprak A, Türkoğlu ME, Önder E, et al. Neuroprotective effects of dexpanthenol on rabbit spinal cord ischemia/reperfusion injury model. World Neurosurg 2022; 167:e172-e183.
6. Ucar M, Aydogan MS, Vardı N, Parlakpınar H, editors. Protective effect of dexpanthenol on ischemia-reperfusion-induced liver injury. Transplant Proc 2018; 50:3135-3143.
7. Tottoli EM, Dorati R, Genta I, Chiesa E, Pisani S, Conti B. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics 2020; 12:735-764.
8. Keshvardoostchokami M, Majidi SS, Huo P, Ramachandran R, Chen M, Liu B. Electrospun nanofibers of natural and synthetic polymers as artificial extracellular matrix for tissue engineering. Nanomaterials 2021; 11:21-43.
9. Liu X, Xu H, Zhang M, Yu DG. Electrospun medicated nanofibers for wound healing: Review. Membranes (Basel) 2021; 11:770-791.
10. Wang J, Planz V, Vukosavljevic B, Windbergs M. Multifunctional electrospun nanofibers for wound application–Novel insights into the control of drug release and antimicrobial activity. Eur J Pharm Biopharm 2018; 129:175-183.
11. Keshvardoostchokami M, Majidi SS, Huo P, Ramachandran R, Chen M, Liu B. Electrospun nanofibers of natural and synthetic polymers as artificial extracellular matrix for tissue engineering. Nanomaterials 2020; 11:21-43.
12. Stachewicz U, Qiao T, Rawlinson SC, Almeida FV, Li W-Q, Cattell M, et al. 3D imaging of cell interactions with electrospun PLGA nanofiber membranes for bone regeneration. Acta biomaterialia 2015; 27:88-100.
13. Yousefi P, Dini G, Movahedi B, Vaezifar S, Mehdikhani M. Polycaprolactone/chitosan core/shell nanofibrous mat fabricated by electrospinning process as carrier for rosuvastatin drug. Polymer Bulletin 2022; 79:1627-1645.
14. Bano I, Arshad M, Yasin T, Ghauri MA, Younus M. Chitosan: A potential biopolymer for wound management. Int J Biol Macromol 2017; 102:380-383.
15. Behera SS, Das U, Kumar A, Bissoyi A, Singh AK. Chitosan/TiO2 composite membrane improves proliferation and survival of L929 fibroblast cells: Application in wound dressing and skin regeneration. Int J Biol Macromol 2017; 98:329-340.
16. Singhvi G, Singh M. In-vitro drug release characterization models. Int J Pharm Stud Res 2011; 2:77-84.
17. Mæhre HK, Dalheim L, Edvinsen GK, Elvevoll EO, Jensen I-J. Protein determination—method matters. Foods 2018; 7:5-15.
18. Premkumar PS. Preparation and electrical studies on pure and oxygen plasma treated polyvinyl alcohol films. J Mater Res Technol 2019; 8:2232-2237.
19. Tamizi E, Azizi M, Dorraji MSS, Dusti Z, Panahi-Azar V. Stabilized core/shell PVA/SA nanofibers as an efficient drug delivery system for dexpanthenol. Polymer Bulletin 2018; 75:1-14.
20. Sevinç-Özakar R, Seyret E, Özakar E, Adıgüzel MC. Nanoemulsion-based hydrogels and organogels containing propolis and dexpanthenol: Preparation, characterization, and comparative evaluation of stability, antimicrobial, and cytotoxic properties. Gels 2022; 8:578-601.
21. Queiroz MF, Teodosio Melo KR, Sabry DA, Sassaki GL, Rocha HAO. Does the use of chitosan contribute to oxalate kidney stone formation? Mar Drugs 2014; 13:141-158.
22. Zhou X, Ruan Q, Ye Z, Chu Z, Xi M, Li M, et al. Resveratrol accelerates wound healing by attenuating oxidative stress-induced impairment of cell proliferation and migration. Burns 2021; 47:133-139.
23. de Christo Scherer MM, Marques FM, Figueira MM, Peisino MCO, Schmitt EFP, Kondratyuk TP, et al. Wound healing activity of terpinolene and α-phellandrene by attenuating inflammation and oxidative stress in vitro. J Tissue Viability 2019; 28:94-99.
24. Tanrıverdi ST, Suat B, Azizoğlu E, Köse FA. In-vitro evaluation of dexpanthenol-loaded nanofiber mats for wound healing. Trop J Pharm Res 2018; 17:387-394.
25. Mousivand Z, Ayazi H, Abdollahi A, Akbari H, Raoufi M, Sharifikolouei E. Hybrid electrospun scaffold loaded with argireline acetate and dexpanthenol for skin regeneration. Int J Polym Mater Polym Biomater 2022; 72:1179-1190.
26. Najafiasl M, Osfouri S, Azin R, Zaeri S. Alginate-based electrospun core/shell nanofibers containing dexpanthenol: A good candidate for wound dressing. J Drug Delivery Sci Technol 2020; 57:101708-101715.
27. Najafiasl M, Osfouri S, Azin R, Zaeri S. Fabrication, characterization and in vivo evaluation of dexpanthenol sustained-release nanofibers for wound healing. Polymer Testing 2020; 91:106827-106834.
28. Farboudi A, Nouri A, Shirinzad S, Sojoudi P, Davaran S, Akrami M, et al. Synthesis of magnetic gold coated poly (ε-caprolactonediol) based polyurethane/poly (N-isopropylacrylamide)-grafted-chitosan core-shell nanofibers for controlled release of paclitaxel and 5-FU. Int J Biol Macromol 2020; 150:1130-1140.
29. Yan E, Jiang J, Yang X, Fan L, Wang Y, An Q, et al. pH-sensitive core-shell electrospun nanofibers based on polyvinyl alcohol/polycaprolactone as a potential drug delivery system for the chemotherapy against cervical cancer. J Drug Delivery Sci Technol 2020; 55:101455.
30. Santadkha T, Skolpap W, Thitapakorn V. Diffusion Modeling and in vitro release kinetics studies of curcumin− loaded superparamagnetic nanomicelles in cancer drug delivery system. J Pharm Sci 2022; 111:1690-1699.
31. Lee JH, Yeo Y. Controlled drug release from pharmaceutical nanocarriers. Chem Eng Sci 2015; 125:75-84.
32. Oun R, Plumb JA, Wheate NJ. A cisplatin slow-release hydrogel drug delivery system based on a formulation of the macrocycle cucurbit [7] uril, gelatin and polyvinyl alcohol. J Inorg Biochem 2014; 134:100-105.
33. Miron-Mendoza M, Lin X, Ma L, Ririe P, Petroll WM. Individual versus collective fibroblast spreading and migration: regulation by matrix composition in 3D culture. Exp Eye Res 2012; 99:36-44.
34. Deng L, Du C, Song P, Chen T, Rui S, Armstrong DG, et al. The role of oxidative stress and anti-oxidants in diabetic wound healing. Oxid Med Cell Longev 2021; 2021:1-11.
35. Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 2020; 59:101036-101047.