Development of drug loaded silver nanoparticle composite chitosan film for burn wound healing

Abstract

In this study, a novel topical film for burn wound infections was developed by combining chitosan, silver nanoparticles, and the antimicrobial drug neomycin sulfate. Chitosan, a natural polymer, was chosen for its biodegradability, biocompatibility, and antibacterial properties. Silver nanoparticles exhibited bactericidal effects against various Gram-negative and Gram-positive bacteria, while neomycin sulfate is an antimicrobial drug. The silver nanoparticles were synthesized and characterized using UV spectroscopy, dynamic light scattering, and zeta potential. A film was formed on surgical dressing material containing chitosan, silver nanoparticles, and neomycin sulfate and evaluated for in-vitro anti-microbial activity and in-vivo wound healing activity on rat model. Antimicrobial activity of film showed significant differences compared to chitosan solution, silver nanoparticles, and neomycin sulfate. X-ray diffraction and FT-IR data suggested that the drug and formulation were in an amorphous form, with no interactions between the drug and excipient. The wound healing properties of neomycin sulfate-loaded silver nanoparticle-chitosan film were significantly higher than chitosan film, silver nanoparticle-containing chitosan film, and silver sulfadiazine ointment (Burn cool). Notably, the neomycin sulfate-loaded silver nanoparticle-chitosan film have significantly enhanced wound healing and can be a potential alternative in treatment of burn wound.

Keywords

• Antimicrobial activity
• chitosan
• neomycin sulphate
• silver nanoparticle
• wound healing

References

1. [1] Xu C, Tian LH. LncRNA XIST promotes proliferation and epithelial-mesenchymal transition of retinoblastoma cells through sponge action of miR-142-5p. Eur Rev Med Pharmacol Sci. 2020; 24(18): 9256–9264. https://doi.org/10.26355/eurrev_202009_23007
2. [2] Yüksel EB, Yıldırım AM, Bal A, Kuloglu T. The effect of different topical agents (silver sulfadiazine, povidone-iodine, and sodium chloride 0.9%) on burn injuries in rats. Plast Surg Int. 2014; 2014: 907082. https://doi.org/10.1155%2F2014%2F907082
3. [3] Choi JS, Kim DW, Kim DS, Kim JO, Yong CS, Cho KH, Choi HG. Novel neomycin sulfate-loaded hydrogel dressing with enhanced physical dressing properties and wound-curing effect. Drug Del. 2016; 23(8): 2806–2812. https://doi.org/10.3109/10717544.2015.1089958
4. [4] Alotaibi BS, Shoukat M, Buabeid M, Khan AK, Murtaza G. Healing potential of neomycin-loaded electrospun nanofibers against burn wounds. J Drug Del Sci Tech. 2022; 74: 103502. https://doi.org/10.1016/j.jddst.2022.103502
5. [5] Rai M, Yadav A, Gade A. Silver Nanoparticles as a new generation of antimicrobials. Biotech Adv. 2008; 27(1): 76–83. https://doi.org/10.1016/j.biotechadv.2008.09.002
6. [6] Chen X, Schluesener HJ. Nanosilver: A nanoproduct in medical application. Tox Lett. 2008; 176(1): 1–12. https://doi.org/10.1016/j.toxlet.2007.10.004
7. [7] Yoon KY, Byeon J, Park JH, Ji JH, Bae G, Hwang J. Antimicrobial characteristics of silver aerosol nanoparticles against Bacillus subtilis bioaerosols. Env Engg Sci. 2008; 25: 289–293. https://doi.org/10.1089/ees.2007.0003
8. [8] Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Ramírez JT, Yacaman MJ. The bactericidal effect of silver nanoparticles. Nanotech. 2005; 16(10): 2346–2353. https://doi.org/10.1088/0957-4484/16/10/059

9. [9] Li Y, Leung P, Yao L, Song QW, Newton E. Antimicrobial effect of surgical masks coated with nanoparticles. J Hosp Inf. 2006; 62(1): 58–63. https://doi.org/10.1016/j.jhin.2005.04.015
10. [10] Bruna T, Maldonado-Bravo F, Jara P, Caro N. Silver nanoparticles and their antibacterial applications. Int J Mol Sci. 2021; 22(13): 7202. https://doi.org/10.3390%2Fijms22137202
11. [11] Panacek A, Kvítek L, Prucek R, Kolar M, Vecerova R, Pizúrova N, Sharma VK, Nevecna T, Zboril R. Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. J Phys Chem B. 2006; 110(33): 16248-16253. https://doi.org/10.1021/jp063826h
12. [12] Birla SS, Tiwari VV, Gade AK, Ingle AP, Yadav AP, Rai MK. Fabrication of silver nanoparticles by Phoma glomerata and its combined effect against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Lett Appl Microbiol. 2009; 48(2): 173-179. https://doi.org/10.1111/j.1472-765x.2008.02510.x
13. [13] Inoue Y, Uota M, Torikai T, Watari T, Noda I, Hotokebuchi T, Yada M. Antibacterial properties of nanostructured silver titanate thin films formed on a titanium plate. J Biomed Mater Res A. 2010; 92(3): 1171-1180. https://doi.org/10.1002/jbm.a.32456
14. [14] Singh R, Shitiz K, Singh A. Chitin and chitosan: Biopolymers for wound management. Int Wound J. 2017; 14(6): 1276-1289. https://doi.org/10.1111/iwj.12797
15. [15] Ueno H, Mori T, Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv Drug Deliv Rev. 2001; 52(2): 105-115. https://doi.org/10.1016/s0169-409x(01)00189-2
16. [16] Rabea EI, Badawy ME, Stevens CV, Smagghe G, Steurbaut W. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules. 2003; 4(6): 1457-1465. https://doi.org/10.1021/bm034130m
17. [17] Li P, Poon YF, Li W, Zhu HY, Yeap SH, Cao Y, Qi X, Zhou C, Lamrani M, Beuerman RW, Kang ET, Mu Y, Li CM, Chang MW, Leong SS, Chan-Park MB. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nat Mater. 2011; 10(2): 149-156. https://doi.org/10.1038/nmat2915
18. [18] Shi C, Zhu Y, Ran X, Wang M, Su Y, Cheng T. Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res. 2006; 133(2): 185-192. https://doi.org/10.1016/j.jss.2005.12.013
19. [19] Zhao D, Yu S, Sun B, Gao S, Guo S, Zhao K. Biomedical applications of chitosan and its derivative nanoparticles. Polymers (Basel). 2018; 10(4): 462. https://doi.org/10.3390%2Fpolym10040462
20. [20] Loo HL, Goh BH, Lee LH, Chuah LH. Application of chitosan-based nanoparticles in skin wound healing. Asian J Pharm Sci. 2022; 17(3): 299-332. https://doi.org/10.1016%2Fj.ajps.2022.04.001
21. [21] Kim IY, Seo SJ, Moon HS, Yoo MK, Park IY, Kim BC, Cho CS. Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv. 2008; 26(1) :1-21. https://doi.org/10.1016/j.biotechadv.2007.07.009
22. [22] Xia Y, Wang D, Liu D, Su J, Jin Y, Wang D, Han B, Jiang Z, Liu B. Applications of chitosan and its derivatives in skin and soft tissue diseases. Front Bioeng Biotechnol. 2022; 10: 894667. https://doi.org/10.3389%2Ffbioe.2022.894667
23. [23] Senel S, McClure SJ. Potential applications of chitosan in veterinary medicine. Adv Drug Deliv Rev. 2004; 56(10): 1467-1480. https://doi.org/10.1016/j.addr.2004.02.007
24. [24] Koide SS. Chitin-chitosan: Properties, benefits and risks. Nutrition Res. 1998; 18(6): 1091–1101. https://doi.org/10.1016/S0271-5317(98)00091-8
25. [25] Kong M, Chen XG, Xing K, Park HJ. Antimicrobial properties of chitosan and mode of action: A state of the art review. Int J Food Microbiol. 2010; 144(1): 51-63. https://doi.org/10.1016/j.ijfoodmicro.2010.09.012
26. [26] Andres Y, Giraud L, Gerente C, Le Cloirec P. Antibacterial effects of chitosan powder: Mechanisms of action. Environ Technol. 2007; 28(12): 1357-1363. https://doi.org/10.1080/09593332808618893
27. [27] Raafat D, von Bargen K, Haas A, Sahl HG. Insights into the mode of action of chitosan as an antibacterial compound. Appl Environ Microbiol. 2008 ;74(12):3764-3773. https://doi.org/10.1128%2FAEM.00453-08
28. [28] Rezvani Ghomi E, Khalili S, Nouri Khorasani S, Esmaeely Neisiany R, Ramakrishna S. Wound dressings: Current advances and future directions. J Appl Polym Sci. 2019; 136(27): 47738. https://doi.org/10.1002/app.47738
29. [29] López-Miranda A,; López-Valdivieso A, Viramontes-Gamboa G. Silver nanoparticles synthesis in aqueous solutions using sulfite as reducing agent and sodium dodecyl sulfate as stabilizer. J Nanoparticle Res. 2012; 14(9): 1101. https://doi.org/10.1007/s11051-012-1101-4.
30. [30] Shah VV, Bharatiya B, Mishra M, Ray D, Shah DO. Molecular Insights into sodium dodecyl sulphate mediated control of size for silver nanoparticles. J Mol Liq. 2019; 273, 222–230. https://doi.org/10.1016/j.molliq.2018.10.042.
31. [31] Patel K, Bharatiya B, Mukherjee T, Soni T, Shukla A, Suhagia BN. Role of stabilizing agents in the formation of stable silver nanoparticles in aqueous solution: Characterization and stability study. J Dispers Sci Technol. 2017; 38(5): 626–631. https://doi.org/10.1080/01932691.2016.1185374
32. [32] Radoń A, Łukowiec D. Silver nanoparticles synthesized by UV-irradiation method using chloramine T as modifier: Structure, formation mechanism and catalytic activity. Cryst Eng Comm. 2018; 20(44): 7130–7136. https://doi.org/10.1039/C8CE01379A
33. [33] Rheima AM, Mohammed MA, Jaber SH, Hameed SA. Synthesis of silver nanoparticles using the UV-Irradiation technique in an antibacterial application. J Southwest Jiaotong Uni. 2019; 54(5): 34. https://doi.org/10.35741/issn.0258-2724.54.5.34
34. [34] Iravani S, Korbekandi H, Mirmohammadi SV, Zolfaghari B. Synthesis of silver nanoparticles: Chemical, physical and biological methods. Res Pharm Sci. 2014; 9(6): 385-406.
35. [35] Ijaz Hussain J, Kumar S, Adil Hashmi A, Khan Z. Silver nanoparticles: Preparation, characterization, and kinetics. Adv Mater Lett. 2011; 2(3): 188–194. https://doi.org/10.5185/amlett.2011.1206
36. [36] Pansara C, Mishra R, Mehta T, Parikh A, Garg S. Formulation of chitosan stabilized silver nanoparticle-containing wound healing film: In vitro and in vivo characterization. J Pharm Sci. 2020; 109(7): 2196-2205. https://doi.org/10.1016/j.xphs.2020.03.028
37. [37] Geoprincy G, Saravanan P, Gandhi NN, Renganathan S. A novel approach for studying the combined antimicrobial effects of silver nanoparticles and antibiotics through agar over layer method and disk diffusion method. Digest J Nanomater Biostruct.. 2011; 6(4): 1557–1565.
38. [38] Huang L, Dai T, Xuan Y, Tegos GP, Hamblin MR. Synergistic combination of chitosan acetate with nanoparticle silver as a topical antimicrobial: Efficacy against bacterial burn infections. Antimicrob Agents Chemother. 2011; 55(7): 3432-3438. https://doi.org/10.1128%2FAAC.01803-10