Synthesis of Chitosan-Based Hydrogels as a Novel Drug Release Device for Wound Healing

Abstract

The development of the porous, biocompatible and biodegradable hydrogels has been gaining much attention for wound dressing applications. The hydrogels prepared using freeze-thawing method present important properties of high biocompatibility and nontoxicity. The hydrogels that are able to release drugs for prolonged time are widely used biomaterials for wound healing. In this study chitosan CS -based poly-ε-caprolactone PCL hydrogels were prepared using poly vinyl alcohol PVA , poly ethylene glycol PEG and poly vinyl pyrrolidone PVP . PVA-CS-PCL hydrogels only could remain stable at room temperature after synthesis. The properties of the hydrogels were determined with SEM, FTIR, swelling tests and degradation tests. The drugs of ceftazidime CZ as an antibiotic and ketoprofen KP as an analgesic were loaded onto the hydrogels and the loaded hydrogels were used for the drug release studies at pH 5.5 and pH 7.4. All these results suggest that the developed PVA-CS-PCL hydrogels offer significant potential as a wound dressing material.

Keywords

• Chitosan-based hydrogel, Wound dressing, Drug release, Ceftazidime, Ketoprofen.

References

1. Gupta, B, Agarwal, R, Sarwar Alam, M. Antimicrobial and release study of drug loaded PVA/PEO/CMC wound dressings. Journal of Materials Science: Materials in Medicine 25 (2014) 1613-1622.
2. Maver, T, Maver, U, Mostegel, F, Griesser, T, Spirk, S, Smrke, DM, Stana-Kleinschek, K. Cellulose based thin films as a platform for drug release studies to mimick wound dressing materials. Cellulose 22 (2015) 749-761.
3. Zahedi, P, Rezaeian, I, Ranaei-Siadat, S-O, Jafari, S-H, Supaphol, P. A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages. Polymers for Advanced Technologies 21 (2010) 77-95.
4. Kevadiya, BD, Rajkumar, S, Bajaj, HC, Chettiar, SS, Gosai, K, Brahmbhatt, H, Bhatt, AS, Barvaliya, YK, Dave, GS, Kothari, RK. Biodegradable gelatin–ciprofloxacin–montmorillonite composite hydrogels for controlled drug release and wound dressing application. Colloids and Surfaces B: Biointerfaces 122 (2014) 175-183.
5. Thakur, RA, Florek, CA, Kohn, J, Michniak, BB. Electrospun nanofibrous polymeric scaffold with targeted drug release profiles for potential application as wound dressing. International Journal of Pharmaceutics 364 (2008) 87-93.
6. Zilberman, M, Egozi, D, Shemesh, M, Keren, A, Mazor, E, Baranes-Zeevi, M, Goldstein, N, Berdicevsky, I, Gilhar, A, Ullmann, Y. Hybrid wound dressings with controlled release of antibiotics: Structure-release profile effects and in vivo study in a guinea pig burn model. Acta Biomaterialia 22 (2015) 155-163.
7. Boateng, JS, Pawar, HV, Tetteh, J. Polyox and carrageenan based composite film dressing containing anti-microbial and anti-inflammatory drugs for effective wound healing. International Journal of Pharmaceutics 441 (2013) 181-191.
8. Safdari, M, Shakiba, E, Kiaie, SH, Fattahi, A. Preparation and characterization of ceftazidime loaded electrospun silk fibroin/gelatin mat for wound dressing. Fibers and Polymers 17 (2016) 744-750.

9. Yu, H, Xiao, C. Synthesis and properties of novel hydrogels from oxidized konjac glucomannan crosslinked gelatin for in vitro drug delivery. Carbohydrate Polymers 72 (2008) 479- 489.
10. Guan, Y, Bian, J, Peng, F, Zhang, X-M, Sun, R-C. High strength of hemicelluloses based hydrogels by freeze/thaw technique. Carbohydrate Polymers 101 (2014) 272-280.
11. Behnoodfar, D, Dadbin, S, Frounchi, M. PLA microspheres- embedded PVA hydrogels prepared by gamma-irradiation and freeze-thaw methods as drug release carriers. International Journal of Polymeric Materials and Polymeric Biomaterials 62 (2013) 28-33.
12. Gonzalez, JS, Ludueña, LN, Ponce, A, Alvarez, VA. Poly(vinyl alcohol)/cellulose nanowhiskers nanocomposite hydrogels for potential wound dressings. Materials Science and Engineering: C 34 (2014) 54-61.
13. Kamoun, EA, Kenawy, E-RS, Tamer, TM, El-Meligy, MA, Mohy Eldin, MS. Poly (vinyl alcohol)-alginate physically crosslinked hydrogel membranes for wound dressing applications: Characterization and bio-evaluation. Arabian Journal of Chemistry 8 (2015) 38-47.
14. Tamahkar, E, Özkahraman, B. Potential evaluation of PVA- based hydrogels for biomedical applications. Hittite Journal of Science and Engineering 2 (2015) 165-171.
15. Hassan, CM, Peppas, NA, Secondary Structure and applications of poly(vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. In Biopolymers · PVA hydrogels, anionic polymerisation nanocomposites, Springer Berlin Heidelberg, Berlin, Heidelberg, 2000.
16. Dai, T, Tanaka, M, Huang, Y-Y, Hamblin, MR. Chitosan preparations for wounds and burns: Antimicrobial and wound-healing effects. Expert review of anti-infective therapy 9 (2011) 857-879.
17. Thomas, R, Soumya, KR, Mathew, J, Radhakrishnan, EK. Electrospun polycaprolactone membrane incorporated with biosynthesized silver nanoparticles as effective wound dressing material. Applied Biochemistry and Biotechnology 176 (2015) 2213-2224.
18. Kamoun, EA, Kenawy, E-RS, Chen, X. A review on polymeric hydrogel membranes for wound dressing applications: PVA- based hydrogel dressings. Journal of Advanced Research 8 (2017) 217-233.
19. Ahmed, AS, Mandal, UK, Taher, M, Susanti, D, Jaffri, JM. PVA-PEG physically cross-linked hydrogel film as a wound dressing: Experimental design and optimization. Pharmaceutical Development and Technology (2017) 1-25.
20. Dai, X-Y, Nie, W, Wang, Y-C, Shen, Y, Li, Y, Gan, S-J. Electrospun emodin polyvinylpyrrolidone blended nanofibrous membrane: A novel medicated biomaterial for drug delivery and accelerated wound healing. Journal of Materials Science: Materials in Medicine 23 (2012) 2709- 2716.
21. Doulabi, HA, Mequanint, K, Mohammadi, H. Blends and nanocomposite biomaterials for articular cartilage tissue engineering. Materials 7 (2014)
22. Islam, A, Yasin, T, Gull, N, Khan, SM, Munawar, MA, Shafiq, M, Sabir, A, Jamil, T. Evaluation of selected properties of biocompatible chitosan/poly(vinyl alcohol) blends. International Journal of Biological Macromolecules 82 (2016) 551-556.
23. Afshari, MJ, Sheikh, N, Afarideh, H. PVA/CM-chitosan/ honey hydrogels prepared by using the combined technique of irradiation followed by freeze-thawing. Radiation Physics and Chemistry 113 (2015) 28-35.
24. Jannesari, M, Varshosaz, J, Morshed, M, Zamani, M. Composite poly (vinyl alcohol)/poly (vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs. Int J Nanomedicine 6 (2011) 993-1003.
25. Hsu, Y-H, Lin, C-T, Yu, Y-H, Chou, Y-C, Liu, S-J, Chan, E-C. Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers. International Journal of Nanomedicine 11 (2016) 3927—3937.
26. Kataria, K, Gupta, A, Rath, G, Mathur, RB, Dhakate, SR. In vivo wound healing performance of drug loaded electrospun composite nanofibers transdermal patch. International
27. Journal of Pharmaceutics 469 (2014) 102-110.
28. Atzet, S, Curtin, S, Trinh, P, Bryant, S, Ratner, B. [33] Josef, E, Zilberman, M, Bianco-Peled, H. Composite alginate Degradable poly(2-hydroxyethyl methacrylate)-co- polycaprolactone hydrogels for tissue engineering scaffolds. Biomacromolecules 9 (2008) 3370-3377.
29. Jeong, B, Bae, YH, Kim, SW. Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers. Journal of Controlled Release 63 (2000) 155-163.
30. Freiberg, S, Zhu, XX. Polymer microspheres for controlled drug release. International Journal of Pharmaceutics 282 (2004) 1-18.
31. Kamaly, N, Yameen, B, Wu, J, Farokhzad, OC. Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release. Chemical Reviews 116 (2016) 2602-2663.
32. Shafaghi, S, Moghadam, PN, Fareghi, AR, Baradarani, MM. Synthesis and characterization of a drug-delivery system based on melamine-modified poly(vinyl acetate-co-maleic anhydride) hydrogel. Journal of Applied Polymer Science 131 (2014).
33. Shefy-Peleg, A, Foox, M, Cohen, B, Zilberman, M. Novel antibiotic-eluting gelatin-alginate soft tissue adhesives for various wound closing applications. International Journal of Polymeric Materials and Polymeric Biomaterials 63 (2014) 699-707. hydrogels: An innovative approach for the controlled release of hydrophobic drugs. Acta Biomaterialia 6 (2010) 4642- 4649.
34. Huang, Y, Yu, H, Xiao, C. Ph-sensitive cationic guar gum/ poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release. Carbohydrate Polymers 69 (2007) 774- 783.
35. Hiep, NT, Khon, HC, Niem, VVT, Toi, VV, Ngoc Quyen, T, Hai, ND, Ngoc Tuan Anh, M. Microwave-assisted synthesis of chitosan/polyvinyl alcohol silver nanoparticles gel for wound dressing applications. International Journal of Polymer Science 2016 (2016) 11.
36. Elsner, JJ, Berdicevsky, I, Zilberman, M. In vitro microbial inhibition and cellular response to novel biodegradable composite wound dressings with controlled release of antibiotics. Acta Biomaterialia 7 (2011) 325-336.