In situ Crosslinking System of Gelatin with Acrylated β-cyclodextrin Towards the Fabrication of Hydrogels for Sustained Drug Release

Year 2020, Volume: 7 Issue: 2, 597 - 608, 23.06.2020

Mehmet Arslan

https://doi.org/10.18596/jotcsa.717856

Cited By: 2

Abstract

Cyclodextrins (CDs) are of interest in fabrication of various polymeric platforms; especially the crosslinked networks that possess unique advantages in biomedical applications. Benefiting from the abilities of CDs to form inclusion complexes with hydrophobic drug molecules, hydrogel-based sustained drug platforms employ CDs as nano-buckets in the network structure. In the current study, we report on the fabrication of gelatin based hydrogels chemically crosslinked with acrylated β-cyclodextrin (β-CD) as sustained drug release platforms. A simple and practical synthesis of crosslinked networks was achieved by Michael addition reaction of gelatin amino functionalities onto acryloyl groups of modified β-CD. Tunable synthesis of hydrogels incorporating different amount of β-CD molecules were maintained by simple adjustment of the reaction stoichiometry between amine and acrylate groups. The resulting hydrogels were characterized by their equilibrium swelling ratios and rheological properties. Thus obtained hydrogels were evaluated in terms of their drug loading capacities and sustained release efficiencies. The results demonstrated that the amount of drug loading and prolonged release is dependent on the amount of β-CD in the gel network. Owing to their in situ gel forming abilities, these hydrogels can be used as injectable formulations for various biomedical applications.

Keywords

Drug releasing hydrogels, β-cyclodextrin, aza-Michael addition, injectable hydrogels

References

• 1. Peppas NA, Hilt JZ, Khademhosseini A, Langer R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Advanced Materials. 2006. doi:10.1002/adma.200501612
• 2. Caló E, Khutoryanskiy V V. Biomedical applications of hydrogels: A review of patents and commercial products. European Polymer Journal. 2015. doi:10.1016/j.eurpolymj.2014.11.024
• 3. Hoffman AS. Hydrogels for biomedical applications. Advanced Drug Delivery Reviews. 2012. doi:10.1016/j.addr.2012.09.010
• 4. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chemical Reviews. 2001. doi:10.1021/cr000108x
• 5. Wang H, Heilshorn SC. Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering. Advanced Materials. 2015. doi:10.1002/adma.201501558
• 6. Geckil H, Xu F, Zhang X, Moon S, Demirci U. Engineering hydrogels as extracellular matrix mimics. Nanomedicine. 2010. doi:10.2217/nnm.10.12
• 7. Li J, Mooney DJ. Designing hydrogels for controlled drug delivery. Nature Reviews Materials. 2016. doi:10.1038/natrevmats.2016.71
• 8. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Advanced Drug Delivery Reviews. 2012. doi:10.1016/j.addr.2012.09.024
• 9. Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008. doi:10.1016/j.polymer.2008.01.027
• 10. Yang JA, Yeom J, Hwang BW, Hoffman AS, Hahn SK. In situ-forming injectable hydrogels for regenerative medicine. Progress in Polymer Science. 2014. doi:10.1016/j.progpolymsci.2014.07.006
• 11. Yu L, Ding J. Injectable hydrogels as unique biomedical materials. Chemical Society Reviews. 2008. doi:10.1039/b713009k
• 12. Li Y, Rodrigues J, Tomás H. Injectable and biodegradable hydrogels: Gelation, biodegradation and biomedical applications. Chemical Society Reviews. 2012. doi:10.1039/c1cs15203c
• 13. Tiller JC. Increasing the local concentration of drugs by hydrogel formation. Angewandte Chemie - International Edition. 2003. doi:10.1002/anie.200301647
• 14. Cai S, Liu Y, Xiao ZS, Prestwich GD. Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor. Biomaterials. 2005. doi:10.1016/j.biomaterials.2005.03.012
• 15. Paul A, Hasan A, Kindi H Al, Gaharwar AK, Rao VTS, Nikkhah M, et al. Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair. ACS Nano. 2014. doi:10.1021/nn5020787
• 16. Yue K, Santiago GT, Tamayol A, Annabi N, Khademhosseini A, Hospital W, et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2016. doi:10.1016/j.biomaterials.2015.08.045.Synthesis
• 17. Olsen D, Yang C, Bodo M, Chang R, Leigh S, Baez J, et al. Recombinant collagen and gelatin for drug delivery. Advanced Drug Delivery Reviews. 2003. doi:10.1016/j.addr.2003.08.008
• 18. Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015. doi:10.1016/j.biomaterials.2015.08.045
• 19. Davidenko N, Schuster CF, Bax D V., Farndale RW, Hamaia S, Best SM, et al. Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry. J Mater Sci Mater Med. 2016. doi:10.1007/s10856-016-5763-9
• 20. Gasperini L, Mano JF, Reis RL. Natural polymers for the microencapsulation of cells. Journal of the Royal Society Interface. 2014. doi:10.1098/rsif.2014.0817
• 21. Chen YC, Lin RZ, Qi H, Yang Y, Bae H, Melero-Martin JM, et al. Functional human vascular network generated in photocrosslinkable gelatin methacrylate hydrogels. Advanced Functional Materials. 2012. doi:10.1002/adfm.201101662
• 22. Pepelanova I, Kruppa K, Scheper T, Lavrentieva A. Gelatin-methacryloyl (GelMA) hydrogels with defined degree of functionalization as a versatile toolkit for 3D cell culture and extrusion bioprinting. Bioengineering. 2018. doi:10.3390/bioengineering5030055
• 23. Young S, Wong M, Tabata Y, Mikos AG. Gelatin as a delivery vehicle for the controlled release of bioactive molecules. Journal of Controlled Release. 2005. doi:10.1016/j.jconrel.2005.09.023
• 24. Draye JP, Delaey B, Van De Voorde A, Van Den Bulcke A, De Reu B, Schacht E. In vitro and in vivo biocompatibility of dextran dialdehyde cross-linked gelatin hydrogel films. Biomaterials. 1998. doi:10.1016/S0142-9612(98)00049-0
• 25. Koshy ST, Desai RM, Joly P, Li J, Bagrodia RK, Lewin SA, et al. Click-Crosslinked Injectable Gelatin Hydrogels. Advanced Healthcare Materials. 2016. doi:10.1002/adhm.201500757
• 26. Chen B, Hu X. An injectable composite gelatin hydrogel with pH response properties. Journal of Nanomaterials. 2017. doi:10.1155/2017/5139609
• 27. Arslan M, Sanyal R, Sanyal A. Cyclodextrin embedded covalently crosslinked networks: Synthesis and applications of hydrogels with nano-containers. Polymer Chemistry. 2020. doi:10.1039/c9py01679a
• 28. Arslan M, Sanyal R, Sanyal A. Cyclodextrin-containing hydrogel networks. In: Mishra M, editor. Encyclopedia of Biomedical Polymers and Polymeric Biomaterials. Taylor and Francis: New York; 2015. p.  2243-58. Available from: https://www.taylorfrancis.com/books/e/9781466501799/chapters/10.1081%2FE-EBPP-120050543
• 29. Arslan M, Aydin D, Degirmenci A, Sanyal A, Sanyal R. Embedding well-defined responsive hydrogels with nanocontainers: Tunable materials from telechelic polymers and cyclodextrins. ACS Omega. 2017. doi:10.1021/acsomega.7b00787
• 30. Arslan M, Gevrek TN, Sanyal A, Sanyal R. Cyclodextrin mediated polymer coupling via thiol-maleimide conjugation: Facile access to functionalizable hydrogels. RSC Advances. 2014. doi:10.1039/c4ra12408a
• 31. Arslan M, Gevrek TN, Sanyal R, Sanyal A. Fabrication of poly(ethylene glycol)-based cyclodextrin containing hydrogels via thiol-ene click reaction. European Polymer Journal. 2015. doi:10.1016/j.eurpolymj.2014.08.018
• 32. M. Arslan, T. Yirmibesoglu, M. Celebi, In situ Crosslinkable Thiol-ene Hydrogels Based on PEGylated Chitosan and β-Cyclodextrin, J. Turk. Chem. Soc., Sect. A: Chem., 2018, 5, 1327–1336.
• 33. Wang FP, Li, GF, Zhou QQ, Yang CX, Wang QZ. Removal of metal ions from aqueous solution with cyclodextrin-based hydrogels. 2016; 6(5): 394-02.
• 34. Hafidz RNRM, Yaakob CM, Amin I, Noorfaizan A. Chemical and functional properties of bovine and porcine skin gelatin. Int Food Res J. 2011.
• 35. Bertoldo M, Bronco S, Gragnoli T, Ciardelli F. Modification of gelatin by reaction with 1,6-diisocyanatohexane. Macromol Biosci. 2007. doi:10.1002/mabi.200600215
• 36. De Carvalho RA, Grosso CRF. Characterization of gelatin based films modified with transglutaminase, glyoxal and formaldehyde. Food Hydrocoll. 2004. doi:10.1016/j.foodhyd.2003.10.005
• 37. Honda I, Arai K, Mitomo H. Characterization of cross-links introduced in gelatin. J Appl Polym Sci. 1997. doi:10.1002/(SICI)1097-4628(19970606)64:10<1879::AID-APP2>3.0.CO;2-F
• 38. Bigi A, Cojazzi G, Panzavolta S, Roveri N, Rubini K. Stabilization of gelatin films by crosslinking with genipin. Biomaterials. 2002. doi:10.1016/S0142-9612(02)00235-1
• 39. Liu C, Zhang Z, Liu X, Ni X, Li J. Gelatin-based hydrogels with β-cyclodextrin as a dual functional component for enhanced drug loading and controlled release. RSC Advances. 2013. doi:10.1039/c3ra42532k
• 40. Surendra K, Krishnaveni NS, Sridhar R, Rao KR. β-Cyclodextrin promoted aza-Michael addition of amines to conjugated alkenes in water. Tetrahedron Letters. 2006. doi:10.1016/j.tetlet.2006.01.124
• 41. Yeom CE, Kim MJ, Kim BM. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted efficient and versatile aza-Michael addition. Tetrahedron. 2007. doi:10.1016/j.tet.2006.11.037
• 42. Siemoneit U, Schmitt C, Alvarez-Lorenzo C, Luzardo A, Otero-Espinar F, Concheiro A, et al. Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability. Int J Pharm. 2006. doi:10.1016/j.ijpharm.2005.12.046
• 43. Jin R, Moreira Teixeira LS, Dijkstra PJ, Karperien M, van Blitterswijk CA, Zhong ZY, et al. Injectable chitosan-based hydrogels for cartilage tissue engineering. Biomaterials. 2009. doi:10.1016/j.biomaterials.2009.01.020
• 44. Das S, Subuddhi U. Studies on the complexation of diclofenac sodium with β-cyclodextrin: Influence of method of preparation. J Mol Struct. 2015. doi:10.1016/j.molstruc.2015.07.001
• 45. Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. Journal of Controlled Release. 2001. doi:10.1016/S0168-3659(01)00248-6