Synthesis and Characterization of pH-Sensitive Copolymer mPEG-acetal-PIB and Fabrication of Hydrogel for Wound Dressing
Received date: 2015-05-09
Online published: 2015-07-07
Supported by
roject supported by the National Natural Science Foundation of China (No. 21374066), the Suzhou Science and Technology Program for Industrial Application Foundation (No. SYG201429), a Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, and the State Key Lab of Chemical Resource Engineering (Beijing University of Chemical Technology) (No. CRE-2014-C-202).
An acetal-linked amphiphilic diblock copolymer, poly(ethylene glycol) methyl ether-acetal-polyisobutene (abbreviated as mPEG-acetal-PIB), was synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) “Click” reaction. The chemical composition and structures of the copolymers were characterized by 1H NMR and FT-IR analysis. The molecular weights and molecular weight distributions of the polymers were measured by gel permeation chromatography (GPC). The critical aggregation concentration (CAC), particle size parameters and morphologies of micelles self-assembled from mPEG-acetal-PIB in aqueous solution were determined by fluorescence probe method, dynamic light scattering (DLS), and transmission electron microscopy (TEM), respectively. The results showed that this amphiphilic diblock copolymer mPEG-acetal-PIB could self-assemble into spherical micelles in aqueous solution, and the average particle size of micelles was about 100 nm. Since the acetal group is unstable in weak acidic medium, it is anticipated that the diblock copolymer micelles can be dissociated in acidic environment. To verify this, DLS analysis was used to monitor the size change of micelles with the increase of degradation time under the acidic conditions. The degradation of acetal group in acidic environment resulted in the aggregation of PIB, which caused the increase of particle size. Subsequently, a-cyclodextrin (a-CD) was added into the micellar system to interact with PEG chain via inclusion complexation, resulting in the formation of physical-crosslinked supramolecular hydrogels. X-ray diffraction (XRD) was carried out to analyze the inclusion complexation and rheological test was used to monitor the gelation kinetics of hydrogels. The materials chosen to fabricate wound dressing should have good biocompatibility, thus in vitro cytotoxicity tests against L929 cells by MTT assays was carried out to study the biocompatibility of the copolymer and hydrogel. The results showed that the viability of L929 cells incubated with both the copolymer and hydrogel were higher than 80%, indicating that the copolymer and hydrogel displayed low cytotoxicity. This biocompatible hydrogel provides a moist and cool environment on the wounds and can be degraded in the acidic conditions, reducing the risk of inflammation. Therefore, it will possess great potential in the application of wound dressing.
Key words： “Click” reaction; pH-response; hydrogel; wound dressing
Ren Kai , He Jinlin , Zhang Mingzu , Wu Yixian , Ni Peihong . Synthesis and Characterization of pH-Sensitive Copolymer mPEG-acetal-PIB and Fabrication of Hydrogel for Wound Dressing[J]. Acta Chimica Sinica, 2015 , 73(10) : 1038 -1046 . DOI: 10.6023/A15050317
[1] Boateng, J. S.; Matthews, K. H.; Stevens, H. N. E.; Eccleston, G. M. J. Pharm. Sci. 2008, 97, 2892.
[2] Jayakumar, R.; Prabaharan, M.; Kumar, P. T. S.; Nair, S. V.; Tamura, H. Biotechnol. Adv. 2011, 29, 322.
[3] Zhao, L.; Song, J. X. J. Clin. Rehabilitative Tissue Eng. Res. 2007, 11, 1724. (赵琳, 宋建星, 中国组织工程研究与临床康复, 2007, 11, 1724.)
[4] Eaglstein, W. H. Dermatol. Surg. 2001, 27, 175.
[5] Field, C. K.; Kerstein, M. D. Am. J. Surg. 1994, 167, 2s-6s.
[6] Guvendiren, M.; Lu, H. D.; Burdick, J. A. Soft Matter 2012, 8, 260.
[7] Manakker, F.; Kroon-Batenburg, L. M. J.; Vermonden, T.; van Nostrum, C. F.; Hennink, W. E. Soft Matter 2010, 6, 187.
[8] Hiemstra, C.; Zhou, W.; Zhong, Z. Y.; Wouters, M.; Feijen, J. J. Am. Chem. Soc. 2007, 129, 9918.
[9] Yu, J. H.; Fan, H. L.; Huang, J.; Chen, J. H. Soft Matter 2011, 7, 7386.
[10] Rhodes, N. P. Biomaterials 2007, 28, 5131.
[11] Yu, L.; Chang, G. T.; Zhang, H.; Ding, J. D. Int. J. Pharm. 2008, 348, 95.
[12] Lemmers, M.; Sprakel, J.; Voets, I. K.; van der Gucht, J.; Stuart, M. A. C. Angew. Chem., Int. Ed. 2010, 49, 708.
[13] Wang, Q. G.; Mynar, J. L.; Yoshida, M.; Lee, E.; Lee, M.; Okuro, K.; Kinbara, K.; Aida, T. Nature 2010, 463, 339.
[14] Hunt, J. N.; Feldman, K. E.; Lynd, N. A.; Deek, J.; Campos, L. M.; Spruell, J. M.; Hernandez, B. M.; Kramer, E. J.; Hawker, C. J. Adv. Mater. 2011, 23, 2327.
[15] Zhang, Y. L.; Yang, B.; Xu, L. X.; Zhang, X. Y.; Tao, L.; Wei, Y. Acta Chim. Sinica 2013, 71, 485. (张亚玲, 杨斌, 许亮鑫, 张小勇, 陶磊, 危岩, 化学学报, 2013, 71, 485.)
[16] Silva, O. F.; Fernández, M. A.; Pennie, S. L.; Gil, R. R.; Rossi, R. H. Langmuir 2008, 24, 3718.
[17] Giacomelli, C.; Schmidt, V.; Putaux, J. L.; Narumi, A.; Kakuchi, T.; Borsali, R. Biomacromolecules 2009, 10, 449.
[18] Li, S. J.; Zhang, X. J.; Liang, H. Y.; Wang, X. R. Acta. Chim. Sinica 2012, 70, 1013. (李姝静, 张小军, 梁海燕, 王心蕊, 化学学报, 2012, 70, 1013.)
[19] Sun, L. L.; Xu, Y. H.; Zhu, W.; Peng, B.; Chen, Y. M.; Bai, R. Acta Polym. Sinica 2015, 6, 673. (孙立泷, 许韵华, 朱雯, 彭勃, 陈永明, 白茹, 高分子学报, 2015, 6, 673.)
[20] Espinosa, E.; Charleux, B.; D'Agosto, F.; Boisson, C.; Tripathy, R.; Faust, R.; Soulié-Ziakovic, C. Macromoleculars 2013, 46, 3417.
[21] Puskas, J. E.; Foreman-Orlowski, E. A.; Lim, G. T.; Porosky, S. E.; Evancho-Chapman, M. M.; Schmidt, S. P.; Fray, M. E.; Pi?tek, M.; Prowans, P.; Lovejoy, K. Biomaterials 2010, 31, 2477.
[22] Jewrajka, S. K.; Kang, J.; Erdodi, G.; Kennedy, J. P.;Yilgor, E.; Yilgor, I. J. Polym. Sc. Part A: Polym. Chem. 2009, 47, 2787.
[23] Herbst, F.; Seiffert, S.; Binder, W. H. Polym. Chem. 2012, 3, 3084.
[24] Ojha, U.; Kulkarni, P.; Singh, J.; Faust, R. J. Polym. Sci. Part A: Polym. Chem. 2009, 47, 3490.
[25] Kaszas, G.; Puskas, J. E.; Kennedy, J. P.; Hager, W. G. J. Polym. Sci. Part A: Polym. Chem. 1991, 29, 427.
[26] Storey, R. F.; Chisholm, B. J.; Lee, Y. Polym. Eng. Sci. 1997, 37, 73.
[27] Pinchuk, L.; Wilson, G. J.; Barry, J. J.; Schoephoerster, R. T.; Parel, J. M.; Kennedy, J. P. Biomaterials 2008, 29, 448.
[28] Cho, J. C.; Cheng, G. L.; Feng, D. S.; Faust, R.; Richard, R.; Schwarz, M.; Chan, K.; Boden, M. Biomacromolecules 2006, 7, 2997.
[29] Ojha, U.; Feng, D. S.; Chandekar, A.; Whitten, J. E.; Faust, R. Langmuir 2009, 25, 6319.
[30] Higashihara, T.; Faust, R. Macromolecules 2007, 40, 7453.
[31] Sipos, L.; Som, A.; Faust, R.; Richard, R.; Schwarz, M.; Ranade, S.; Boden, M.; Chan, K. Biomacromolecules 2005, 6, 2570.
[32] Malmsten, M.; Emoto, K.; Alstine, J. M. V. J. Colloid Interface Sci. 1998, 202, 507.
[33] Michel, R.; Pasche, S.; Textor, M.; Castner, D. G. Langmuir 2005, 21, 12327.
[34] Magenau, A. J. D.; Martinez-Castro, N.; Savin, D. A.; Storey, R. F. Macromolecules 2009, 42, 2353.
[35] Rother, M.; Barqawi, H.; Pfefferkorn, D.; Kressler, J.; Binder, W. H. Macromol. Chem. Phys. 2010, 211, 204.
[36] Gragert, M.; Schunack, M.; Binder, W. H. Macromol. Rapid Commun. 2011, 32, 419.
[37] Schunack, M.; Gragert, M.; Döhler, D.; Michael, P.; Binder, W. H. Macromol. Chem. Phys. 2012, 213, 205.
[38] Erdödi, G.; Iván, B. Chem. Mater. 2004, 16, 959.
[39] Schulz, M.; Tanner, S.; Barqawi, H.; Binder, W. H. J. Polym. Sci. Part A: Polym. Chem. 2010, 48, 671.
[40] Satoh, K.; Poelma, J. E.; Campos, L. M.; Stahl, B.; Hawker, C. J. Polym. Chem. 2012, 3, 1890.
[41] Wang, H. R.; He, J. L.; Zhang, M. Z.; Tao, Y. F.; Li, F.; Tam, K. C.; Ni, P. H. J. Mater. Chem. B 2013, 1, 6596.
[42] Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004.
[43] Wang, F.; Zhang, J. Q.; Ding, X.; Dong, S. Y.; Liu, M.; Zheng, B.; Li, S. J.; Wu, L.; Yu, Y. H.; Gibson, H. W.; Huang, F. H. Angew. Chem., Int. Ed. 2010, 49, 1090.
[44] Yan, X. Z.; Xu, D. H.; Chi, X. D.; Chen, J. Z.; Dong, S. Y.; Ding, X.; Yu, Y. H.; Huang, F. H. Adv. Mater. 2012, 24, 362.
[45] Ji, X. F.; Dong, S. Y.; Wei, P. F.; Xia, D. Y.; Huang, F. H. Adv. Mater. 2013, 25, 5725.
[46] Zhu, Y.; Storey, R. F. Macromolecules 2010, 43, 7048.
[47] Wang, H. C.; Zhang, M. Z.; Ni, P. H.; He, J. L.; Hao, Y.; Wu, Y. X. Chinese J. Polym. Sci. 2013, 31, 218.
[48] Hao, Y.; Zhang, Y.; He, J. L.; Shang, X. J.; Zhang, M. Z.; Ni, P. H. Acta Chim. Sinica 2014, 72, 569. (郝莹, 张洋, 何金林, 尚修娟, 张明祖, 倪沛红, 化学学报, 2014, 72, 569.)
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