Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Chemoenzymatic Synthesis of Dual-responsive Amphiphilic Block Copolymers and Drug Release Studies

  • Chen, Peng (Alan G. MacDiarmid Institute of Jilin University) ;
  • Li, Ya-Peng (Alan G. MacDiarmid Institute of Jilin University) ;
  • Wang, Shu-Wei (Alan G. MacDiarmid Institute of Jilin University) ;
  • Meng, Xin-Lei (Alan G. MacDiarmid Institute of Jilin University) ;
  • Zhu, Ming (Alan G. MacDiarmid Institute of Jilin University) ;
  • Wang, Jing-Yuan (Alan G. MacDiarmid Institute of Jilin University)
  • Received : 2012.12.03
  • Accepted : 2013.03.24
  • Published : 2013.06.20
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Abstract

Dual-responsive amphiphilic block copolymers were synthesized by combining enzymatic ring-opening polymerization (eROP) of ${\varepsilon}$-caprolactone (CL) and ATRP of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). The obtained block copolymers were characterized by gel permeation chromatography (GPC), $^1H$ NMR and FTIR-IR. The critical micelle concentration (CMC) of copolymer was determined by fluorescence spectra, it can be found that with hydrophilic block (PDMAEMA) increasing, CMC value of the polymer sample increased accordingly, and the CMC value was 0.012 mg/mL, 0.025 mg/mL and 0.037 mg/mL for $PCL_{50}$-b-$PDMAEMA_{68}$, $PCL_{50}$-b-$PDMAEMA_{89}$, $PCL_{50}$-b-$PDMAEMA_{112}$, $PCL_{50}$-b-$PDMAEMA_{89}$ was chosen as drug carrier to study in vitro release profile of anti-cancer drug (taxol). The temperature and pH dependence of the values of hydrodynamic diameter (Dh) of micelles, and self-assembly of the resulting block copolymers in water were evaluated by dynamic light scattering (DLS). The result showed that with the temperature increasing and pH decreasing, the Dh decreased. Drug-loaded nanoparticles were fabricated using paclitaxel as model. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) had been explored to study the morphology of the hollow micelles and the nanoparticles, revealing well-dispersed spheres with the average diameters both around 80 nm. In vitro release kinetics of paclitaxel from the nanoparticles was also investigated in different conditions (pH and temperature, etc.), revealing that the drug release was triggered by temperature changes upon the lower critical solution temperature (LCST) at pH 7.4, and at $37^{\circ}C$ by an increase of pH.

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References

  1. Adam, W.; Stacey, E.; Charles, L. Adv. Drug. Delivery. Rev. 2008, 60, 1018. https://doi.org/10.1016/j.addr.2008.02.006
  2. Mertoglu M.; Garnier S.; Laschewsky A. Polymer 2005, 46, 7726. https://doi.org/10.1016/j.polymer.2005.03.101
  3. Tonhauser, C.; Golriz, A. A.; Moers, C. Adv. Mater. 2012, 24, 5559. https://doi.org/10.1002/adma.201202105
  4. Ray, J. G.; Naik, S. S.; Hoff, E. A. Macromol. Rapid Commun. 2012, 33, 819. https://doi.org/10.1002/marc.201100881
  5. Ganta, S.; Devalapally, H.; Shahiwala, A. J. Controlled Release. 2008, 126, 187. https://doi.org/10.1016/j.jconrel.2007.12.017
  6. Nishiyama, N.; Bae, Y.; Miyata, K. Drug Discovery Today: Technologies 2005, 2, 21. https://doi.org/10.1016/j.ddtec.2005.05.007
  7. Gao, Z.; Eisenberg, A. Macromolecules 1993, 26, 7353. https://doi.org/10.1021/ma00078a035
  8. Meng, F.; Zhong, Z.; Feijen, J. Biomacromolecules 2009, 10, 197. https://doi.org/10.1021/bm801127d
  9. Zhang, W.; Shi, L.; Ma, R. Macromolecules 2005, 38, 8850. https://doi.org/10.1021/ma050998o
  10. Hu, Z.; Xia, X. Adv. Mater. 2004, 16, 305. https://doi.org/10.1002/adma.200305560
  11. Isojima, T.; Lattuada, M.; Alan Hatton, T. ACS Nano 2008, 2, 1799. https://doi.org/10.1021/nn800089z
  12. Plamper, F. A.; Ruppel, M.; Müller, A. H. E. Macromolecules 2007, 40, 8361. https://doi.org/10.1021/ma071203b
  13. WellsF, A. Org. Process Res. Dev. 2006, 10, 681.
  14. Scarpello, J. T.; Nair, D.; Freitas dos Santos, L. M. J. Membr. Sci. 2002, 203, 71. https://doi.org/10.1016/S0376-7388(01)00751-7
  15. Torque, C.; Bricout, H.; Hapiot, F. Tetrahedron 2004, 60, 6487. https://doi.org/10.1016/j.tet.2004.06.028
  16. Lopez-Gallego, F.; Betancor, L.; Hidalgo, A. J. Biotechnol. 2004, 111, 219 . https://doi.org/10.1016/j.jbiotec.2004.04.006
  17. Van Beilen, J. B.; Li, Z. Curr. Opin. Biotechnol. 2002, 13, 338. https://doi.org/10.1016/S0958-1669(02)00334-8
  18. Murakami, Y.; Hoshi, R.; Hirata, A. J. Mol. Catal. B: Enzym. 2003, 22, 79. https://doi.org/10.1016/S1381-1177(03)00009-2
  19. Ivanov, A. E.; Edink, E.; Kumar, A. Biotechnol. Progr. 2003, 19, 1167.
  20. Konwarh, R.; Kalita, D.; Mahanta, C. Appl. Microbiol. Biotechnol. 2010, 87, 1983. https://doi.org/10.1007/s00253-010-2658-4
  21. Yoshida, T.; Seno, K. I.; Kanaoka, S. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 1155. https://doi.org/10.1002/pola.20589
  22. Aoshima, S.; Sugihara, S.; Shibayama, M. Macromol. Symp. 2004, 215, 151. https://doi.org/10.1002/masy.200451113
  23. Aoshima, S.; Sugihara, S. J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 3962. https://doi.org/10.1002/1099-0518(20001101)38:21<3962::AID-POLA130>3.0.CO;2-9
  24. Ruckenstein, E.; Zhang, H. M. Macromolecules 1998, 31, 9127. https://doi.org/10.1021/ma9812534
  25. Hirao, A.; Hayashi, M.; Haraguchi, N. Macromol. Rapid Commun. 2000, 21, 1171. https://doi.org/10.1002/1521-3927(20001101)21:17<1171::AID-MARC1171>3.0.CO;2-C
  26. Hirao, A.; Higashihara, T.; Inoue, K. Macromolecules 2008, 41, 3579. https://doi.org/10.1021/ma800146p
  27. Cunningham, M. F. Prog. Polym. Sci. 2008, 33, 365. https://doi.org/10.1016/j.progpolymsci.2007.11.002
  28. Matyjaszewski, K.; Spanswick, J. Materialstoday 2005, 8, 26.
  29. Yamago, S.; Iida, K.; Yoshida, J. I. J. Amer. Chem. Soc. 2002, 124, 2874. https://doi.org/10.1021/ja025554b
  30. Coessens, V.; Pintauer, T.; Matyjaszewski, K. Progress in Polymer Science 2001, 26, 337. https://doi.org/10.1016/S0079-6700(01)00003-X
  31. Tsarevsky, N. V.; Matyjaszewski, K. Chem. Rev. 2007, 107, 2270. https://doi.org/10.1021/cr050947p
  32. Licciardi, M.; Tang, Y.; Billingham, N. C. Biomacromolecules 2005, 6, 1085. https://doi.org/10.1021/bm049271i
  33. Li, C. Z.; Benicewicz, B. C. Macromolecules 2005, 38, 5929. https://doi.org/10.1021/ma050216r
  34. Lowe, A. B.; McCormick, C. L. Prog. Polym. Sci. 2007, 3, 283.
  35. Cho, J. C.; Cheng, G. L.; Feng, D. S. Biomacromolecules 2006, 7, 2997. https://doi.org/10.1021/bm0604496
  36. Prabaharan, M.; Grailer, J. J.; Pilla, S. Biomaterials 2009, 30, 6065. https://doi.org/10.1016/j.biomaterials.2009.07.048
  37. Blanazs, A.; Armes, S. P.; Ryan, A. J. Macromol. Rapid Commun. 2009, 30, 267. https://doi.org/10.1002/marc.200800713
  38. Kwon, G. S.; Forrest, M. L. Drug Dev. Res. 2006, 67, 15. https://doi.org/10.1002/ddr.20063
  39. Meyer, U.; Palmans, A. R. A.; Loontjens, T. Macromolecules 2002, 35, 2873. https://doi.org/10.1021/ma011929m
  40. Sha, K.; Qin, L.; Li, D. S. Poly Bull. 2005, 54, 1. https://doi.org/10.1007/s00289-005-0341-1
  41. Sha, K.; Li, D. S.; Li, Y. P. Macromolecules 2008, 41, 361. https://doi.org/10.1021/ma0707234
  42. Wang, W.; Li, Y. P.; Zhao, Y. L. Acta Polymerica Sinica 2010, 2, 199.