Macromolecular Research

The Polymer Society of Korea (한국고분자학회)
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Preparation of Thermo-Responsive and Injectable Hydrogels Based on Hyaluronic Acid and Poly(N-isopropylacrylamide) and Their Drug Release Behaviors

  • Ha Dong In (School of Chemical Engineering, College of Engineering, Hanyang University) ;
  • Lee Sang Bong (School of Chemical Engineering, College of Engineering, Hanyang University) ;
  • Chong Moo Sang (School of Chemical Engineering, College of Engineering, Hanyang University) ;
  • Lee Young Moo (School of Chemical Engineering, College of Engineering, Hanyang University) ;
  • Kim So Yeon (Nanomaterials Application Division, Korea Institute of Ceramic Engineering and Technology) ;
  • Park Young Hoon (Department of Polymer Engineering, Sunchon National University)
  • Published : 2006.02.01
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Abstract

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications. Semi-telechelic PNIPAAm, with amino groups at the end of each main chain, was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent, and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry. The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30$\∼$33$^{circ}C$. As the graft yield of PNIPAAm onto the HA backbone increased, the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition. The short chain PNIPAAm-grafted HA ($M_{w}$=6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA ($M_{w}$=13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35$^{circ}C$, thus allowing the gels to maintain their shape for 24 h after in vivo administration. From the in vitro riboflavin release study, the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased. In addition, BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit, followed by a sustained release profile after 60 h.

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References

  1. A. S. Hoffman, Adv. Drug Deliver. Rev., 43, 3 (2002)
  2. J. A. Hubbell, Curr. Opin. Solid St. M., 3, 246 (1998) https://doi.org/10.1016/S1359-0286(98)80098-3
  3. L. G. Griffith, Acta Materialia, 48, 263 (2000) https://doi.org/10.1016/S1359-6454(99)00299-2
  4. A. Gutowska, B. Jeong, and M. Jasionowski, The Anatomical Record, 263, 342 (2001) https://doi.org/10.1002/ar.1115
  5. S. Kim and K. E. Healy, Biomacromolecules, 4, 1214 (2003) https://doi.org/10.1021/bm0340467
  6. T. A. Holland, Y. Tabata, and A. G. Mikos, J. Control. Release, 91, 299 (2003) https://doi.org/10.1016/S0168-3659(03)00258-X
  7. S. R. Van Tomme, M. J. van Steenbergen, S. C. De Smedt, C. F. van Nostrum, and W. E. Hennink, Biomaterials, 26, 2129 (2005) https://doi.org/10.1016/j.biomaterials.2004.05.035
  8. X. Z. Shu, Y. Liu, F. S. Palumbo, Y. Luo, and G. D. Prestwich, Biomaterials, 25, 1339 (2004) https://doi.org/10.1016/j.biomaterials.2003.08.014
  9. S. Cai, Y. Liu, X. Z. Shu, and G. D. Prestwich, Biomaterials, 26, 6054 (2005) https://doi.org/10.1016/j.biomaterials.2005.03.012
  10. K. Y. Cho, T. W. Chung, B. C. Kim, M. K. Kim, J. H. Lee, W. R. Wee, and C. S. Cho, J. of Pharmaceutics, 260, 83 (2003) https://doi.org/10.1016/S0378-5173(03)00259-X
  11. A. Chenite, C. Chaput, D. Wang, C. Combes, M. D. Buschmann, C. D. Hoemann, J. C. Leroux, B. L. Atkinson, F. Binette, and A. Selmani, Biomaterials, 21, 2155 (2000) https://doi.org/10.1016/S0142-9612(00)00116-2
  12. J. L. West and J. A. Hubbell, Macromolecules, 32, 241 (1999) https://doi.org/10.1021/ma981296k
  13. B. K. Mann, A. S. Gobin, A. T. Tsai, R. H. Schmedlen, and J. L. West, Biomaterials, 22, 3045 (2001) https://doi.org/10.1016/S0142-9612(01)00051-5
  14. Y. D. Park, N. Tirelli, and J. A. Hubbell, Biomaterials, 24, 893 (2003) https://doi.org/10.1016/S0142-9612(02)00420-9
  15. H. G. Schild, Prog. Polym. Sci., 17, 163 (1992)
  16. R. Yoshida, K. Sakai, T. Okano, and Y. Sakurai, J. Biomat. Sci.-Polym. E, 6, 585 (1994)
  17. T. Inoue, G. Chen, K. Nakamae, and A. S. Hoffman, Polym. Gels Netw., 5, 561 (1997) https://doi.org/10.1016/S0966-7822(97)00029-4
  18. M. Ebara, T. Aoyagi, K. Sakai, and T. Okano, Macromolecules, 33, 8312 (2000) https://doi.org/10.1021/ma000121j
  19. J. Zhang and N. A. Peppas, Macromolecules, 33, 102 (2000) https://doi.org/10.1021/ma991398q
  20. G. Chen and A. S. Hoffman, Bioconjugat. Chem., 4, 509 (1993) https://doi.org/10.1021/bc00024a013
  21. Y. Kaneko, K. Sakai, A. Kikuchi, R. Yoshida, Y. Sakurai, and T. Okano, Macromolecules, 28, 7717 (1995) https://doi.org/10.1021/ma00127a018
  22. Y. Kanejo, S. Nakamura, K. Sakai, A. Kikuchi, T. Aoyagi, and T. Okano. Polym. Gels Netw., 6, 333 (1988) https://doi.org/10.1016/S0966-7822(98)00022-7
  23. S. Ohya, H. Sonoda, Y. Nakayama, and T. Matsuda, Biomaterials, 26, 655 (2005) https://doi.org/10.1016/j.biomaterials.2004.03.002
  24. H. K. Ju, S. Y. Kim, S. J. Kim, and Y. M. Lee, J. Appl. Polym. Sci., 83, 1128 (2002) https://doi.org/10.1002/app.10137
  25. H. K. Ju, S. Y. Kim, and Y. M. Lee, Polymer, 42, 6851 (2001) https://doi.org/10.1016/S0032-3861(01)00143-4
  26. J. H. Kim, S. B. Lee, S. J. Kim, and Y. M. Lee, Polymer, 43, 7549 (2002) https://doi.org/10.1016/S0032-3861(02)00675-4
  27. M. R. Kim and T. G. Park, J. Control. Release, 80, 69 (2002) https://doi.org/10.1016/S0168-3659(01)00557-0
  28. K. Pietrucha, Int. J. Biol. Macromol., 36, 299 (2005) https://doi.org/10.1016/j.ijbiomac.2005.07.004
  29. S.Y. Kim, S. M. Cho, Y. M. Lee, and S. J. Kim, J. Appl. Polym. Sci., 78, 1381 (2000) https://doi.org/10.1002/1097-4628(20001114)78:7<1381::AID-APP90>3.0.CO;2-M
  30. Y. C. Bae, S. M. Lander, D. S. Soane, and M. Prauzsnitz, Macromolecules, 24, 4403 (1991) https://doi.org/10.1021/ma00015a024
  31. H. Liu, Y. Yin, K. Yao, D. Ma, L. Cui, and Y. Cao, Biomaterials, 25, 3523 (2004) https://doi.org/10.1016/j.biomaterials.2003.09.102