Development and Physicochemical Evaluation of Chondroitin Sulfate-Poly(ethylene oxide) Hydrogel

다국어 초록 (Multilingual Abstract)

Novel chondroitin sulfate (CS) - poly(ethylene oxide) (PEO) hydrogel was synthesized and evaluated by a mechanism of self cross-linking of CS derivative with PEO with hexa-thiols (PEO-SH). A derivative of CS was synthesized by the sequential grafting of adipic acid dihydrazide (ADH) and acrylic acid: chemical grafting of ADH to the carboxylic acid in CS (CS-ADH) followed by grafting of the acrylic acid to the free amine groups in the CSADH (CS-ADH-Ac). The synthesis of CS-ADH-Ac molecules was confirmed by observing new acrylate peaks in CS-ADH-Ac by FTIR, ESCA, and NMR. The CS-PEO hydrogel was self cross-linked through a Michael type addition reaction between the acrylate end groups of CS-ADH-Ac and the thiol end groups of the PEO-SH. the gelation behavior of 10% CS-PEO was evaluated by rheological analyses from the changes in the solution properties, such as phase angles and visco-elasticities. Rheological analysis indicated that the gelation process was complete within 2 min after mixing two polymer solutions of CS-ADH-Ac and PEO-SH. The fabricated CS-PEO hydrogel was analyzed by measuring both its swelling under different water pHs and its mechanical strength against compression.
The morphological shapes of both its surface and cross sections were also evaluated after the sequential processes of gel swelling to equilibrium followed by dehydration. Both the gelation time and swelling of the fabricated hydrogel were dependent on the pH of the polymer solutions and swelling medium, showing quicker gel formation and better swelling behaviors under basic conditions than under acidic conditions. The equilibrated gel showed different morphologies depending on its location, i.e. its cross sections demonstrated more homogeneous morphologies than the surfaces. While the dehydrated hydrogel demonstrated 8-10 μm pore sizes on its cross sections, the compression strength of the hydrogel ranged from 1.4 to 2.8 Pa depending on its gel concentration. Toluidine blue molecules as a model drug were released from the hydrogel over a period of more than 5 days. These hydrogel properties, such as formation of in situ gel, release behaviors of toluidine blue, and porous structures and mechanical properties of the fabricated gel, highlighted the potential of a hydrogel as a carrier for local drug delivery and a scaffold for tissue engineering.

참고문헌 (Reference)

1 M. Lovu, 16 : 14-, 2008

2 O. Bruyere, 24 : 573-, 2007

3 I. Villanueva, 29 : 51-, 2010

4 R. J. Linhardt, 26 : 443-, 1995

5 A. Rebaudi, 23 : 371-, 2003

6 A. Rubinstein, 84 : 141-, 1992

7 A. P. Asimakopoulou, 22 : 385-, 2008

8 S. C. Wang, 329 : 103-, 2007

9 H. Cao, 19 : 567-, 2008

10 C. T. Lee, 7 : 2200-, 2006

11 B. Huang, 74 : 159-, 2009

12 J. F. Piai, 5 : 2601-, 2009

13 S. Varghese, 27 : 12-, 2008

14 L. Vodná, 7 : 629-, 2007

15 M. Brittberg, 331 : 889-, 1994

16 D. A. Grande, 7 : 208-, 1989

17 I. S. Kim, 50 : 553-, 2008

18 I. Noh, 83 : 674-, 2007

19 J. Kim, 19 : 3311-, 2008

20 L. F. Wang, 52 : 389-, 2003

21 D. A. Wang, 6 : 385-, 2007

22 M. F. Tsai, 84 : 727-, 2007

23 Gun-Woo Kim, "Synthesis and evaluation of hyaluronic acid？poly(ethylene oxide) hydrogel via Michael-type addition reaction" 한국물리학회 7 (7): 28-32, 2007

24 M. Balci, "Basic 1H-13C-NMR spectroscopy, 1st ed" Elsevier B. V 379-406, 2005