Preparation and Biodegradation of Thermosensitive Chitosan Hydrogel as a Function of pH and Temperature

Hee Dong Han; Da Eun Nam; Dong Hoan Seo; Tae Woo Kim; Byung Cheol Shin; Ho Suk Choi

Macromolecular Research, Vol.12, No.5, 507-511, October, 2004

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Preparation and Biodegradation of Thermosensitive Chitosan Hydrogel as a Function of pH and Temperature

Hee Dong Han, Da Eun Nam, Dong Hoan Seo, Tae Woo Kim , Byung Cheol Shin^†, and Ho Suk Choi¹

Advanced Materials Division, Korea Research Institute of Chemical Technology, P.O. Box 107,Yuseong, Daejeon 305-606, Korea
¹Department of Chemical Engineering, Chungnam National University, 220 Gung, Yuseong, Daejeon 305-764, Korea

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We have developed an injectable thermosensitive hydrogel for local drug delivery to treat cancers clinically. We selected chitosan as a polymer matrix because of its biocompatibility and biodegradability. Glycerol 2-phosphate disodium salt hydrate (β-GP) was used to neutralize the chitosan solution to physiological pH. The chitosan solution displayed a sol-gel phase transition in a pH- and temperature-dependent manner and formed an endothermic hydrogel after subcutaneous injection into mouse in the presence of β-GP. Additionally, we evaluated the biodegradation of chitosan hydrogel in mice by measuring the volume of injected chitosan hydrogel after subcutaneous injection. The injected chitosan hydrogel in mice was sected and stained with hematoxylin-eosin reagent for histological observation to confirm biodegradation of the hydrogel by the infiltrated cells. Chitosan hydrogel systems that possess biocompatibility and biodegradability could be promising thermosensitive injectable materials useful as depot systems for local anti-cancer drug delivery.

Keywords:sol-gel transition;chitosan hydrogel;biodegradation

[References]

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Lee JW, Lee DS, Kim SW, Macromol. Res., 11(3), 189 (2003)
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Liu H, Mao J, Yao K, Yang G, Cui L, Cao Y, J. Biomater. Sci.-Polym. Ed., 15, 25 (2004)
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Ruel-Gariepy E, Chenite A, Chaput C, Guirguis S, Leroux JC, Int. J. Pharm., 203, 89 (2000)
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Ruel-Gariepy E, Shive M, Bichara A, Berrada M, Garrec DL, Chenite A, Leroux JC, Eur. J. Pharm. Biopharm., 57, 53 (2004)
Chenite A, Buschmann M, Wang D, Chaput C, Kandani N, Carbohydr. Polym., 46, 39 (2001)
Fujita M, Ishihara M, Simizu M, Obara K, Ishizuka T, Saito Y, Yura H, Morimoto Y, Takase B, Matsui T, Kikuchi M, Maehara T, Biomaterials, 25, 699 (2004)
Ma L, Cao C, Mao Z, Zhou J, Shen J, Hu X, Han C, Biomaterials, 24, 4833 (2003)

[Referenced By]

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[2] Ruel-Gariepy E, Leclair G, Hildgen P, Gupta A, Leroux JC, J. Control. Release, 82, 373 (2002)

[3] Francis Suh JK, Matthew HWT, Biomaterials, 21, 2589 (2000)

[4] Chenite A, Chaput C, Wang D, Combes C, Buschmann MD, Hoemann CD, Leroux JC, Atkinson BL, Binette F, Selmani A, Biomaterials, 21, 2155 (2000)

[5] Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997)

[6] Park YS, Han HD, Hong SU, Kim SS, Shin BC, Polym.(Korea), 28(1), 59 (2004)

[7] Lee JW, Lee DS, Kim SW, Macromol. Res., 11(3), 189 (2003)

[8] Lee SB, Seo SM, Lim YM, Cho SK, Lee YM, Macromol. Res., 12(3), 269 (2004)

[9] Berger J, Reist M, Mayer JM, Felt O, Pappas NA, Gurny R, Eur. J. Pharm. Biopharm., 57, 19 (2004)

[10] Berger J, Reist M, Mayer JM, Felt O, Gurny R, Eur. J. Pharm. Biopharm., 57, 35 (2004)

[11] Mi FL, Yan YC, Liang HF, Sung HW, Biomaterials, 23, 181 (2002)

[12] Paavola A, Kilpelainen I, Yliruusi J, Rosenberg P, Int. J. Pharm., 199, 85 (2000)

[13] Zhao HR, Wang K, Zhao Y, Pan LQ, Biomaterials, 23, 4459 (2002)

[14] Tomihata K, Ikada Y, Biomaterials, 18, 567 (1997)

[15] Liu H, Mao J, Yao K, Yang G, Cui L, Cao Y, J. Biomater. Sci.-Polym. Ed., 15, 25 (2004)

[16] Kofuji K, Akamine H, Qian CJ, Watanabe K, Togan Y, Nishimura M, Sugiyama I, Murata Y, Kawashima S, Int. J. Pharm., 272, 65 (2004)

[17] Ruel-Gariepy E, Chenite A, Chaput C, Guirguis S, Leroux JC, Int. J. Pharm., 203, 89 (2000)

[18] Unezaki S, Maruyama K, Hosoda JI, Nagae I, Koyanagi Y, Nakata M, Ishida O, Iwatsuru M, Tsuchiya S, Int. J. Pharm., 144, 11 (1996)

[19] Ruel-Gariepy E, Shive M, Bichara A, Berrada M, Garrec DL, Chenite A, Leroux JC, Eur. J. Pharm. Biopharm., 57, 53 (2004)

[20] Chenite A, Buschmann M, Wang D, Chaput C, Kandani N, Carbohydr. Polym., 46, 39 (2001)

[21] Fujita M, Ishihara M, Simizu M, Obara K, Ishizuka T, Saito Y, Yura H, Morimoto Y, Takase B, Matsui T, Kikuchi M, Maehara T, Biomaterials, 25, 699 (2004)

[22] Ma L, Cao C, Mao Z, Zhou J, Shen J, Hu X, Han C, Biomaterials, 24, 4833 (2003)