Biodegradable Nanogel-Integrated Hydrogels for Sustained Protein Delivery

Asako Shimoda; Yuka Yamamoto; Shin-ichi Sawada; Kazunari Akiyoshi

Macromolecular Research, Vol.20, No.3, 266-270, March, 2012

DOI10.1007/s13233-012-0054-x Export Citation

Biodegradable Nanogel-Integrated Hydrogels for Sustained Protein Delivery

Asako Shimoda, Yuka Yamamoto, Shin-ichi Sawada¹, and Kazunari Akiyoshi^†

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan
¹Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan

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Polysaccharide nanogel-crosslinked hydrogels for sustained protein delivery systems were prepared using acryloyl group-modified cholesterol-bearing pullulan (CHPOA) as a building block and multiarmed poly(ethylene glycol) (PEGSH) with thiol groups as a cross-linker. Immobilized nanogels were released by the cleavage of ester bonds between the nanogels and cross-linkers according to environmental factors such as pH and the presence of serum. Fluorescein-isothiocyanate-labeled insulin (FITC-Ins)-containing hydrogel was prepared by the cross-linking of FITC-Ins-complexed nanogel and PEGSH. The protein-complexed nanogels were gradually released from the hydrogel by hydrolysis, and then the proteins in the nanogel were released by exchange reactions in the presence of bovine serum albumin. The CHPOA-PEGSH hydrogel is useful as a sustained protein delivery system.

Keywords:nanogel;polysaccharide;tissue engineering;hydrogel;sustained release.

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[1] Lee K, Silva EA, Mooney DJ, J. R. Soc. Interface., 8, 153 (2011)

[2] Mieszawska AJ, Kaplan DL, BMC Biology., 8, 59 (2010)

[3] Chen FM, Zhang M, Wu ZF, Biomaterials., 24, 6279 (2010)

[4] Silva AKA, Richard C, Bessodes M, Scherman D, Merten OW, Biomacromolecules, 10(1), 9 (2009)

[5] Yamamoto M, Takahashi Y, Tabata Y, Biomaterials., 24, 437 (2003)

[6] Spicer PP, Mikos AG, J. Control. Release., 48, 49 (2010)

[7] Getgood A, Brooks R, Fortier L, Rushton N, J. Bone Joint Surg. Br., 91, 565 (2009)

[8] Couet F, Rajan N, Mantovani D, Macromol. Biosci., 7, 701 (2007)

[9] Lin CC, Anseth KS, Adv. Funct. Mater., 19(14), 2325 (2009)

[10] Sasaki Y, Akiyoshi K, Chem. Rec., 10, 366 (2010)

[11] Rao JP, Geckeler KE, Prog. Polym. Sci., 36, 877 (2011)

[12] Akiyoshi K, Deguchi N, Moriguchi N, Yamaguchi S, Sunamoto J, Macromolecules., 26, 3062 (1993)

[13] Nishikawa T, Akiyoshi K, Sunamoto J, J. Am. Chem. Soc., 118(26), 6110 (1996)

[14] Akiyoshi K, Kobayashi S, Shichibe S, Mix D, Baudys M, Kim SW, Sunamoto J, J. Control. Release., 54, 313 (1998)

[15] Kageyama S, Kitano S, Hirayama M, Nagata Y, Imai H, Shiraishi T, Akiyoshi K, Scott AM, Murphy R, Hoffman EW, Old LJ, Katayama N, Shiku H, Cancer Sci., 99, 601 (2008)

[16] Nochi T, Yuki Y, Takahashi H, Sawada S, Mejima M, Kohda T, Harada N, Kong IG, Sato A, Kataoka N, Tokuhara D, Kurokawa S, Takahashi Y, Tsukada H, Kozaki S, Akiyoshi K, Kiyono H, Nat. Mater., 9(7), 572 (2010)

[17] Morimoto N, Endo T, Iwasaki Y, Akiyoshi K, Biomacromolecules, 6(4), 1829 (2005)

[18] Hasegawa U, Sawada S, Shimizu T, Kishida T, Otsuji E, Mazda O, Akiyoshi K, J. Control. Release., 140, 312 (2009)

[19] Shimoda A, Sawada S, Kano A, Maruyama A, Moquin A, Winnik FM, Akiyoshi K, Colloids Surf. B: Biointerfaces., in press.

[20] Kato N, Hasegawa U, Morimoto N, Saita Y, Nakashima K, Ezura Y, Kurosawa H, Akiyoshi K, Noda M, J. Cell Biochem., 101, 1063 (2007)

[21] Hayashi C, Hasegawa U, Saita Y, Hemmi H, Hayata T, Nakashima K, Ezura Y, Amagasa T, Akiyoshi K, Noda M, J. Cell Physiol., 220, 1 (2009)

[22] Kobayashi H, Katakura O, Morimoto N, Akiyoshi K, Kasugai S, J. Biomed. Mater. Res. B: Appl. Biomater., 91, 55 (2009)

[23] Kamolratanakul P, Hayata T, Ezura Y, Kawamata A, Hayashi C, Yamamoto Y, Hemmi H, Nagao M, Hanyu R, Notomi T, Nakamoto T, Amagasa T, Akiyoshi K, Noda M, Arthritis Rheum., 63, 1021 (2011)