Controlling the Degradation of pH/Temperature-Sensitive Injectable Hydrogels Based on Poly(beta-amino ester)

Dai Phu Huynh; Minh Khanh Nguyen; Doo Sung Lee

Macromolecular Research, Vol.18, No.2, 192-199, February, 2010

DOI10.1007/s13233-009-0182-0 Export Citation

Controlling the Degradation of pH/Temperature-Sensitive Injectable Hydrogels Based on Poly(beta-amino ester)

Dai Phu Huynh, Minh Khanh Nguyen, and Doo Sung Lee^†

Department of Polymer Science and Engineering, SungKyunKwan University, Gyeonggi, 440-746, Korea

E-mail:

Poly (ethylene glycol) (PEG) -poly(epsilon-caprolactone(CL)-co-D,L-lactide (LA)) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form a temperature sensitive hydrogel triblock copolymer. Poly(beta-amino ester) (PAE) obtained from 1,4-butanediol diacrylate (BDA), and 4,4'-trimethylene dipiperidine ( TMDP) was used as a pH sensitive moiety to conjugate to the triblock copolymer. The physicochemical properties of the temperature-sensitive triblock and pH/temperature-sensitive pentablock copolymers (PAE-PCLA-PEG-PCLA-PAE) were characterized by H-1 NMR spectroscopy and gel permeation spectroscopy. The sol-gel phase transition behavior of the PAE-PCLA-PEG-PCLA-PAE block copolymers was investigated. An aqueous solution of the copolymers (20 wt%) changed from a sol phase at pH 6.4 and 10 degrees C to a gel phase at pH 7.4 and 37 degrees C. In addition, the degradation of PAE-PCLA-PEG-PCLA-PAE was compared with that of poly(ethylene glycol) -poly(epsilon-caprolactone) - poly (beta-amino ester) (PAE-PCL-PEG-PCL-PAE) using both in vitro and in vivo experiments. The relationship between the insulin release profile from the matrix and the degradation of these materials also investigated.

Keywords:biodegradable hydrogel;pH/temperature sensitive;beta-amino ester

[References]

American Diabetes Association, National Diabetes Fact Sheet. www.diabetes.org, 2004 (October 5).
Tyagi P, Indian J. Pharmacol., 34, 379 (2002)
Wang J, Tabata Y, Morimoto K, J. Control. Release, 113, 31 (2006)
Morishita M, Goto T, Peppas NA, Joseph JI, Torjman MC, Munsick C, Nakamura K, Takayama K, Lowman AM, J. Control. Release, 97, 115 (2004)
Chiou GCY, U.S. Patent 5283236 (1992).
Tobio M, Gref R, Sanchez A, Langer R, Alonso M, J. Pharm. Res., 15, 270 (1998)
Soma CE, Dubernet C, Barratt G, Nemati F, Appel M, Benita S, Couvreur P, Pharm. Res., 16, 1710 (1999)
Cammas S, Suzuki K, Sone C, Sakurai Y, Kataoka K, Okano T, J. Control. Release, 48, 157 (1997)
Kataoka K, Kwon GS, Yokoyama M, Okano T, Sakurai Y, J. Control. Release, 24, 1190 (1993)
Qiao M, Chen D, Ma X, Liu Y, Int. J. Pharm., 294, 103 (2005)
Hoffman AS, Adv. Drug Deliv. Rev., 3, 53 (2002)
Cohn D, Stern S, Gonzalez MF, Epstein J, J. Biomed. Mater. Res., 59, 273 (2002)
Zhao SP, Zhang LM, Ma D, J. Phys. Chem. B, 110(25), 12225 (2006)
Huang X, Lowe TL, Biomacromolecules, 6(4), 2131 (2005)
Yang YW, Yang Z, Zhou ZK, Attwood D, Booth C, Macromolecules, 29(2), 670 (1996)
Akinc A, Anderson DG, Lynn DM, Langer R, Bioconjugate Chem., 14, 979 (2003)
Little SR, Lynn DM, Langer R, Proc. National Acad. Sci. USA, 101, 9534 (2004)
Berry D, Lynn DM, Sasisekharan R, Langer R, Chem. Biology, 11, 487 (2004)
Kim MS, Lee DS, Choi EK, Park HJ, Kim JS, Macromol. Res., 13(2), 147 (2005)
Huynh DP, Nguyen MK, Pi BS, Kim MS, Chae SY, Lee KC, Kim BS, Lee SW, Lee DS, Biomaterials, 29, 2527 (2008)
Huynh DP, Nguyen MK, Kim BS, Lee DS, Polymer, 50(12), 2565 (2009)
Huynh DP, Im GJ, Chae SY, Lee KC, Lee DS, J. Control. Release, 137, 20 (2009)
Stevens MG, Olsen S, J. Immunol. Methods, 157, 225 (1993)
Shim WS, Yoo JS, Bae YH, Lee DS, Biomacromolecules, 6(6), 2930 (2005)
Huynh DP, Shim WS, Kim JH, Lee DS, Polymer, 47(23), 7918 (2006)

[Referenced By]

[Related Articles]

[1] American Diabetes Association, National Diabetes Fact Sheet. www.diabetes.org, 2004 (October 5).

[2] Tyagi P, Indian J. Pharmacol., 34, 379 (2002)

[3] Wang J, Tabata Y, Morimoto K, J. Control. Release, 113, 31 (2006)

[4] Morishita M, Goto T, Peppas NA, Joseph JI, Torjman MC, Munsick C, Nakamura K, Takayama K, Lowman AM, J. Control. Release, 97, 115 (2004)

[5] Chiou GCY, U.S. Patent 5283236 (1992).

[6] Tobio M, Gref R, Sanchez A, Langer R, Alonso M, J. Pharm. Res., 15, 270 (1998)

[7] Soma CE, Dubernet C, Barratt G, Nemati F, Appel M, Benita S, Couvreur P, Pharm. Res., 16, 1710 (1999)

[8] Cammas S, Suzuki K, Sone C, Sakurai Y, Kataoka K, Okano T, J. Control. Release, 48, 157 (1997)

[9] Kataoka K, Kwon GS, Yokoyama M, Okano T, Sakurai Y, J. Control. Release, 24, 1190 (1993)

[10] Qiao M, Chen D, Ma X, Liu Y, Int. J. Pharm., 294, 103 (2005)

[11] Hoffman AS, Adv. Drug Deliv. Rev., 3, 53 (2002)

[12] Cohn D, Stern S, Gonzalez MF, Epstein J, J. Biomed. Mater. Res., 59, 273 (2002)

[13] Zhao SP, Zhang LM, Ma D, J. Phys. Chem. B, 110(25), 12225 (2006)

[14] Huang X, Lowe TL, Biomacromolecules, 6(4), 2131 (2005)

[15] Yang YW, Yang Z, Zhou ZK, Attwood D, Booth C, Macromolecules, 29(2), 670 (1996)

[16] Akinc A, Anderson DG, Lynn DM, Langer R, Bioconjugate Chem., 14, 979 (2003)

[17] Little SR, Lynn DM, Langer R, Proc. National Acad. Sci. USA, 101, 9534 (2004)

[18] Berry D, Lynn DM, Sasisekharan R, Langer R, Chem. Biology, 11, 487 (2004)

[19] Kim MS, Lee DS, Choi EK, Park HJ, Kim JS, Macromol. Res., 13(2), 147 (2005)

[20] Huynh DP, Nguyen MK, Pi BS, Kim MS, Chae SY, Lee KC, Kim BS, Lee SW, Lee DS, Biomaterials, 29, 2527 (2008)

[21] Huynh DP, Nguyen MK, Kim BS, Lee DS, Polymer, 50(12), 2565 (2009)

[22] Huynh DP, Im GJ, Chae SY, Lee KC, Lee DS, J. Control. Release, 137, 20 (2009)

[23] Stevens MG, Olsen S, J. Immunol. Methods, 157, 225 (1993)

[24] Shim WS, Yoo JS, Bae YH, Lee DS, Biomacromolecules, 6(6), 2930 (2005)

[25] Huynh DP, Shim WS, Kim JH, Lee DS, Polymer, 47(23), 7918 (2006)