Biodegradable pH- and Temperature-Sensitive Multiblock Copolymer Hydrogels Based on Poly(amino-ester urethane)s

다국어 초록 (Multilingual Abstract)

A novel pH- and temperature-responsive multiblock copolymer consisting of poly(ethylene glycol) (PEG) and poly(amino-ester urethane) (PAEU) is reported. First, a biodegradable monomer, bis-1,4-(hydroxyethyl)piperazine mono-lactate (HEP mono-lactate), was synthesized by the ring-opening polymerization of D,L-lactide (LA) using HEP and Sn(Oct)2 as an initiator and catalyst, respectively. The multiblock copolymers were synthesized further from PEG, HEP, HEP mono-lactate, and 1,6-diisocyanatohexamethylene (HDI) in the presence of dibutyltin dilaurate as a catalyst.
The resulting copolymers were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). At pH 6.8 or higher, the copolymer aqueous solutions showed gel-to-sol transitions with increasing temperature, and the gel window covered the physiological conditions. After a subcutaneous injection of the multiblock copolymer solution into SD rats, a soft gel was formed in a short time. The degradability of the copolymer was adjusted by varying the LA content in the PAEU block.

참고문헌 (Reference)

1 E. S. Gil, 29 : 1173-, 2004

2 K. Dayananda, 48 : 758-, 2007

3 X. Jia, 25 : 4797-, 2004

4 J. A. Burdick, 6 : 386-, 2005

5 J. S. Temenoff, 21 : 2405-, 2000

6 B. Jeong, 54 : 79-, 2002

7 C. L. He, 127 : 189-, 2008

8 H. Colfen, 22 : 219-, 2001

9 K. Dayananda, 49 : 4968-, 2008

10 J. L. Thomas, 117 : 2949-, 1995

11 K. Y. Chen, 21 : 161-, 2000

12 J. M. Suh, 17 : 118-, 2005

13 C. Hiemstra, 119 : 320-, 2007

14 X. J. Loh, 8 : 585-, 2007

15 C. L. He, 29 : 490-, 2008

16 S. Y. Park, 28 : 1172-, 2007

17 N. Stavrouli, 29 : 130-, 2008

18 Y. Hu, 85 : 705-, 2004

19 S. H. Yuk, 30 : 6856-, 1997

20 H. Feil, 25 : 5528-, 1992

21 W. S. Shim, 6 : 2930-, 2005

22 D. P. Huynh, 47 : 7918-, 2006

23 Su Jong Hwang, "pH-Sensitivity Control of PEG-Poly(β-Amino ester) Block Copolymer Micelle" 한국고분자학회 15 (15): 437-442, 2007

24 배진우, "Thermosensitive Chitosan as an Injectable Carrier for Local Drug Delivery" 한국고분자학회 14 (14): 461-465, 2006

25 Mehrdad Mahkam, "Synthesis and Characterization of Novel pH-Sensitive Hydrogels Containing Ibuprofen Pendents for Colon-Specific Drug Delivery" 한국고분자학회 17 (17): 709-713, 2009

26 Kasala Dayana, "Synthesis and Characterization of MPEG-b-PDPA Amphiphilic Block Copolymer via Atom Transfer Radical Polymerization and Its pH-Dependent Micellar Behavior" 한국고분자학회 15 (15): 385-391, 2007

27 Sanping Zhao, "Synthesis and Characterization of Biodegradable Thermo- and pH-Sensitive Hydrogels Based on Pluronic F127/Poly(ε-caprolactone) Macromer and Acrylic Acid" 한국고분자학회 17 (17): 1025-1031, 2009

28 홍광현, "Preparation and Properties of Modified PHEMA Hydrogels Containing Thermo-responsive Pluronic Component" 한국고분자학회 17 (17): 26-30, 2009

29 N. M. K. Lamba, "Polyurethanes in biomedical applications" CRS Press 1998

30 Kasala Dayananda, "MPEG-b-Poly(amino urethane) Amphiphilic Block Copolymers and Their pH-Dependent Micellization Behavior" 한국고분자학회 17 (17): 58-61, 2009

31 전여진, "In situ Gel Forming Stereocomplex Composed of Four-Arm PEG-PDLA and PEG-PLLA Block Copolymers" 한국고분자학회 16 (16): 704-710, 2008

32 N. A. Peppas, "Hydrogels in Medicine and Pharmacy" CRC Press, 1987

33 이재성, "Formation of Poly(ethylene glycol)-Poly(ε-caprolactone) Nanoparticles via Nanoprecipitation" 한국고분자학회 17 (17): 72-78, 2009

34 한종권, "Evaluation of the Anti-Tumor Effects of Paclitaxel-Encapsulated pH-Sensitive Micelles" 한국고분자학회 17 (17): 99-103, 2009

35 Dai Phu Huynh, "Controlling the Degradation of pH/Temperature-Sensitive Injectable Hydrogels Based on Poly(β-amino ester)" 한국고분자학회 18 (18): 192-199, 2010

36 김지흥, "Biodegradable Thermo- and pH-Responsive Hydrogels Based on Amphiphilic Polyaspartamide Derivatives Containing N,N-Diisopropylamine Pendants" 한국고분자학회 16 (16): 489-491, 2008