title: Synthesis, Characteristics and Potential Application of Poly(β-Amino Ester Urethane)-Based Multiblock Co-Polymers as an Injectable, Biodegradable and pH/Temperature-Sensitive Hydrogel System.
abstract: Physical polymeric hydrogels have significant potential for use as injectable depot drug/protein-delivery systems. In this study, a series of novel injectable, biodegradable and pH/temperature-sensitive multiblock co-polymer physical hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PEU) was synthesized by the polyaddition between the isocyanate groups of 1,6-diisocyanato hexamethylene and the hydroxyl groups of PEG and a synthesized monomer BTB (or ETE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized co-polymers were characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and gel-permeation chromatography. Aqueous solutions of the co-polymers showed a sol-to-gel phase transition with increasing pH and a gel-to-sol phase transition with increasing temperature. The gel regions covered the physiological conditions (37°C, pH 7.4) and could be controlled by changing the molecular weight of PEG, PEG/PEU ratio and co-polymer solution concentration. A gel formed rapidly in situ after injecting the co-polymer solution subcutaneously into SD rats and remained for more than 2 weeks in the body. The cytotoxicity tests confirmed the non-cytotoxicity of this co-polymer hydrogel. The controlled in vitro release of the model anticancer drug, doxorubicin, from this hydrogel occurred over a 7-day period. This hydrogel is a potential candidate for biomedical applications and drug/protein-delivery systems.
authors.affiliation: a Theranostic Macromolecules Research Center, Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Cong Truc
authors.initials: CT
authors.lastname: Huynh
authors.forename: Minh Khanh
authors.initials: MK
authors.lastname: Nguyen
authors.forename: In Ki
authors.initials: IK
authors.lastname: Jeong
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Doo Sung
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D065546:Drug Liberation; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007267:Injections; D008297:Male; D051379:Mice; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry; D011140:Polyurethanes / Q000737:chemistry*; D051381:Rats; D012212:Rheology; D013696:Temperature
chemical_list: D004337:Drug Carriers; D011140:Polyurethanes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D004317:Doxorubicin