Poly(amino carbonate urethane)-based biodegradable, temperature and pH-sensitive injectable hydrogels for sustained human growth hormone delivery

In this study, a new pH-/temperature-sensitive, biocompatible, biodegradable, and injectable hydrogel based on poly(ethylene glycol)-poly(amino carbonate urethane) (PEG-PACU) copolymers has been developed for the sustained delivery of human growth hormone (hGH). In aqueous solutions, PEG-PACU-based copolymers existed as sols at low pH and temperature (pH 6.0, 23 °C), whereas they formed gels in the physiological condition (pH 7.4, 37 °C). The physicochemical characteristics, including gelation rate, mechanical strength and viscosity, of the PEG-PACU hydrogels could be finely tuned by varying the polymer weight, pH and temperature of the copolymer. An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel, which exhibited a homogenous porous structure. In addition, an in vivo biodegradation study of the PEG-PACU hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site and the surrounding tissue. The hGH-loaded PEG-PACU copolymer solution readily formed a hydrogel in SD rats, which subsequently inhibited the initial hGH burst and led to the sustained release of hGH. Overall, the PEG-PACU-based copolymers prepared in this study are expected to be useful biomaterials for the sustained delivery of hGH.