Abstract
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.
Highlights
Recent advances in protein therapeutics have garnered increasing attention for the treatment of various debilitating diseases[1]
PH-/temperature-sensitive PEG-PACU copolymer was synthesized by the polyaddition polymerization reaction of hexamethylene diisocyanate (HDI) with HEP-trimethylene carbonate (TMC) and PEG-diols
The human growth hormone (hGH) released from the injectable hydrogel was appeared at an identical retention time. These results indicated that hGH released from PEG-PACU-based injectable hydrogels was in its native state
Summary
Recent advances in protein therapeutics have garnered increasing attention for the treatment of various debilitating diseases[1]. The major advantages of injectable hydrogels are as follows: the high moldability because of their ability to form a desired shape at the defect site that is coherent with the surrounding tissues, the easy administration of gels to inaccessible sites because of their low viscosity, and in vivo delivery in a minimal invasive manner because of their small scar size formation during administration with less pain for patients[17,21,22]. The biocompatibility shortcoming has been surmounted using poly(ester)-based copolymers, which exhibit an ideal phase transition and biodegradability, the generation of acidic degradation products further limits their application in vivo. We developed biodegradable, cationic and injectable hydrogels composed of poly(ethylene glycol)-poly(amino carbonate urethane) (PEG-PACU) for the sustained delivery of hGH, a negatively charged model protein. The in vivo gelation and the protein release behavior were evaluated in male Sprague-Dawley (SD) rats
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