Controlled release of human growth hormone from a biodegradable pH/temperature-sensitive hydrogel system

Biodegradable pH/temperature-sensitive triblock copolymer hydrogels composed of poly(ethylene glycol) (PEG) and poly(beta-amino ester urethane) (PAEU) were synthesized and characterized. The presence of urethane and tertiary amine groups in the synthesized copolymers could enhance the hydrogen bonds and ionic interactions between copolymers and drug/protein molecules, particularly the anionic-type. The existence of a copolymer solution at low pH and low temperatures (e.g. 20 degrees C, pH 6.0) facilitates the formulation of a hydrogel precursor with therapeutic agents, while the transition to the gel state at the physiological conditions (37 degrees C, pH 7.4) provides the potential application as a drug/protein carrier. The non-cytotoxicity of this hydrogel system was confirmed by the in vitro cytotoxicity test. The release of human growth hormone (hGH) from this hydrogel system was controlled for more than 5 days in vitro and 3 days in vivo without an initial burst, exhibiting the potential application as a protein carrier.