Novel pH-sensitive hydrogels with peg-tethered chains for oral delivery of calcitonin

摘要

Major challenges in oral delivery of peptides include the need to overcome gastric and intestinal degradation. pH -Sensitive hydrogels are suitable candidates for oral drug delivery of peptides due to their ability to respond to their environment. We have developed a new type of hydrogel composed of poly(methacrylic acid) grafted with poly(ethylene glycol) which can be used as drug delivery carriers for salmon calcitonin. These hydrogels were prepared by free radical solution polymerization and were molecularly designed to contain poly(ethylene glycol) tethered chains promoting mucosal adhesion and providing calcitonin protection, as well as methacrylic acid moieties, which act as calcium binders leading to epithelial cell junction opening. Solutions of approximately 0.1 mg/ml of salmon calcitonin were used to load the protein into the gels at pH = 7 and constant ionic strength of 0.1 M. In vitro release studies were performed at pH=7 and 37 deg C, while keeping an ionic strength of 0.1 M. Calcitonin release was achieved. The release behavior was explained in terms of diffusional theories.