Molecular Design and in Vitro Studies of Novel pH-Sensitive Hydrogels for the Oral Delivery of Calcitonin

pH-sensitive hydrogels are suitable candidates for oral drug delivery of peptides due to their ability to respond to their environment. We have developed new hydrogels composed of poly(methacrylic acid) (PMAA) grafted with poly(ethylene glycol) (PEG) (P(MAA-g-EG)) which can be used as drug delivery carriers for salmon calcitonin. P(MAA-g-EG) hydrogels were prepared by free radical solution polymerization. The monomer mixture was diluted using a 50% w/w solution of ethanol and water. The percentage of monomer in solution was varied from 84% to 45% v/v. Swelling studies were conducted to investigate the effects of solvent content used during polymer preparation in the swelling behavior. The effects of dilution on the swelling behavior were not observed until the monomer mixture was diluted to approximately 50%. Salmon calcitonin was successfully incorporated and released in vitro from the system. 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. The loading efficiency was affected by the amount of solvent used during hydrogel preparation. In vitro release studies were performed at pH ) 7 and 37 °C, while keeping an ionic strength of 0.1 M. The release behavior was found to be not very much affected by the amount of diluent used during polymer preparation. The transport mechanism was found to be relaxation controlled for all cases, and the diffusion coefficient was estimated using a heuristic Fickian/relaxational model.