Molecular design of environmentally sensitive complexation hydrogels for oral protein delivery
Abstract
Novel pH-sensitive complexation hydrogels containing pendent glucose (P(MAA-co-MEG)) or grafted PEG chains (P(MAA-g-EG)) were synthesized by photopolymerization. These hydrogels showed excellent properties for oral protein delivery carriers such as pH-responsive swelling behavior and protective ability for protein. Both classes of the hydrogels exhibited sharp transitions between the swollen and the collapsed states at pH 5. Their equilibrium swelling ratio increased at pH values above 5, but decreased at pH values below 5. The swelling behavior was controlled more by polymer relaxation (Case II) than by penetrant diffusion at pH 7.0. The effect of complexation on the molecular network structure was investigated using ATR-FTIR spectroscopy. Both P(MAA-co-MEG) and P(MAA-g-EG) networks could form hydrogen bonds at low pH (below 5) by protonation of the carboxylic acid groups of the PMAA, while electrostatic interaction prevailed at high pH (above 5) due to the ionization of the carboxylic acid groups of the PMAA. At low pH, the presence of the grafted PEG chains contributed to the formation of more hydrogen bonding. However, the presence of pendent glucose groups disrupted the hydrogen bonding between the carboxylic acid groups of the PMAA. The feasibility of these hydrogels as oral protein delivery carriers was also evaluated. The pH-responsive release behavior of insulin was observed from both P(MAA-co-MEG) and P(MAA-g-EG) hydrogels. In acidic media (pH 2.2), insulin release from the hydrogels was very slow. However, as the pH of the medium was changed to 6.5, a rapid release of insulin occurred. After treatment with a simulated gastric solution, the biological activity of insulin that was inside both classes of hydrogels was retained. In P(MAA-co-MEG) hydrogels, insulin biological activity decreased when the pendent glucose content increased. In P(MAA-g-EG) hydrogels, when the grafted PEG molecular weight increased, insulin biological activity decreased. Finally, hydrogels of P(MAA-co-MEG) prepared with an initial ratio of 1:4 MEG:MAA and P(MAA-g-EG) containing PEG chain of 200 molecular weight showed the greatest change in insulin release rate from acidic to basic pH solutions and the greatest protective effect for insulin in the simulated GI tract condition.
Degree
Ph.D.
Advisors
Peppas, Purdue University.
Subject Area
Chemical engineering|Biomedical research
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