Enhanced Mucoadhesive Capacity of Novel Co-polymers for Oral Protein Delivery

Graft co-polymer networks have shown promise as devices for oral delivery of proteins. By increasing adhesion of these networks at the delivery site of the upper small intestine by utilizing small covalent chemical linkages caused by the addition of an aldehyde functional group we can make them more viable. These aldehydes bind covalently by way of a condensation reaction with the amines of the amino acids found in the glycoprotein network of the mucus layer of the small intestine to form imines. To investigate the effectiveness of this linkage the co-polymers are prepared in three different percentages of poly(ethylene glycol) (PEG) and aldehyde-modified PEG, and characterized through swelling, release and adhesion testing. The percentages of aldehyde-modified PEG used are 0.06, 0.6 and 3.3%. The swelling results indicate that the formulations with the aldehyde-modified PEG maintained the same pH sensitivity and transition around a pH of 5.8 as those formulations without the aldehyde moiety. Release results indicate that the release of insulin of the most promising 3.3% aldehyde formulation was successful with a release of about 80% after 3 h, which compares favorably with the similar release of the controls done in previous work. Adhesion testing was carried out through the use of a mechanical testing apparatus. Data have been gathered and plotted to give a detachment force (N) versus displacement (m) curve, of which the work of adhesion (mu J) was found by taking the area underneath the curve. Adhesion results indicate an increase to the already present adhesion of the co-polymers due to increased percentages of the aldehyde-modified PEG tethers where the 3.3% formulation showed an increase of 10-30 mu J over both control formulations. (C) Koninklijke Brill NV, Leiden, 2011