Methods and Materials Aldehyde Synthesis: The aldehyde was synthesized by oxidation of PEG dissolved in dichloromethane with sieves and NMO. TPAP was added as the catalyst then the reaction was followed by thin layer chromotography. The reaction was complete when the solution went from green to black and then diluted with more dicholoromethane and washed with sodium sulfite solution and brine and finally with saturated copper (II) sulfate. The organic layer was dried, filtered, and worked up in the usual way to give the pure aldehyde Hydrogel (P(MAA-EG) )Synthesis: Swelling and Adhesion Studies: The hydrogel was dried in a vacuum oven and the dry weight recorded. It is soaked for either five minutes at a time in each, or one in each for 48 hours, in ten buffers with a different pH ranging from 3.2 to 7.6. Using the swollen weight, swelling ratio, Q, was calculated and plotted against pH. For the adhesion study, a polymer disc was placed on the upper clamp of the Instron. Porcine mucin solution was placed on the bottom dish in a buffer solution. These two clamps were brought into contact and then gradually pulled apart until fully separated. Methods and Materials Aldehyde Synthesis: The aldehyde was synthesized by oxidation of PEG dissolved in dichloromethane with sieves and NMO. TPAP was added as the catalyst then the reaction was followed by thin layer chromotography. The reaction was complete when the solution went from green to black and then diluted with more dicholoromethane and washed with sodium sulfite solution and brine and finally with saturated copper (II) sulfate. The organic layer was dried, filtered, and worked up in the usual way to give the pure aldehyde Hydrogel (P(MAA-EG) )Synthesis: Swelling and Adhesion Studies: The hydrogel was dried in a vacuum oven and the dry weight recorded. It is soaked for either five minutes at a time in each, or one in each for 48 hours, in ten buffers with a different pH ranging from 3.2 to 7.6. Using the swollen weight, swelling ratio, Q, was calculated and plotted against pH. For the adhesion study, a polymer disc was placed on the upper clamp of the Instron. Porcine mucin solution was placed on the bottom dish in a buffer solution. These two clamps were brought into contact and then gradually pulled apart until fully separated. Background Information and Motivation for Research: o Diabetes is a disease that affects millions of people worldwide, many requiring insulin delivery to the blood stream o Many proteins, such as insulin, can only be delivered via injections due to their degradation in the acidic environment of the stomach o The pain and possible side effects of daily injections lead to patient noncompliance o Oral delivery methods are being researched, but the bioavailability of some of these methods is limited by residence time in the intestines 1 A Possible Solution o Oral delivery methods are preferable over the injections in order to mimic the natural pathway of insulin and increase patient compliance 2 o Using a complexation hydrogel, poly(methacrylic acid-g-ethylene glycol), P(MAA-g-EG), enclosed insulin would be released in the neutral environment of the intensines after been collapsed in the low pH of the stomach 2,3 o P(MAA-g-EG) has been shown to be adhesive to the mucous on the intestinal walls More research is needed on increasing the residence time Hypothesis Utilize the Schiff’s Base Reaction with the glycoproteins present in the mucus layer by incorporating an aldehyde moiety into the hydrogel structure Step 1 Mix components in 50:50 monomer:solvent ratio Step 2 Sonicate solution Step 3 Purge with N 2 to remove O 2 Step 4 Pour between glass slides Step 5 UV polymerize Step 6 Wash film for seven days Results Swelling Study will be two graphs here. One will be a plain dynamic swelling study for P(MAA) and the other will have a comparison of P(MAA-g- EG) to the 5% aldehyde hydrogel Instron Work will be a bar graph comparing P(MAA) with P(MAA-g-EG) with 5% aldehyde tethers Discussion and Conclusion *obviously a projection of results… The swelling studies show that the addition of 5% aldehyde tethers to the original P(MAA-g-EG) does not affect the pH sensitivity or the swelling volume. The Schiff’s reaction appears successful in increasing the mucoadhesion with the increase of aldehyde tethers. In conclusion, there is no negative effect from the addition of the aldehyde tethers to the original benefits of using the hydrogel for oral delivery of insulin, with the added benefit of increased residence time due to the advanced mucoadhesion. Future work is suggested in testing the mucoadhesion using AFM to detect the attraction of the hydrogel to mucous without initial contact. References 1.Tuesca, A., Nakamura, K., Morishita, M., Joseph, J., Peppas, N., Lowman, L. Complexation Hydrogels for Oral Insulin Delivery: Effects of Polymer Dosing on In Vivo Efficacy. J. Pharm Sci. 2008, 97: Carino, G.P., Mathiowitz, E. Oral Insulin Delivery. Adv Drug Deliv Rev. 1999, 35: Peppas, N.A. Devices Based on Intelligent Biopolymers for Oral Protein Delivery. I. J. Pharm. 2004, 277:

Background Information and Motivation for Research: o Diabetes is a disease that affects millions of people worldwide, many requiring insulin delivery to the blood stream o Many proteins, such as insulin, can only be delivered via injections due to their degradation in the acidic environment of the stomach o The pain and possible side effects of daily injections lead to patient noncompliance o Oral delivery methods are being researched, but the bioavailability of some of these methods is limited by residence time in the intestines 1

A Possible Solution o Oral delivery methods are preferable over the injections in order to mimic the natural pathway of insulin and increase patient compliance 2 o Using a complexation hydrogel, poly(methacrylic acid-g-ethylene glycol), P(MAA-g-EG), enclosed insulin would be released in the neutral environment of the intensines after been collapsed in the low pH of the stomach 2,3 o P(MAA-g-EG) has been shown to be adhesive to the mucous on the intestinal walls More research is needed on increasing the residence time

Methods and Materials Aldehyde Synthesis: The aldehyde was synthesized by oxidation of PEG dissolved in dichloromethane with sieves and NMO. TPAP was added as the catalyst then the reaction was followed by thin layer chromotography. The reaction was complete when the solution went from green to black and then diluted with more dicholoromethane and washed with sodium sulfite solution and brine and finally with saturated copper (II) sulfate. The organic layer was dried, filtered, and worked up in the usual way to give the pure aldehyde Hydrogel (P(MAA-EG) )Synthesis: Swelling and Adhesion Studies: The hydrogel was dried in a vacuum oven and the dry weight recorded. It is soaked for either five minutes at a time in each, or one in each for 48 hours, in ten buffers with a different pH ranging from 3.2 to 7.6. Using the swollen weight, swelling ratio, Q, was calculated and plotted against pH. For the adhesion study, a polymer disc was placed on the upper clamp of the Instron. Porcine mucin solution was placed on the bottom dish in a buffer solution. These two clamps were brought into contact and then gradually pulled apart until fully separated. Step 1 Mix components in 50:50 monomer:solvent ratio Step 2 Sonicate solution Step 3 Purge with N 2 to remove O 2 Step 4 Pour between glass slides Step 5 UV polymerize Step 6 Wash film for seven days

Results Swelling Study will be two graphs here. One will be a plain dynamic swelling study for P(MAA) and the other will have a comparison of P(MAA-g- EG) to the 5% aldehyde hydrogel Instron Work will be a bar graph comparing P(MAA) with P(MAA-g-EG) with 5% aldehyde tethers

Discussion and Conclusion *obviously a projection of results… The swelling studies show that the addition of 5% aldehyde tethers to the original P(MAA-g- EG) does not affect the pH sensitivity or the swelling volume. The Schiff’s reaction appears successful in increasing the mucoadhesion with the increase of aldehyde tethers. In conclusion, there is no negative effect from the addition of the aldehyde tethers to the original benefits of using the hydrogel for oral delivery of insulin, with the added benefit of increased residence time due to the advanced mucoadhesion. Future work is suggested in testing the mucoadhesion using AFM to detect the attraction of the hydrogel to mucous without initial contact.