TY - JOUR TI - Design and characterization of salicylic acid-based hydrogels for protein delivery applications DO - https://doi.org/doi:10.7282/T3VX0JKD PY - 2016 AB - Combination drug delivery has received much attention in the pharmaceutical industry to meet the need for increased efficacy and improved patient compliance. Hydrogels are cross-linked networks of hydrophilic polymers that resembles natural tissue and thus successfully developed for drug delivery applications. In three separate chapters, this dissertation describes novel salicylic acid-based hydrogel systems that concurrently deliver salicylic acid as well as the encapsulated protein. The hydrogels systems described herein are formed via physically and chemically cross-linking techniques. First, salicylic acid-based poly(anhydride-esters) were physically cross-linked with poly(N-isopropylacrylamide-co-acrylic acid) via a solvent-casting technique to form injectable hydrogel systems. The physical interactions between these polymer systems were characterized by Fourier transform infrared spectroscopy. Bovine serum albumin, a representative protein, was successfully incorporated into the hydrogel systems. The release profiles of both salicylic acid and bovine serum albumin were ascertained. Second, salicylic acid-based poly(anhydride-esters) were physically cross-linked with poly(acrylic acid) to develop pH-sensitive hydrogels for oral protein delivery. These systems were characterized using spectroscopic techniques such as Fourier transform infrared spectroscopy. Insulin was incorporated into these systems, release of both insulin and salicylic acid was determined to be pH-dependent. The physical and chemical stability of insulin was characterized following release from the hydrogel system. In addition, these systems displayed mucoadhesive behavior which may further enable insulin bioavailability. The results suggest that these systems may be useful for oral administration of insulin and salicylic acid. Third, salicylic acid was chemically incorporated into hydrogel systems via attachment of salicylic acid to an itaconate moiety followed by cross-linking using acrylic acid and poly(ethylene glycol)-diacrylate via UV. The structure, swelling behavior, pore structure, salicylic acid release, rheological, and mucoadhesion behavior of these hydrogels were studied. These hydrogels systems showed pH-responsive behavior: collapsing at acidic pH levels and leading to slower salicylic acid release, and swelling at higher pH conditions leading to salicylic acid release within 24 hours. Pore structure analysis showed a promising pore size for physically encapsulating of proteins. In conclusion, these results suggested that these systems can potentially be used in combination delivery of proteins and salicylic acid. KW - Chemistry and Chemical Biology KW - Colloids KW - Drug delivery systems LA - eng ER -