pH-Responsive Hydrogel with Controlled Swelling and Degradation Rate Marianela Trujillo-Lemon * , Christopher N. Bowman ** and Jeffrey W. Stansbury * * University of Colorado Health Sciences Center, Aurora 80045, CO, USA ** University of Colorado, Boulder, CO 80309, USA ABSTRACT A range of hydrogels were prepared by solution polymerization of methacrylic acid, poly(ethyleneglycol) methyl ether methacrylate (M.W. 475 g/mol) and poly(ethyleneglycol) dimethacrylate (as the cross-linking, M.W. 550 or 875 g/mol) in various proportions. The effects of methacrylic acid/ poly(ethyleneglycol) methyl ether methacylate concentration ratios as well as cross-linking concentration in the degree of swelling as a function of the media pH were studied. Reversibility of the swelling process was confirmed. Degradation in the system described previously was introduced using a hydrolytically labile diacrylate cross-linker (A-PLA-PEG-PLA-A) instead of the poly(ethyleneglyco) dimethacrylates. The degrees of swelling and degradation rates at different pH were studied. Hydrolytically degradable polymers that respond to pH stimuli to activate the swelling and decomposition process were developed. Multiple interrelated control parameters dictated by the synthetic recipe were studied and are available to separately control swelling and degradation rates of these novel polymers. Keywords: hydrogel, pH-responsive, swelling, degradation 1 INTRODUCTION “Smart” hydrogels as drug delivery vehicles, which once introduced in the body, controllably release the right amount of drug, protein or peptide in response to internal or external stimuli, e.g., temperature [1], pH [2],[3] glucose [4], electric field [5], ultrasound [6], etc have received considerable attention in the last past years. However, the development of polymeric systems that couple stimuli response with degradability in hydrogels for controlled release is much more limited [7], [8]. Nevertheless, a biodegradable hydrogel system can present very important advantages since it contributes an additional degree of control over the release of drug or other bioactive component while on the other hand, once implanted in the body, it can be cleared readily after depletion of the agent. For a novel drug delivery application, a polymeric material was required that could serve as a stable matrix for prolonged periods of aqueous media storage without undergoing degradation or allowing release. Following introduction into the body controlled swelling, degradation and release was desired. Since modest alterations in pH can be temporarily tolerated and moderated in the body, a pH- responsive, degradable hydrogel material was developed. Hydrogels capable of response to a pH-based stimulus are typically reliant on polymeric structures containing ionizable groups of a week acid (carboxylic or sulfonic acid) or a week base (amino group). Amine substitution results in swelling in acidic pH solutions due to formation of an ammonium polyelectrolyte. Conversely, carboxylic acid substituents form ionized salts at neutral or basic pH resulting in increased network swelling. So, it is possible to produce stable complexes under acidic or basic conditions depending of the target applications. Typically, polymer networks containing poly (methacrylic acid) or poly (acrylic acid) can form hydrogen-bonding complexes that are stable under acidic conditions [9]. More stable complexes tend to be formed with the more rigid methacrylate acid backbone structures. Klier and Peppas first studied copolymers [10] formed from (methacrylic acid) and poly(ethylene glycol) monomethacrylate, which is the basic approach selected in our investigation. Intra- and inter- molecular complexes in this system are formed due to the cumulative strong hydrogen bonding interactions between the carboxylic acid groups along the polymer backbone and the poly(ethylene glycol) (PEG) ether oxygen located in the side chains. Under acid conditions, the P(MAA-g-PEGMEMA) hydrogels assume a collapsed , hydrophobic structure with low degrees of swelling and permeability. In the current study, cross- linking in the pH-responsive system is introduced using the hydrolytically labile A-PLA-b-PEG-b- PLA-A originally described by Sawhney et al. [11]. In the present work, we describe the synthesis of pH-responsive hydrogel with potential use for delivery of drugs or other biomedical applications. The goal is to better understand the parameters that control the interrelated swelling and degradation behavior of the hydrogels. To accomplish this, pH-dependent swelling of non-degradable model systems is studied along with investigations of the swelling and mass loss profiles of the fully degradable hydrogels. 2 MATERIALS AND METHODS 2.1 Synthesis of non-degradable hydrogels Hydrogels were synthesized by free radical copolymerization of poly(ethyleneglycol)methyl ether methacrylate 475(PEGMEMA-475) with methacrylic acid NSTI-Nanotech 2005, www.nsti.org, ISBN 0-9767985-0-6 Vol. 1, 2005 148