Biomaterials25(2004)4345–4353 Controllingthecollapse/swellingtransitioninchargedhydrogels JamieOstroha,MonaPong,AnthonyLowman,N.Dan* Department of Chemical Engineering, Drexel University, Philadelphia, PA, USA Received15August2003;accepted12November2003 Abstract Inthispaper,weinvestigatesystematicallytheparameterscontrollingtheswellingtransitionofchargedhydrogels.Combining theoreticalanalysisandexperimentalinvestigationswecharacterizethetransitionpHandthewidthofthetransitionasafunctionof thehydrogelcrosslinkdensity(i.e.subchainmolecularweight)andthesolutionsaltconcentration.Wealsoinvestigatetheeffectof pendantpolyethyleneglycol(PEG)sidechainsontheswellingtransition.Quitesurprisingly,wefindthat(1)thedegreeofswelling varies non-monotonically withthesolutionsaltconcentration,firstincreasingandthendecreasingwithsalinity,(2)eveninthelimit ofhighsaltconcentrations,whereelectrostaticsareexpectedtoplayaminorrole,wefindthatthedegreeofswellingisquitesensitive tothesuspensionpH,namely,tothegeldegreeofcharging,(3)inthelimitoflongsubchainsthetransitionpHdependsonlyonthe chemistryofthegelcharges,andthetransitionisquitesharp,(4)thetransitionpHshiftswithdecreasingsubchainlengthand/or with decreasing salt concentration, and the width of the transition increases and (5) the overall degree of swelling increases significantly upon the incorporation of pendent PEG chains, while the transition pH remains unaffected and the width of the transitionnarrowssignificantly. r 2003ElsevierLtd.Allrightsreserved. Keywords: Drugrelease;Hydrogel;Swelling;PolymethacrylicacidP(MAA) 1. Introduction Hydrogelsarethree-dimensional,water-swellablenet- worksconnectedbychemicalorphysicalcrosslinks.One of the more interesting, and technology promising, featuresofhydrogelsistheirabilitytotransitionfroma collapsed state to a highly swollen one, in aqueous solutions,inresponsetoenvironmentalchanges [1–5]. Generally,hydrogelscanbedividedintotwoclasses; neutralandcharged.Neutralhydrogelsarecomposedof polymerchainsthatarewater-soluble(e.g.polyethylene glycol (PEG), poly-N-isopropylacrylamide). Swelling is arrestedinthesegelswhentheosmoticpressureofthe solventisbalancedwiththesubchainstretchingenergy. Theircollapsedtoswollentransitiongenerallyoccursas a result of changes in the temperature, which controls thepolymersolubility(see,forexample, [6–10]). Charged, or polyelectrolyte hydrogels are composed of polymer chains containing charged groups. Unlike theunchargedhydrogels,thedominantdrivingforcefor swelling in these systems is the inherent electrostatic repulsion between gel charges (see Fig.1):Asaresult, swelling of polyelectrolyte hydrogels can be induced throughsuchstimuliaschangesinpHandsalinity(see, forexample, [11–25]). The ability of charged hydrogels to transition, in responsetoanenvironmentaltrigger,fromacollapsed toswollenconfigurationorviceversamaybeutilizedfor varioustechnologicalapplications.Forexample,hydro- gelshavebeenwidelyexaminedasdrugdeliveryagents (see, for example, [26–29]) where the swelling trigger leadstothereleaseofpharmaceuticalsentrappedinthe collapsed gel. Thus, successful utilization of charged hydrogels requires understanding, and control, of the swellingtransitionmechanism. The relationship between the system pH and the swellingtransitionofchargedhydrogelshasbeenwidely examined (see, for example, [12–23]). They find that swelling in acidic or basic hydrogels (i.e., hydrogels carrying acidic or basic groups) is indeed triggered by pH changes [12–23].Asmaybeexpected,themaximal degree of swelling was found to increase with the subchain length (i.e., the length of chains between ARTICLE IN PRESS *Correspondingauthor. E-mail address: dan@coe.drexel.edu(N.Dan). 0142-9612/$-seefrontmatter r 2003ElsevierLtd.Allrightsreserved. doi:10.1016/j.biomaterials.2003.11.019