Ion Concentration of External Solution as a Characteristic of Micro- and Nanogel Ionic Reservoirs Sergey Kazakov,* ,² Marian Kaholek, ‡ Irina Gazaryan, § Boris Krasnikov, § Korki Miller, ² and Kalle Levon ‡ Department of Chemistry and Physical Sciences, Pace UniVersity, 861 Bedford Road, PleasantVille, New York 10570, Polymer Research Institute, Polytechnic UniVersity, Six MetroTech Center, Brooklyn, New York 11201, and Burke Medical Research Institute, 785 Mamaroneck AVenue, White Plains, New York 10605 ReceiVed: February 17, 2006; In Final Form: June 12, 2006 Ion-sensitive hydrogel is regarded as an ionic reservoir, i.e., a system capable of changing the external pH or ionic strength by accumulating or releasing ions. The concept of a hydrogel ionic reservoir was demonstrated for hydrogel particles of three different size ranges: macrogel (1000-6000 μm), microgel (∼20-200 μm), and nanogel (∼0.2 μm). Ion sensitivity of poly(N-isopropylacrylamide-co-1-vinylimidazole) (PNIPA-VI) microgels with imidazolyl (ionizable) groups was confirmed by the pH dependence of their volume, while nanogels were characterized by dynamic light scattering. On the contrary, the volume of poly(N- isopropylacrylamide) (PNIPA) microgels without ionizable groups was pH independent in the whole range of pH from 10 to 2. Four distinct regions of pH-behavior were observed for PNIPA-VI hydrogel micro- and nanoparticles using potentiometric titration of their suspensions. Time-resolved measurements of ion concentrations in the suspension of hydrogel particles revealed a substantial difference in kinetics of pH equilibration for (i) ion-sensitive hydrogels (PNIPA-VI) vs hydrogels without ionizable groups (PNIPA) and (ii) PNIPA-VI hydrogels of different sizes. On the basis of the experimental observations, a two-step mechanism affecting the kinetics of proton uptake into the hydrogel particles with ionizable groups was proposed: (1) fast binding of ions to the immediate surface of each particle and (2) a slower successive diffusion of bound sites into the next inner layer of polymer network. In accord with the mechanism proposed, a quasi-chemical kinetic model of pH relaxation to equilibrium was developed to fit the experimental data for the time course of proton uptake by macro-, micro-, and nanogels into two exponentials with the characteristic times of τ 1 and τ 2 . We believe the same kinetic model will be pertinent to describe phenomenological and molecular mechanisms controlling proton transport in/out bacteria, cells, organelles, drug delivery vehicles, and other natural or artificial multifunctional ionic containers. The approach can be easily extended for the other ions (e.g., Na + ,K + , and Ca 2+ ). Introduction Ion-sensitive hydrogels are of great potential for diverse applications, such as an environmentally responsive element in drug delivery systems, 1,2 compliant actuators or “artificial muscles”, 3-7 and an element supporting bilayer lipid membrane in biosensory devices. 8-10 According to the recognized concept of a gel-like cytoplasm, 11 a cytoplasmic protein-ion-water matrix may operate by the same working principles as an ordinary hydrogel ionic reservoir. Thus, the kinetics of ion exchange within the artificial polymer networks may model some of the living cell functions. The physical dimension of polymer networks containing ionizable groups results from a balance between the electrostatic interactions of charged polymer chains and network elasticity, 12-27 i.e., the ability of ion-responsive hydrogels to swell or shrink reversibly is mainly controlled by the charge on the network, the counterions associated with the network charge, and the difference in concentration of mobile ions inside hydrogel and in the exterior solution. The ion-responsive polymer network is able to store intrinsic chemical energy by accumulating or releasing ions. 26,28 The interior of an ionic hydrogel particle bearing many charged (ionizable) groups that cannot move out of the gel, may be considered as a solution separated from the external solution by a semipermeable membrane. The equilibrium distribution of ions between those hydrogel particles and external solution is determined by a Donnan theory. A vast pool of relatively recent studies [refs 18-26, 29-34, and references therein] has been devoted to the charge controlled behavior of ionic micro- gels in equilibrium. Our particular interest is in the transitional kinetics of approaching the ionic equilibrium in the hydrogel particles’ suspensions, i.e., the time course of external pH changes when a hydrogel with the known concentration of ionizable groups is added to or when an acid or base is injected into the hydrogel suspension. Since the regulation of external pH and/ or ion concentration produces electrochemical and mechanical transformations in the polymeric network, the rates of those responses are important quantitative characteristics of the ionic reservoir, though unknown. Nonetheless, one can assume that the rate and effectiveness of the ionic reservoir in accumulating or releasing ions can be increased by decreasing the size of hydrogel particles. This effect remains to be proven, however. * To whom correspondence should be addressed. Phone: (914) 773- 3774. Fax: (914) 773-3418. E-mail: skazakov@pace.edu. ² Pace University. ‡ Polytechnic University. § Burke Medical Research Institute. 15107 J. Phys. Chem. B 2006, 110, 15107-15116 10.1021/jp061044i CCC: $33.50 © 2006 American Chemical Society Published on Web 07/15/2006