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The development of in situ-gelling hydrogels that can enable prolonged protein release is increasingly important due to the emergence of a growing number of protein-based therapeutics. Herein, we describe a high-throughput strategy to fabricate, characterize, and subsequently optimize hydrazone-cross-linked in situ-gelling hydrogels for protein delivery. Hydrogels are fabricated using an automated high-throughput robot to mix a variety of thermoresponsive, nonthermoresponsive, charged, neutral, naturally sourced, and synthetic polymers functionalized with hydrazide or aldehyde groups, generating in situ-gelling hydrogels with well-defined compositions within a 96-well plate. High-throughput characterization strategies are subsequently developed to enable on-plate analysis of hydrogel swelling, mechanics, degradation, transparency, and protein (ovalbumin) release kinetics that yield results consistent with those collected using traditional bulk hydrogel analysis techniques. Dynamic regression and latent variable modeling are then applied to fit performance statistics to the collected data set; subsequently, numerical optimization is used to identify mixtures of precursor polymers that exhibit targeted combinations of minimal burst release, maximum total protein release, minimum release rate, and maximum transparency (the latter of particular relevance for ophthalmic protein delivery applications). Given the rapid throughput of the protocols developed (i.e., 126 hydrogels can be synthesized and screened in quadruplicate within hours), this approach offers particular promise for accelerating the identification of injectable hydrogel compositions relevant for both protein delivery as well as other biomedical applications for which clearly predefined materials properties are required.

Xanthan gum-based microspheres and hydrogels, useful for targeted colorectal release of omega-3 polyunsaturated fatty acids (PUFAs), were successfully prepared and characterized. In particular, the microsphere size, as well as the high hydrogel swelling degree at pH 7.4, and the omega-3 PUFA loading efficiency of both the materials suggested their suitability for colorectal delivery. Moreover, the antioxidant efficiency of the xanthan gum based materials suggests their ability to protect the omega-PUFA cargo. We demonstrated that α-linolenic acid (ALA 18:3ω-3) carried by the materials increased significantly its ability to reduce colorectal cancer cell growth in vitro. On the contrary, docosahexaenoic acid (DHA, 22:6ω-3) enclosed in the hydrogel formulation did not enhance its already high anti-neoplastic potential. The improved anti-neoplastic efficacy of ALA enclosed in both the xanthan gum-based formulations further supports the hypothesis of a potential use of this omega-3 PUFA as a suitable and more sustainable alternative to the fish-derived DHA.

Molecular dynamics (MD) is currently one of the preferred techniques employed to understand hydrogelation processes for its ability to include large amounts of atoms in computational calculations, since substantial amounts of solvent molecules are involved in gel formation. MD studies have helped to rationalize experimental outcomes that in many occasions were not well understood based on experimental observations. Additionally, MD has been used to study changes in gel physical properties triggered by variations in reaction conditions or gelator structures. Changes in many physical properties were understood using MD, including molecular diffusion, hydrogel swelling and volume transitions. All the examples gathered in this review might help the reader to discover the current state of the art in MD studies carried out to study hydrogelation processes as well as the pioneering studies that paved the way to introduce MD in the field of gels., We thank the University of Regensburg, the Deutsche Forschungsgemeinschaft (DFG) (DI 1748/3-1) and Fondecyt Iniciacion (11160707) for financial support. D. D. D. thanks the DFG for the Heisenberg Professorship Award.

Purpose The purpose is to target model drug particles to the posterior region of the suprachoroidal space (SCS) of the eye controlled via pushing by hydrogel swelling. Methods A particle formulation containing 1% hyaluronic acid (HA) with fluorescent polymer particles and a hydrogel formulation containing 4% HA were introduced in a single syringe as two layers without mixing, and injected sequentially into the SCS of the rabbit eye ex vivo and in vivo using a microneedle. Distribution of particles in the eye was determined by microscopy. Results During injection, the particle formulation was pushed toward the middle of the SCS by the viscous hydrogel formulation, but less than 12% of particles reached the posterior SCS. After injection, the particle formulation was pushed further toward the macula and optic nerve in the posterior SCS by hydrogel swelling and spreading. Heating the eye to 37°C, or injecting in vivo decreased viscosity and mechanical strength of the hydrogel, thereby allowing it to swell and flow further in the SCS. A high salt concentration (9% NaCl) in the hydrogel formulation further increased hydrogel swelling due to osmotic flow into the hydrogel. In this way, up to 76% of particles were delivered to the posterior SCS from an injection made near the limbus. Conclusions This study shows that model drug particles can be targeted to the posterior SCS by HA hydrogel swelling and pushing without particle functionalization or administering external driving forces.

Hydrogels are tridimensional elastic hydrophilic cross-linked polymers with the ability to absorb water in a process called swelling. The Flory-Huggins (FH) theory can be applied to model hydrogel swelling with appropriate adjustments. In the literature the FH model parameter is directly estimated from experimental data on swelling. The target of this paper is to evaluate the effect of using parameters estimated from liquid-liquid equilibria of the linear polymer directly in the swelling modeling of the respective cross-linked polymer as these data can be easily found in literature. Three methods that use different equations for the FH parameter and two methods for the mechanical contribution are evaluated. These models were applied to the polymer poly(N-isopropylacrylamide), PNIPA, and compared in three swelling intervals: the volume contraction region; the transition temperature; and the region of volume expansion. The most relevant and important behaviors of each region are shown, analyzed and discussed.

The inline monitoring of ethanol concentrations in liquids is a crucial part of process monitoring in breweries and distilleries. Current methods are based on infrared spectroscopy which are bulky and costly making them non-affordable for small and middle-sized companies. To overcome these problems, we present a small, compact and cost-effective sensing method, based on a nanostructured, plasmonically active sensor substrate. The sensor substrate is coated with a microstructured ethanol-sensitive acrylamide-bisacrylamide hydrogel which induces a change of the hydrogel’s refractive index in conjugation with the hydrogel swelling and shrinking. With such an approach, the ethanol concentration in liquids can be determined in a simple optical transmittance setup. In our study, we demonstrate the capability of the sensor principle for the detection of ethanol concentration ranging from 0 to 30 vol%. Furthermore, we determined the response time of the sensor substrate to be less than 10 seconds, which shows an enormous improvement compared to other hydrogel-based sensing methods. Finally, initial results for real sample measurements are presented.

The potential to develop materials with antibody-like molecular recognition properties has helped sustain interest in protein-imprinted polymers over the past several decades. Unfortunately, despite persistent research, the field of noncovalent protein imprinting has seen limited success in terms of achieving materials with high selectivity and high affinity. In this Perspective, important yet sometimes overlooked aspects of the imprinting and binding processes are reviewed to help understand why there has been limited success. In particular, the imprinting and binding processes are viewed through the scope of free radical polymerization and hydrogel swelling theories to underscore the complexity of the synthesis and behavior of protein-imprinted polymers. Additionally, we review the metrics of success commonly used in protein imprinting literature (i.e., adsorption capacity, imprinting factor, and selectivity factor) and consider the relevance of each to the characterization of an imprinted polymer’s recognition characteristics. Throughout, common shortcomings are highlighted, and experiments that could help verify or disprove the efficacy of noncovalent protein imprinting are discussed.

Various types of hydrogel swelling behaviors can be examined using one of two lattice-based thermodynamic models, a modified double lattice model (MDL) and a Xin model combined with the Flory-Erman theory as a contribution for network elasticity. Depending on the thermoresponsibility of the hydrogel, we investigate the swelling behaviors of lower critical solution temperature (LCST) and upper critical solution temperature (UCST) types. Hourglass, closed-loop, and LCST- and UCST-types are also hypothetically described. In addition, reentrant-type swelling behaviors are analyzed for the given hydrogel systems. The swelling equilibriums of the gel networks are calculated using predetermined molecular interaction parameters obtained from phase equilibrium of the corresponding linear polymer systems. The calculated results for the various types of swelling behaviors verify the applicability of the lattice-based thermodynamic models for swelling equilibrium of the given hydrogel systems.

Permeation through polymeric membranes can be controlled by surface coating of a polyethylene terephthalate (PET) membrane with poly(N-isopropylacrylamide) (PNIPAAm) and inserting pores of defined geometry. When the temperature of the system rises above the volume phase transition temperature, the pores open, which allows permeation of formerly blocked particles. The exact control of the temperature allows defined change of the pore size and therefore enables separation abilities. Free swelling experiments are conducted to obtain the swelling behaviour of PNIPAAm. Then, a temperature expansion model is derived in order to simulate this behaviour with the finite element tool ABAQUS. The gained results are in excellent agreement with the observed shape change. Membranes with permeation control of particles can be used for biomedical application in microfluidics to analyse the size distribution of cells or in chemical information processing as a transistor-like component for an information-bearing chemical species. The possibility to simulate the behaviour of such permeation systems allows computer aided design and prediction of permeation abilities in these areas.

The introduction of the work Makromolekule by Herman Staudinger in 1919 brings back an understanding of the very early days of polymer science when characterizing the molecular structure of exact networks was a main goal of research. Here, we present updates to a swollen polymer network hypothesis with a focus on hydrogel physical properties. We discuss the connections between hydrogel structure, swelling behavior, mechanical properties, and transport properties, including the most substantial developments since the original Flory-Rehner model (1944) of swollen polymer networks. In addition to analyzing well-established and recent contributions to the swollen polymer network hypothesis, we introduce novel amendments that combine the insights of existing models. We suggest that coordinating rubberlike elasticity theory, equilibrium swelling theory, and mesh size theory will help to develop a universal predictive model for swelling, stiffness, and solute diffusivities in a diverse array of hydrogel formulations.

An impregnation of soft contact lenses with salicylic acid in supercritical CO 2 was enhanced by addition of water. The supercritical CO 2 impregnations including water were conducted at 40 °C and 11 MPa with 0.34–2.18 g L −1 of water amount. The contact lenses impregnated in supercritical CO 2 including water result in the high loading-amount of salicylic acid compared with those without water. The higher amount of water in supercritical CO 2 impregnation gives the slower release of salicylic acid from the lenses. The impregnation efficiency of the contact lenses with salicylic acid in supercritical CO 2 including water was evaluated from the loading-amount in the lenses and the concentration in the supercritical CO 2 phase. The efficiencies of supercritical CO 2 impregnation including water are higher than aqueous solution impregnation. The impregnation efficiency of the lenses increases with the water amount in the supercritical CO 2 impregnation processes. The amount of salicylic acid loaded in the lenses also increases with the amount of water dissolved in supercritical CO 2 . A release model using kinetic constant and exponent parameter was applied for modeling the release profile of salicylic acid from the contact lenses. The release modeling suggested that the release from the contact lenses resulted from the superimposition of Fickian controlled and hydrogel swelling controlled releases.

The article are outlined the medicinal use of polymer materials and characteristics and described its preparation method and application for controlled drug release from polymer, polymer drugs, pharmaceutical formulations and packaging polymer materials three aspects. Meanwhile elaborates a novel well dispersed MWCNTs PMAA/MWCNTs nanohybrid hydrogels. The introduction of MWCNTs significantly improved pH-responsive hydrogels and mechanical strength, and which depending on the composition ratio of MWCNTs, particle size and concentration of crosslinker. Study found that hybrid hydrogel swelling rate significantly faster than the pure PMAA hydrogel swelling behavior and this is explained. Compressive stress - strain was found, MWCNTs load transfer heterozygous for improving mechanical properties of the hydrogel network compression plays an important role. MTT cell compatibility evaluation proves that this astute hydrogel biomedical research in particular has potential application value.

This review highlights recent developments in the field of stimuli-responsive hydrogels, focusing primarily on thin films, with a thickness range between 100 nm to 10 μm. The theory and dynamics of hydrogel swelling is reviewed, followed by specific applications. Gels are classified based on the active stimulus—mechanical, chemical, pH, heat, and light—and fabrication methods, design constraints, and novel stimuli-responses are discussed. Often, these materials display large physiochemical reactions to a relatively small stimulus. Noteworthy materials larger than 10 μm, but with response times on the order of seconds to minutes are also discussed. Hydrogels have the potential to advance the fields of medicine and polymer science as useful substrates for “smart” devices. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1084–1099

Biodegradable polymeric microneedles were developed as a method for achieving sustained transdermal drug release. These microneedles have potential as a patient-friendly substitute for conventional sustained release methods. However, they have limitations related to the difficulty of achieving separation of the needles into the skin. We demonstrated that microneedle separation into the skin was mediated by hydrogel swelling in response to contact with body fluid after the needles were inserted into the skin. The hydrogel microparticles were synthesized by an emulsification method using poly-N-isopropylacrylamide (PNIPAAm). The microneedles were fabricated by micromolding poly-lactic-co-glycolic acid (PLGA) after filling the cavities of the mold with the hydrogel microparticles. The failure of microneedle tips caused by hydrogel swelling was studied in regard to contact with water, insertion of microneedles into porcine cadaver skin in vitro, stress-strain behavior, and insertion into the back skin of a hairless mouse in vivo. The drug delivery property of the hydrogel particles was investigated qualitatively by inserting polymer microneedles into porcine cadaver skin in vitro, and the sustained release property of PLGA microneedles containing hydrogel microparticles was studied quantitatively using the Franz cell model. The hydrogel particles absorbed water quickly, resulting in the cracking of the microneedles due to the difference in volume expansion between the needle matrix polymer and the hydrogel particles. The swollen particles caused the microneedles to totally breakdown, leaving the microneedle tips in the porcine cadaver skin in vitro and in the hairless mouse skin in vivo. Model drugs encapsulated in biodegradable polymer microneedles and hydrogel microparticles were successfully delivered by releasing microneedles into the skin.

In this research, an antibiotic was loaded in the composites of polyethylene glycol (PEG), acrylamide (AAm) and acrylic acid (AAc) hydrogels matrices and their drug deliveries were tested. Effect of some parameters on the drug delivery was checked by UV-spectrophotometer. Temperature enhancement considerably increased hydrogel swelling and the drug release in the AAc and AAm. A dynamic model based on the Maxwell–Stefan equation was developed to model the drug delivery of hydrogels. COMSOL software was also applied to simulate buffer diffusion inside the hydrogels.

The objective of presented work is to simulate the response of 2D hydrogel when subjected to the varying pH of buffer solution and initial fixed-charge concentration inside the hydrogel. The novelty of the work is that this is the first attempt to perform the 2D simulation of pH-responsive hydrogel by novel strong-form meshless method, such as random differential quadrature (RDQ) method. The analytical equations, derived for the hydrogel deformation in the x and y directions, are numerically verified by the square shaped hydrogel disc. The jumps in the distributions of ionic concentrations and electrical potential, across the interface between solution and hydrogel, are effectively captured by the RDQ method. A novel approach is proposed to correctly impose natural boundary conditions for non-uniform boundary. The effects of solution pH and initial fixed-charge concentration on the hydrogel swelling are also successfully investigated.

Polyacrylamide (PAAm) hydrogels are commonly employed to ensure soil hydration in horticulture, but studies have shown that they have a minimal effect on crop life and quality. The reasons for this poor performance are not understood since the commercial hydrogels have not been adequately characterized. PAAm hydrogels were synthesized and their properties were measured along with those of commercial hydrogels. Hydrogel swelling, density, and SEM analyses showed that the commercial hydrogels were most likely a derivative of PAAm with ionic groups and they were able to retain moisture for only a few hours.

The purpose of this study was to formulate a superporous hydrogel (SPH) containing carvedilol self-nanoemulsifying drug delivery system. Effects of formulation parameters (amount of SPH and 0.1 N HCl used during drug loading) were studied in 3(2) factorial design. Response surface plots showed significant effect of the parameters on hydrogel swelling, carvedilol content, and carvedilol in vitro release. Regression equations were generated to calculate the desirable responses.

The preliminary results of gel swelling experiments are reported, and then compared to predictions made by a recently-developed finite element model (FEM). This model utilises energy transport between different energy domains, and is being used to simulate gel swelling dynamics. Initial experiments have revealed the model does capture the general behaviour of polymer hydrogel swelling dynamics and further improvements are necessary for better accuracy.

Hydrogels, polymers and various other composite materials may be used in sensing applications in which the swelling or de-swelling of the material in response to some analyte is converted via a transducer to a measurable signal. In this paper, we analyze models used to predict the swelling behavior of hydrogels that may be used in applications related to hydration monitoring in humans. Preliminary experimental data related to osmolality changes in fluids is presented to compare to the theoretical models. Overall, good experimental agreement with the models is achieved.

Corrosion on steel and copper pipes in industry can trigger pollution and weakness due to undesired chemical and biochemical reactions. Too much or too little inhibitor can decrease its efficiency, even causing waste and pollution. In this contribution, an innovative delivery device driven by hydrogel swelling, mainly consisting of a semi-permeable membrane, a hydrogel-swelling force drive and a release orifice, was developed to control the release of inhibitor in a water system at a constant rate, leading the amount of inhibitor to maintain a proper concentration. The effects of hydrogel mass and orifice dimension on release property were studied for controlling release rate. Moreover, a weight loss experiment on carbon steels was carried out to show the incredible anti-corrosion function of the system.

A facile method for the characterization of hydrogel swelling is described which is based on the determination of changes in the liquid phase concentration of an excluded tracer as gel swells in a constant volume system. The utility of this approach is demonstrated with two responsive hydrogel preparations, one where swelling is influenced by system pH, the other by changes in specific solute concentration.

Although studies of charged hydrogel swelling focus on the swelling transition, hydrogels display pre‐transition swelling which may affect their performance in applications such as sensors. In this paper we investigate the effect of system parameters on the pre‐transition swelling of charged poly methacrylic acid (PMAA) hydrogels. We find that the pre‐transition swelling can be quite significant in magnitude (in our case ∼40% of the maximal swelling). Increasing the sub‐chain molecular weight increases swelling in the pre‐transition region only in the case where no salt is added; Contrary to expectation, in moderate ionic strength solutions the degree of swelling of longer chains is lower than that of shorter sub‐chains. Also contrary to expectation, in the case of longer sub‐chains the addition of salt decreases the gel volume in the pre‐transition region, thereby indicating that in this system a significant number of charges are dissociated. These trends can be understood by accounting for the ...

The ability of hydrogels to respond to relatively small changes in stimuli with relatively large changes in volume allows a wide variety of applications. This chapter addresses hydrogels with regard to the chemical identity of hydrophilic polymers and copolymers, polymer synthesis, the degree of crosslinking and hydrogel porosity, and bulk geometry of hydrogels in the form of matrix, membrane and erodible systems. The relationships between these features and hydrogel swelling behavior upon stimulation are also described. Finally, various exploitations of hydrogel swelling behavior in developing highly sensitive, real-time biosensors are discussed.

Hydrogels have found wide application in biosensors due to their versatile nature. This family of materials is applied in biosensing either to increase the loading capacity compared to two-dimensional surfaces, or to support biospecific hydrogel swelling occurring subsequent to specific recognition of an analyte. This review focuses on various principles underpinning the design of biospecific hydrogels acting through various molecular mechanisms in transducing the recognition event of label-free analytes. Towards this end, we describe several promising hydrogel systems that when combined with the appropriate readout platform and quantitative approach could lead to future real-life applications. This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A method for hydrogel swelling kinetics measurement has been demonstrated by working with impedance analyzing technique.

In this paper a sensor is presented for the detection of carbon dioxide gas inside the stomach in order to diagnose gastrointestinal ischemia. The operational principle of the sensor is measuring the CO/sub 2/ induced pressure generation of a confined pH-sensitive hydrogel by means of a micro pressure sensor. The sensor is capable of measuring CO/sub 2/ with a response time between 2 and 4 minutes and a maximum pressure of 0.29/spl times/10/sup 5/ Pa at 20 kPa CO/sub 2/. The sensor is able to resist up to 1 M HCl acid as can be present inside the stomach. The results are very promising for real application and clinical trials are planned.

Hydrogels containing benzo-18-crown-6 were used to modify microcantilevers for measurements of the concentration of Pb2+ in aqueous solutions. These microcantilevers undergo bending deflection upon exposure to solutions containing various Pb2+ concentrations as the result of a swelling of the hydrogels. It was found that a concentration of 10(-6) M Pb2+ can be detected using this technology. Other cations, such as Na+, have no effect on the deflection of this cantilever. The cation K+, which also complexes with benzo-18-crown-6, could interfere with Pb2+ detection, but only at high concentrations (> 10(-4) M).

An oligonucleotide–polymer hybrid hydrogel displaying swelling response in a logical AND and OR fashion depending on specific stimuli by probe oligonucleotides was prepared. The hydrogel acts as a transducer of the specific recognition of DNA sequences into micro- and macroscale mechanics. Input oligonucleotide probes induce hydrogel swelling ratio at two signal levels.