Hydrogel Network Formation Research Articles

Bacteria encapsulation into polyethylene glycol hydrogels using Michael-type addition reactions

AbstractHydrogel materials can be used to integrate bacteria cells into biohybrid systems. Here, we investigate the use of polyethylene glycol-based hydrogels that employ different Michael-type addition crosslinking chemistries, including thiol-acrylate, thiol-vinyl sulfone, and thiol-maleimide click reactions, for covalent hydrogel network formation and bacteria encapsulation. All crosslinking chemistries generated hydrogels that provided stable encapsulation and culture of Bacillus subtilis; however, significant differences in cell viability and cell morphology after encapsulation were identified. Thiol-acrylate hydrogels provided the highest cell viability and favored encapsulation of single cells, while thiol-maleimide hydrogels had the lowest cell viability and favored encapsulation of larger aggregates. These findings demonstrate the impact of crosslinking strategies for encapsulation of microorganisms into hydrogel networks and suggest that thiol-acrylate chemistries are favorable for many applications. Graphical abstract

Inherent Tumor Microenvironment‐Reversing Hydrogels: Potentiating Molecular Therapy Efficacy Against Drug‐Resistant Tumors

AbstractThe tumor microenvironment is a pivotal driver of tumor progression, highlighting the potential of microenvironment reversal as a promising breakthrough in cancer therapy. However, the current tumor microenvironment reversing capacity through targeted drug delivery remains limited, posing a significant challenge in the biomedical field. In this study, a materials science strategy to achieve an inherently efficient reversal of the solid tumor microenvironment while potentiating molecular therapy efficacy against drug‐resistant tumors is proposed. To construct bioactive hydrogel materials, biocompatible and acid‐reversible nanoclays are utilized as building blocks, and peptide polydendrons are designed as supramolecular cross‐linkers. To drive hydrogel network formation, bioactive hydrogels are capable of reversing tumor acidotic microenvironment, integrating superior mechanical properties, injectability, self‐healing capability, and drug‐loading capacity. Through a drug‐resistant cell line in vitro and a tumor‐bearing mouse model in vivo, the hydrogel materials successfully modulate acidic accumulation resulting from tumor metabolic abnormalities and reverse the acidic microenvironment within the tumor tissue. Remarkably, the tumor microenvironment‐reversing hydrogels effectively suppress tumor cell proliferation, migration, and invasion, while significantly amplifying the antitumor drug efficacy. The bioactive hydrogel materials offer an innovative avenue for reversing the tumor microenvironment, displaying promising prospects for clinical translation and applications.

Hydroxyethyl Cellulose-Based Hydrogels as Controlled Release Carriers for Amorphous Solid Dispersion of Bioactive Components of Radix Paeonia Alba.

Radix Paeoniae Alba (RPA) has been used extensively in Chinese traditional medicine to treat gastrointestinal disorders, immune-modulating diseases, cancers, and numerous other conditions. A few of its active components include paeoniflorin, albiflorin, lactiflorin, and catechin. However, their therapeutic effectiveness is compromised by poor pharmacokinetic profiles, low oral bioavailability, short half-lives, and poor aqueous solubility. In this study, hydroxyethyl cellulose-grafted-2-acrylamido-2-methylpropane sulfonic acid (HEC-g-AMPS) hydrogels were successfully prepared for the controlled release of Radix Paeonia Alba-solid dispersion (RPA-SD). A total of 43 compounds were identified in RPA-SD using UHPLC-Q-TOF-MS analysis. The hydrogel network formation was confirmed by FTIR, TGA, DSC, XRD, and SEM. Hydrogels' swelling and drug release were slightly higher at pH 1.2 (43.31% swelling, 81.70% drug release) than at pH 7.4 (27.73% swelling, 72.46% drug release) after 48 h. The gel fraction, drug release time and mechanical strength of the hydrogels increased with increased polymer and monomer concentration. Furthermore, the hydrogels were porous (84.15% porosity) and biodegradable (8.9% weight loss per week). Moreover, the synthesized hydrogels exhibited excellent antimicrobial and antioxidative properties.

Thermo-responsive Diels-Alder stabilized hydrogels for ocular drug delivery of a corticosteroid and an anti-VEGF fab fragment

In the present study, a novel in situ forming thermosensitive hydrogel system was investigated as a versatile drug delivery system for ocular therapy. For this purpose, two thermosensitive ABA triblock copolymers bearing either furan or maleimide moieties were synthesized, named respectively poly(NIPAM-co-HEA/Furan)-PEG6K-P(NIPAM-co-HEA/Furan) (PNF) and poly(NIPAM-co-HEA/Maleimide)-PEG6K-P(NIPAM-co-HEA/−Maleimide) (PNM). Hydrogels were obtained upon mixing aqueous PNF and PNM solutions followed by incubation at 37 °C. The hydrogel undergoes an immediate (<1 min) sol-gel transition at 37 °C. In situ hydrogel formation at 37 °C was also observed after intravitreal injection of the formulation into an ex vivo rabbit eye. The hydrogel network formation was due to physical self-assembly of the PNIPAM blocks and a catalyst-free furan-maleimide Diels−Alder (DA) chemical crosslinking in the hydrophobic domains of the polymer network. Rheological studies demonstrated sol-gel transition at 23 °C, and DA crosslinks were formed in time within 60 min by increasing the temperature from 4 to 37 °C. When incubated at 37 °C, these hydrogels were stable for at least one year in phosphate buffer of pH 7.4. However, the gels degraded at basic pH 10 and 11 after 13 and 3 days, respectively, due to hydrolysis of ester bonds in the crosslinks of the hydrogel network. The hydrogel was loaded with an anti-VEGF antibody fragment (FAB; 48.4 kDa) or with corticosteroid dexamethasone (dex) by dissolving (FAB) or dispersing (DEX) in the hydrogel precursor solution. The FAB fragment in unmodified form was quantitatively released over 13 days after an initial burst release of 46, 45 and 28 % of the loading for the 5, 10 and 20 wt% hydrogel, respectively, due to gel dehydration during formation. The low molecular weight drug dexamethasone was almost quantitively released in 35 days. The slower release of dexamethasone compared to the FAB fragment can likely be explained by the solubilization of this hydrophobic drug in the hydrophobic domains of the gel. The thermosensitive gels showed good cytocompatibility when brought in contact with macrophage-like mural cells (RAW 264.7) and human retinal pigment epithelium-derived (ARPE-19) cells. This study demonstrates that PNF-PNM thermogel may be a suitable formulation for sustained release of bioactive agents into the eye for treating posterior segment eye diseases.

A 4‐Arm PEG‐Thiodepsipeptide Precursor Enables Gelatinase‐Promoted Hydrogel Formation

AbstractIn situ hydrogelation of injectable precursors upon biological stimulus is relevant to generate hydrogels under mild conditions and, potentially, at a biological side of interest. Here, it is shown that hydrolytic enzymes can be used to initiate the formation of covalent hydrogel networks, realizing a cleavage‐leading‐to‐gelation strategy. For this purpose, a two‐component system is used, consisting of a 4‐arm polyethylene glycol‐thiodepsipeptide conjugate, PEG4TDPo containing the matrix metalloproteinases MMP‐2‐ and MMP‐9‐cleavable Ac‐Pro‐Leu‐Gly#SLeu‐Leu‐Gly‐ thiodepsipeptide sequence releasing a thiol upon hydrolysis, and a maleimide functionalized 4‐armed PEG (PEG4MAL). PEG4TDPo is synthesized in a PEG‐functionalization protocol involving convergent and divergent synthetic steps without the need for rigorous purification procedures. In a fluorometric assay, it is shown that the construct is in fact cleaved by both investigated MMPs. PEG4TDPo in the presence of 10 wt.% PEG4MAL formed hydrogels upon addition of MMP‐2 or ‐9 with average gelation times of 28 and 40 min, respectively, as is investigated by rheology. The much faster gelation times compared to the enzyme‐free system showed the specific input of the enzymatic reactions. The MMP‐assisted activation and crosslinking strategy can potentially become useful by targeting tissues showing an increased expression of MMPs, such as cancers, or to detect MMPs.

A self-assembled dynamic extracellular matrix-like hydrogel system with multi-scale structures for cell bioengineering applications

Extracellular matrix (ECM) provides various types of direct interactions with cells and a dynamic environment, which can be remodeled through different assembly/degradation mechanisms to adapt to different biological processes. Herein, through introducing polyphosphate-modified hyaluronic acid and bioactive glass (BG) nano-fibril into a self-assembled hydrogel system with peptide-polymer conjugate, we can realize many new ECM-like functions in a synthetic polymer network. The hydrogel network formation is mediated by coacervation, followed by a gradual transition of peptide structure from α-helix to β-sheet. The ECM-like hydrogels can be degraded through a number of orthogonal mechanisms, including treatments with protease, hyaluronidase, alkaline phosphatase, and calcium ion. As 2D coating, the ECM-like hydrogels can be used to modify the planar surface to promote the adhesion of mesenchymal stromal cells, or to coat the cell surface in a layer-by-layer fashion to shield the interaction with the substrate. As ECM-like hydrogels for 3D cell culture, the system is compatible with injection and cell encapsulation. Upon incorporating fragmented electrospun bioactive glass nano-fibril into the hydrogels, the synergetic effects of soft hydrogel and stiff reinforcement nanofibers on recapitulating ECM functions result in reduced cell circularity in 3D. Finally, by injecting the ECM-like hydrogels into mice, gradual degradations over a time period of one month and high biocompatibility have been shown in vivo. The contribution of complex network dynamics and hierarchical structures to cell-biomatrix interaction can be investigated multi-dimensionally, as many mechanisms are orthogonal to each other and can be regulated individually. STATEMENT OF SIGNIFICANCE: A list of native ECM features has attracted the most interest and attention in the research of synthetic biomaterials. In this research, we have described a simple ECM-like hydrogel system in which the complex and elegant functions of native ECM can be recapitulated in a chemically defined synthetic system. The ECM-like hydrogel systems were developed to avoid undesired features of biological substances (e.g., ethical concerns, batch-to-batch variation, immunogenicity, and potential risk of contamination), as well as gaining new functions to facilitate bioengineering applications (e.g., 3D cell culture, injection, and high stability). To this end, we have developed an ECM-like hydrogel system and provide evidence that this purely synthetic biomaterial is a promising candidate for cell bioengineering applications.

Development, characterization and In-vitro evaluation of guar gum based new polymeric matrices for controlled delivery using metformin HCl as model drug.

Currently, hydrogels are considered as ideal biomaterials due to their unique structure and characteristics that facilitates considerable hydrophilicity, swelling, drug loading and release. In this study, we report pH-responsive GG-MAA-AMPS hydrogel delivery system prepared via free radical polymerization technique. Hydrogels were loaded with Metformin HCl as a model drug. Hydrogels were characterized through Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). FTIR confirmed the successful crosslinking of reactants, hydrogel network formation and drug loading. TGA and DSC proved the higher thermal stability of reactants after crosslinking and drug loading. XRD analysis showed decrease in crystallinity of drug after loading into the hydrogels. SEM revealed smooth and glassy appearance of both loaded and unloaded hydrogels. Gel content was increased with increase in concentration of reactants. Drug entrapment was decreased by increasing concentration of GG and AMPS while MAA acted inversely. Hydrogels displayed pH-dependent swelling and drug release behavior being high at pH 6.8 and 7.4 while low at acidic pH (1.2). Oral tolerability in rabbits showed that hydrogels were safe without causing any hematological or histopathological changes in healthy rabbits. Based on the obtained results, GG-MAA-AMPS can be considered as potential carrier for metformin HCl as well as other hydrophilic drugs.

Robust and highly adaptable high internal phase gel emulsions stabilized solely by a natural saponin hydrogelator glycyrrhizic acid.

Herein, we report a new class of high internal phase gel emulsions (gel-HIPEs) that are mechanically robust, adaptable, and processable. They can be synthesized facilely by using the natural food-grade saponin glycyrrhizic acid (GA) as the sole stabilizer, which is shown to be versatile for various oils. The structural properties of these HIPEs including appearance, viscoelasticity and processability are well controlled by simply changing the concentration of GA nanofibrils. When the GA nanofibril concentration exceeds 0.3 wt%, the unique gel-HIPEs can be produced through the formation of fibrillar hydrogel networks in the continuous phase. When the nanofibril concentration only increases to 5 wt%, it is surprising to see that these gel-HIPEs display an extremely high mechanical strength, and the storage moduli as well as the yield stress values can reach 408.5 kPa and 3340 Pa (or even more), respectively. We conjecture that such remarkable mechanical performance is mainly attributed to the highly viscoelastic GA nanofibrillar networks in the continuous phase of gel-HIPEs, which can actively trap the nanofibril-coated emulsion droplets and thus strengthen the gel matrix. Consequently, the robust gel-HIPEs can be used as a solid template to fabricate stable porous materials without the need for crosslinking of the continuous phase, and the open- and closed-cell foam microstructures are controlled by the nanofibril concentration. Furthermore, the nanofibril-based HIPEs are promising long-term delivery vehicles with controlled-release properties for lipophilic active cargoes, since the strong fibrillar networks at the droplet surfaces and in the continuous phase can effectively retard the active release.

Crosslinked hydrogels of polyethylenimine and graphene oxide to treat Cr(VI) contaminated wastewater

This research papers reports the synthesis of graphene oxide (GO) and polyethylenimine (PEI) based crosslinked nanocomposite hydrogels (GO/PEI-NCH) for its application as potential adsorbent to treat Cr(VI) polluted water. To synthesize GO/PEI-NCH, graphene oxide was initially amine functionalized using 3-aminopropyltriethoxysilane (APTES) which was subsequently grafted with PEI. Successful functionalization of GO with APTES and the crosslinked hydrogel network formation was evidenced by characterizing samples using SEM, X-ray diffraction, Raman, FTIR and TGA. Approximately 97% Cr(VI) was adsorbed from the chromium solution of 50 mg/L concentration at pH 2 with 0.5 g/L mass of GO/PEI-NCH. Further, adsorption isotherm correlated well with Langmuir model and predicted homogenous monolayer adsorption with the adsorbent having energetically identical binding sites. GO/PEI-NCH exhibited 443.8 mg/g maximum adsorption capacity for Cr(VI). Adsorption kinetics was well defined using pseudo-second-order model. GO/PEI-NCH could be easily and efficiently regenerated using HCl solution and it exhibited good stability and reusability for ten continuous adsorption-desorption cycles. Therefore, GO/PEI-NCH is a promising candidate to treat Cr(VI) ions contaminated wastewater.

Removal of heavy metal ions from an aqueous solution by CS/PVA/PVP composite hydrogel synthesized using microwaved-assisted irradiation

A simple protocol of chitosan/polyvinyl alcohol/polyvinylpyrrolidone (CS/PVA/PVP) hydrogel synthesis using microwave-assisted irradiation to initiate and accelerate network formation was explored. The optimum ratio of CS:PVA:PVP was 0.3:0.6:0.3 g with epichlorohydrin as a cross-linking agent under 600 watts of irradiation for 3 min. The gel swelling degree and gel fraction of the hydrogel were approximately 1627.4% and 42.6%, respectively. The individual metal ion removal efficiency was the highest for Pb(II), followed by Cu(II), Ni(II), and Cd(II) as adsorbed by the CS/PVA/PVP hydrogel. Varying the pH of the solution containing metal ions in the range of 4.0 – 8.0 did not significantly affect the adsorption capacity. However, the order of adsorption capacity of mixed metal ions differed from that of individual ions. The maximum capacities of Pb(II), Cu(II), Ni(II), and Cd(II) ions were 80.02, 33.07, 15.13, and 8.36 mg g−1, respectively. The desorption and reusability study of the CS/PVA/PVP hydrogel revealed that 0.1 M EDTA was a suitable candidate to regenerate the hydrogel as more than 60% of metal ion removal efficiency was still achieved after five adsorption cycles. In addition, the reaction mechanism of the hydrogel network formation derived from infrared spectrometry indicated that network formations were developed through the reaction between the crosslinking agent and hydroxyl and amino functional groups of the starting materials. Adsorption mechanism based on the results obtained from x-ray photoelectron spectroscopy (XPS) and x-ray absorption spectroscopy (XAS) was also presented. This study showed that the proposed composite hydrogel could be further developed and used as a platform to efficiently adsorb metal ions.

Antibacterial Properties and pH Sensitive Swelling of Insitu Formed Silver-Curcumin Nanocomposite Based Chitosan Hydrogel.

A simple method was used to prepare curcumin/silver nanocomposite based chitosan hydrogel. In an alkaline medium, chitosan and chitosan nanocomposite hydrogels were prepared using the physical crosslinking method. The prepared hydrogels were stable for a long period at room temperature. In one step, silver nanoparticles were prepared insitu using silver nitrate solution and curcumin oxide within the hydrogel network formation. In the meantime, curcumin compound served as both a reducing and stabilizing agent. The structure and surface morphology of nanocomposite hydrogels were characterized by FTIR, SEM, and EDX analysis confirmed the formation of silver nanoparticles within the hydrogel network. Moreover, Images of TEM showed a spherical shape of silver nanoparticles with an average size of 2–10 nm within the matrix of the hydrogel. The formation mechanism of nanocomposite based hydrogel was reported. Besides that, the effect of chitosan and silver nitrate concentrations were studied. The swelling capacity of the prepared nanocomposite hydrogels was also performed at different pH of 4, 7, and 9. From the experimental results, the swelling capacity of hydrogels depends on the concentrations of chitosan and silver nitrate. The prepared composite based hydrogel exceeds a higher swelling degree than chitosan hydrogels at low pH. The antibacterial activity of the nanocomposite hydrogels was also examined; the results showed that the prepared nanocomposite hydrogels outperformed the pure chitosan hydrogels. This shows them to be a promising material for the biomedical field as a wound dressing and drug release.

Self-assembly and hydrogel formation ability of Fmoc-dipeptides comprising \u03b1-methyl-L-phenylalanine

Various biofunctional hydrogel materials can be fabricated in aqueous media through the self-assembly of peptide derivatives, forming supramolecular nanostructures and their three-dimensional networks. In this study, we describe the self-assembly of new Fmoc-dipeptides comprising α-methyl-L-phenylalanine. We found that the position and number of methyl groups introduced onto the α carbons of the Fmoc-dipeptides by α-methyl-L-phenylalanine have a marked influence on the morphology of the supramolecular nanostructure as well as the hydrogel (network) formation ability.

In situ forming hydrogel for sustained intraocular drug delivery

AbstractPurposeDelivery of therapeutic proteins to the posterior segment of the eye faces significant challenges because of frequent intraocular injections, related adverse effects and high treatment costs. This research project aims to design in situ forming hydrogels, which can be easily injected in the vitreous cavity using a small needle. After injection, the polymeric solution undergoes a phase transition to form a cross‐linked hydrogel at the site of administration, entrapping bioactives, which will be released over a prolonged period. In this study, Hyaluronic acid‐modified with furan moieties (HAFU) was successfully crosslinked with four arm‐PEG10K‐maleimide (4APM) yielding stable hydrogels. The potential use of this system for ocular applications was shown by testing the injectability, sustained release of a therapeutic protein and cytocompatibility to retinal cells.Methods &amp; ResultsHAFU‐4APM hydrogels were prepared by mixing an aqueous solution of HAFU and 4APM at physiological conditions to obtain transparent hydrogels. Rheological analysis showed rapid hydrogel network formation at 37°C. The gelation time and final hydrogel stiffness are strongly dependent on polymer concentration. Hydrogel solutions could be injected to the vitreous body of a porcine eye through a 29G needle. Swelling and degradation analysis showed that the hydrogel system is degradable at physiological conditions. The hydrogels showed no toxicity to retinal cells at the used concentrations. HAFU‐4APM hydrogels could sustain the delivery of bevacizumab for 71 days.ConclusionInjectable in situ forming hydrogels have been prepared for the sustained retinal delivery of bevacizumab. The formulation has potential for the treatment of age‐related macular degeneration and diabetic retinopathy.AcknowledgementsThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.

A facile and low-cost route for producing a flexible hydrogel–PANI electrolyte/counter electrode applicable in dye-sensitized solar cells (DSSC)

In this work, hybrid hydrogels were prepared based on poly(acrylic acid-co-acrylamide) hydrogels (Gel) and self-assembled nanostructured polyaniline (PANI). These hybrid hydrogels were prepared by in situ UV-assisted aniline polymerization during hydrogel network formation in a controlled interfacial reaction. They were then tested as flexible quasi-solid electrolytes with a counter electrode in dye-sensitized solar cells. This electrolyte-counter electrode system was prepared on top of a titanium dioxide layer deposited on a transparent and conductive anode electrode (ITO). Three different nanostructured Gel–PANI hybrid hydrogels were fabricated by employing different PANI concentrations and used for constructing electrolyte–counter electrode systems that displayed conductivities between 0.003 S/cm and 0.02 S/cm. Dye-sensitized solar cells (DSSC) that had the configuration ITO/TiO2/Gel–PANI/ITO were prepared and tested using natural dye extracted from Myrciaria cauliflora. The energy conversion efficiency was evaluated under AM1.5 (100 mW/cm2) light irradiation and was found to reach values above 2.0%. The device’s energy conversion efficiency was found to be higher than those of others with the same natural dye. The process proved to be fast and facile, and it utilized an inexpensive natural dye.

A Natural Supramolecular Saponin Hydrogelator for Creation of Ultrastable and Thermostimulable Food‐Grade Foams

AbstractA new class of food‐grade foams that are ultrastable, thermostimulable, and processable can be created simply by using the naturally occurring saponin glycyrrhizic acid (GA) as the sole stabilizer. The creation of this “superfoam” is based on the spatially controllable self‐assembly of supramolecular GA nanofibril hydrogelators at the air–water interface and in the continuous phase. The rapid adsorption of GA nanofibrils at the bubble surface, forming a multilayer interfacial network, combined with the formation of viscoelastic fibrillar hydrogel networks in the continuous phase, enables the foams having ultrastability over months or years without the water drainage induced phase separation, which have been evidenced using small angle X‐ray scattering and microscopy techniques. Such ultrastable foams can be rapidly destabilized on demand by heating, which induces the melting of the fibrillar networks. These thermoresponsive foams can be reversibly switched between stable and unstable by simply changing the temperature, based on the reversible gel–sol phase transition of the supramolecular hydrogel inside the foam. This is the first finding of a natural edible surfactant system that foams very well and can be used solely to make advanced foams with the qualities of simplicity, ultrastability, stimulability, and processability, which make them viable for many sustainable applications.

Development of a simple coarse-grained DNA model for analysis of oligonucleotide complex formation

In this paper, we develop a coarse-grained nucleotide model for the purpose of simulating large-scale aptamer-based hydrogel network formation in future research. In the model, each nucleotide is represented by a single interaction site containing sugar, phosphate and base. Discontinuous molecular dynamics (DMD) simulations are performed to simulate formation and denaturation of oligonucleotide duplexes as a function of temperature. The simulated melting temperatures of oligonucleotide duplexes are calculated in simulations of systems with different sequences, lengths and concentrations of oligonucleotides, and compared to data from the OligoAnalyzer tool. The denaturation of oligonucleotide triplexes containing a hybridised structure of three different oligonucleotides is analysed using both simulations and experiments. The nucleotide model is found to be a good predictor of the oligonucleotide’s hybridised state for both duplexes and triplexes. This coarse-grained model has wide ranging applications in the development or optimisation of DNA-based technologies including DNA origami, DNA-enabled hydrogels and DNA-based biosensors.

Synthesis and characterization of a novel pH-responsive nanocomposite hydrogel based on chitosan for targeted drug release

Over the last decade, nanocomposite hydrogels have been provided a new approach for the biomedical field. In this work, a novel pH-responsive nanocomposite hydrogel was fabricated using simultaneous in situ formation of magnetite iron oxide nanoparticles and hydrogel networks of poly(acrylic acid) grafted onto chitosan. The effects of various types of precursor molecules, pH, salt, and loading pressure were examined on the swelling properties of resulting nanocomposite hydrogels. The synthesized nanocomposite hydrogel was well characterized using different instruments. In vitro drug releasing behavior of doxorubicin was studied at pH 5.4 and 7.4. The drug release mechanism was investigated through different kinetic models. These experimental results open a new opportunity to make pH-responsive nanocomposite hydrogel devices for controlled delivery of drug.

Poly(N-isopropylacrylamide) grafting solution parameters for controlling temperature responsiveness in PET membranes fabricated using 248 nm KrF excimer laser

A fast, simple, and efficient method to fabricate thermo-responsive membranes using 248 nm KrF excimer laser has been reported. For that process, monomer and crosslinker concentration effects on hydrogel network formation were studied during 248 nm pulsed laser polymerization (PLP) of poly(N-isopropylacrylamide) (PNIPAM) on laser ablated polyethylene terephthalate (PET) membranes. Water permeability of over 6 orders could be easily achieved, at room temperature, by appropriately tuning the hydrogel network parameters. The network growth could be controlled by reducing the monomer and crosslinker concentrations in the grafting solution. Caffeine diffusion studies established that controlled amounts of a model drug could be transported across the membranes. Crosslinker concentration had a more pronounced effect on the temperature responsivity of the grafted network across the lower critical solution temperature (LCST) of PNIPAM. A transition from positive to reverse temperature responsiveness was also observed for highly crosslinked grafted networks. Quantitative ATR-FTIR studies were performed to evaluate the relative amount of PNIPAM grafted in the membranes which was correlated to chain growth in pulsed laser polymerization.

Loratadine-Loaded Thermoresponsive Hydrogel: Characterization and Ex-vivo Rabbit Cornea Permeability Studies.

Poor bioavailability of ophthalmic drops is mainly due to drainage through the nasal-lacrimal duct and a very low permeability through corneal epithelium. The aim of our study was to prepare and characterize an ocular hydrogel of loratadine, as an example of a lipophilic drug, to increase drug concentration and residence time at the site of action in the eye. In this study, a 23 full factorial design was employed to design and compare the properties of eight different loratadine containing hydrogel formulations. Results showed a significant correlation between the swelling and porosity ratios of the hydrogels and the Pluronic percentage and Pluronic/carbomer ratio in the formulations. Moreover, the release profiles showed fast and sustained release of all the formulations. Evaluation of hydrogels structure by the FT-IR technique indicated that Pluronic interacts with hydroxyl and carboxylic groups in carbomer, which is the main reason of the hydrogel network formation and interacts with loratadine.The permeation of loratadine through rabbit cornea showed that drug permeation percentages for the F2 and F7 formulations were 15 and 70 folds more than that of the control.

Dynamic Coordination of Eu-Iminodiacetate to Control Fluorochromic Response of Polymer Hydrogels to Multistimuli.

New fluorochromic materials that reversibly change their emission properties in response to their environment are of interest for the development of sensors and light-emitting materials. A new design of Eu-containing polymer hydrogels showing fast self-healing and tunable fluorochromic properties in response to five different stimuli, including pH, temperature, metal ions, sonication, and force, is reported. The polymer hydrogels are fabricated using Eu-iminodiacetate (IDA) coordination in a hydrophilic poly(N,N-dimethylacrylamide) matrix. Dynamic metal-ligand coordination allows reversible formation and disruption of hydrogel networks under various stimuli which makes hydrogels self-healable and injectable. Such hydrogels show interesting switchable ON/OFF luminescence along with the sol-gel transition through the reversible formation and dissociation of Eu-IDA complexes upon various stimuli. It is demonstrated that Eu-containing hydrogels display fast and reversible mechanochromic response as well in hydrogels having interpenetrating polymer network. Those multistimuli responsive fluorochromic hydrogels illustrate a new pathway to make smart optical materials, particularly for biological sensors where multistimuli response is required.