Structure and properties of polysaccharide nanocrystal-doped supramolecular hydrogels based on Cyclodextrin inclusion

Polysaccharide nanocrystals, such as the rod-like whiskers of cellulose and chitin, and platelet-like starch nanocrystals, were for the first time incorporated into supramolecular hydrogels based on cyclodextrin/polymer inclusion in order to enhance mechanical strength and regulate drug release behavior. The structures and properties of the resultant nanocomposite hydrogels were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and rheological testing. As expected, the elastic modulus of the nanocomposite hydrogels climbed, owing to the reinforcing function of the polysaccharide nanocrystals. The modulus of the cellulose whisker-doped hydrogel was 50 times higher than that of the native hydrogel. Furthermore, the presence of polysaccharide nanocrystals increased the stability of the hydrogel framework and inhibited the diffusion of bovine serum albumin, which served as a model protein drug in the nanocomposite hydrogels and showed prominent sustained release profiles. Importantly, the incorporation of polysaccharide nanocrystals did not show additional cytotoxicity as comparison with the native hydrogel. In addition, the inherited shear-thinning property of the nanocomposite hydrogels contributed to their potential as injectable biomaterials.     

Sustained release behavior of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogels containing activated carbon fibers

The composites of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogel and activated carbon fibers (ACFs) were prepared as sustained drug release system with excellent mechanical properties. The mechanical properties of hydrogels were improved greatly by addition of ACFs. The thinner ACFs were more effective in increasing the mechanical properties of composite hydrogels. The cumulative amount of release and the release period were dependent on the surface area and the pore volume of ACFs. The drug release was maximized at basic condition due to the pH‐sensitive hydrogel matrices and the initial bust phenomenon was alleviated by incorporating ACFs in the hydrogels. The drug release was sustained about four times longer and the mechanical property was increased about 2.6 times higher because ACFs worked as drug reservoir and reinforcement. Cytotoxicity evaluation confirmed the biocompatible characteristics of the ACFs‐containing hydrogels. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Poly(vinyl alcohol)/chitosan/honey/clay responsive nanocomposite hydrogel wound dressing

Many efforts have been made to develop modern wound dressings to overcome limitations of traditional ones. Smart nanocomposite hydrogels are appropriate candidates. In this work, a novel responsive nanocomposite hydrogel based on poly(vinyl alcohol)/chitosan/honey/clay was developed and evaluated as a novel wound dressing. The morphology and properties of synthesized nanocomposite hydrogels loaded with honey as a drug model were investigated. The exfoliated morphology of nanocomposite was confirmed by X‐ray diffractometry. Swelling studies were performed at 20 and 37 °C at various pH. The results showed that swelling increased as a result of temperature rise and maximum swelling occurred at a pH of 2. In vitro release of honey was also studied at the same conditions. Corresponding results indicated faster honey release rate at higher pH values. MTT results exhibited no cytotoxicity in nanocomposite hydrogel system. Investigation of antibacterial activity revealed more than 99% antibacterial activity for proposed system. In vivo results confirmed the wound healing ability of developed system. Generally, appropriate properties of proposed system made it ideal in wound dressing applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46311.     

A Carbodiimide Cross-Linked Silk Fibroin/Sodium Alginate Composite Hydrogel with Tunable Properties for Sustained Drug Delivery

Carbodiimide cross-linked silk fibroin (SF)/sodium alginate (SA) composite hydrogels with superior stability and tunable properties are developed by varying preparation parameters. SF/SA blend ratio modulation allows to achieve composite hydrogel gelation times of 18–65 min, and rheological analysis shows that the speed of gel formation, the hydrogel network's density, and the hydrogels’ compressive properties are closely related to the blend ratio. The G′ of different hydrogels varies substantially from 28 to 413 Pa, and the hydrogel with higher SF content has a greater stiffness. The composite hydrogels present appropriate porosity of 76.63–85.09% and pore size of 316–603 µm. Hydrogel stability improves significantly after cross-linking, and substantial swelling occurs due to the hydrophilicity of SA. The 7/3 and 6/4 SF/SA hydrogels are more resistant to degradation in PBS, and cytotoxicity testing confirmed their biocompatibility. For release studies in vitro, two model compounds are used as drug models, tetracycline hydrochloride, and bovine serum albumin (BSA). Different ratios of SF/SA have a greater influence on the release of BSA. This study provides a practical preparation method for flexible SF/SA composite hydrogels, which can help design hydrogels with specific physicochemical properties for different applications, especially drug delivery.     

An Insight on the Swelling,Viscoelastic, Electrical,and Drug Release Properties of Gelatin–Carboxymethyl Chitosan Hydrogels

The present study reports the in-depth analysis of the gelatin–carboxymethyl chitosan hydrogels. The composite system formed phase-separated hydrogels, which is confirmed by scanning electron microscopy. The swelling of the carboxymethyl chitosan-containing hydrogels was lower than the gelatin hydrogel. Macroscale deformation study using a static mechanical tester indicated a viscoelastic nature of the hydrogels. A decrease in the impedance of the hydrogels was observed with an increase in the carboxymethyl chitosan content. The drug release from the hydrogels was predominantly Fickian diffusion mediated and was released in its active form. The results suggested the potential use of the hydrogels as drug delivery matrices.     

Gelatin based pH‐sensitive hydrogels for colon‐specific oral drug delivery: Synthesis,characterization, and in vitro release study

Based on gelatin (Gltn) and acrylic acid (AAc), biodegradable pH‐sensitive hydrogel was prepared using gamma radiation as super clean source for polymerization and crosslinking. Incorporation of PAAc in the prepared hydrogel was confirmed by Fourier transform infrared spectroscopy (FTIR). The effect of PAAc content on the morphological structure of the prepared hydrogel swollen at pH 1, 5, and 7 was examined using scanning electron microscopy (SEM). The results showed the dependence of the porous structure of the prepared hydrogels on AAc content and the pH of the swelling medium. Swelling properties of gelatin/acrylic acid copolymer hydrogels with different AAc contents were investigated at different pH values. Swelling data showed that the prepared hydrogels possessed pronounced pH sensitivity. In vitro release studies were performed to evaluate the hydrogel potential as drug carrier using ketoprofen as a model drug. Experimental data showed that the release profile depends on both hydrogel composition and pH of the releasing medium. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Controlled release of Montelukast Sodium from pH-sensitive injectable hydrogels

pH sensitive hydrogels showed excellent drug release properties, with promise for other biomedical applications. Also, the impact of molecular weight (MW) and degree of deacetylation (DDA) of chitosan on the fabricated chitosan/poly (vinyl alcohol) (3:1 mol ratio) hydrogel with selective silane crosslinker amount was evaluated for controlled drug delivery. The FTIR spectroscopy confirmed the incorporated components and the developed interactions among the polymer chains. The hydrogel characteristics were expressed by their responsive behaviour in different environments (water, ionic media and pH). The hydrogel sample (CH1000) having chitosan with higher MW and DDA exhibited more thermal stability and bacterial growth inhibition against E.coli. All hydrogels exhibited maximum swelling at basic and neutral pH and less swelling was observed in acidic media. For drug release analysis performed in simulated gastric fluid, hydrogel showed controlled drug release in 2 h but it was more than 10%, consequently cannot be used for oral purpose. In simulated intestinal fluid, hydrogels exhibited more than 80% release within 90 min. This characteristic phenomenon at neutral pH empowered hydrogel appropriate towards injectable and targeted controlled release of applicable drug. It was concluded that the prepared hydrogel can be administered directly into the venous circulation through syringe and can be used with better results for biomedical applications.     

Effect of different modified lignins on the properties of xylan composite hydrogels

To improve the mechanical properties of hemicellulose hydrogel, a green, adjustable mechanical property, high swelling ratio (SR) composite hydrogel was successfully prepared by using modified lignin as a reinforcing agent. The structure and characteristics of the composite hydrogels were investigated by TGA, FTIR, SEM, rheological analysis, and SR. It can be found that the modified lignin could significantly improve the mechanical properties of the composite hydrogels. The maximum compressive stress of unmodified lignin hydrogel was 61.72 kPa and the compressive deformation was 75%. Compared with the unmodified lignin hydrogel, the mechanical properties were significantly improved, with the maximum compressive stress of the modified lignin hydrogel was 145.2 kPa and the compressive deformation was up to 90%. After adding modified lignin, the SR of the as-prepared hydrogel was up to 155.17 g/g, which was much higher than that of unmodified lignin hydrogel (105.79 g/g). The composite hydrogel had good antioxidant properties, and the free radical removal rate can reach 85.3%, which is twice as much as that without the modified lignin. With cost-effective lignin as a reinforcing agent, the as-prepared hemicellulose hydrogel with adjustable mechanical properties is favorable for great application potential.     

Temperature/pH/magnetic triple‐sensitive nanogel–hydrogel nanocomposite for release of anticancer drug

Hydrogels, nanogels and nanocomposites show increasing potential for application in drug delivery systems due to their good chemical and physical properties. Therefore, we were encouraged to combine them to produce a new compound with unique properties for a long‐term drug release system. In this regard, the design and application of a nanocomposite hydrogel containing entrapped nanogel for drug delivery are demonstrated. To this aim, we first prepared an iron oxide nanocomposite nanogel based on poly(N‐isopropylacrylamide)‐co‐((2‐dimethylaminoethyl) methacrylate) (PNIPAM‐co‐PDMA) grafted onto sodium alginate (NaAlg) as a biocompatible polymer and iron oxide nanoparticles (ION) as nanometric base (PND/ION‐NG). This was then added into a solution of PDMA grafted onto NaAlg. Through dropwise addition of mixed aqueous solution of iron salts into the prepared polymeric solution, a novel hydrogel nanocomposite with excellent pH, thermal and magnetic responsivity was fabricated. The synthesized samples were fully characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy with energy‐dispersive X‐ray analysis, vibrating sample magnetometry and atomic force microscopy. A mechanism for the formation of PNIPAM‐co‐PDMA/NaAlg‐ION nanogel–PDMA/NaAlg‐ION hydrogel and PND/ION nanogel is suggested. Swelling capacity was measured at various temperatures (25 to 45 °C), pH values (from 2 to 11) and magnetic field and under load (0.3 psi) and the dependence of swelling properties of the nanogel–hydrogel nanocomposite on these factors was well demonstrated. The release rate of doxorubicin hydrochloride (DOX) as an anticancer drug was studied at different pH values and temperatures in the presence and absence of a magnetic field. The results showed that these factors have a high impact on drug release from this nanocomposite. The result showed that DOX release could be sustained for up to 12.5 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or nanogel alone (<1 day). The results indicated that the nanogel–hydrogel nanocomposite can serve as a novel nanocarrier for anticancer drug delivery. © 2019 Society of Chemical Industry     

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.     

Polyvinyl alcohol/chitosan/carbon nanotubes electroactive shape memory nanocomposite hydrogels

Shape memory nanocomposite hydrogels are intelligent soft materials in which, the nanoparticles can impart desirable mechanical properties to the polymeric matrix. The main challenge is the capability to program from permanent to temporary shapes and vice versa under the direct and indirect thermal stimuli. In this work, carbon nanotubes (CNT) with a high modulus of 1 TPa, was used to mechanically reinforce polyvinyl alcohol (PVA) and polyvinyl alcohol/chitosan (PVA/Cs) hydrogel networks. Adding appropriate amount of conductor component enables the system to be electrically activated, which leads to achieving the original permanent shape without applying mechanical external force. The PVA/Cs/CNT hydrogel containing 0.25 wt% of CNT, showed electrical conductivity greater than 9 mS cm⁻¹. Because of the presence of CNT, the shape memory behavior of PVA and PVA/Cs hydrogels was improved by 170 and 260%, respectively. The electroactive shape memory nanocomposite hydrogels exhibited complete recovery under indirect stimulation by generating Joule heating in the system.     

Poly(sodium 4-styrene sulfonate) and poly(2-acrylamidoglycolic acid) nanocomposite hydrogels: montmorillonite effect on water absorption,thermal, and rheological properties

A systematic study of water absorbency, thermal, and rheological properties was performed on nanocomposite hydrogels of poly(sodium 4-styrene sulfonate) (PSSNa) and poly(2-acrylamide glycolic acid) (PAAG). Montmorillonite was used as clay filler and was previously modified to hydrogel synthesis by addition of (3-acrylamide propyl)trimethylammonium chloride. Syntheses were carried out by in situ radical polymerization, using N,N-methylen-bis-acrylamide as crosslinker reagent. Nanocomposites showed an exfoliated morphology, confirmed by transmission electron microscopy and X-ray diffraction. The water absorption capacity (WAC) of unloaded PSSNa hydrogel was three times higher than for PAAG; due to clay addition, absorption capacity increased for PSSNa nanocomposites and decreased for PAAG. Finally, rheological properties of nanocomposite hydrogels were studied by both dynamic oscillatory test and shear creep analysis. Results showed improvements on mechanical properties, such as yield point, elastic recovery, and storage modulus as consequence of montmorillonite addition.     

Construction and evaluation of the hydroxypropyl methyl cellulose-sodium alginate composite hydrogel system for sustained drug release

We prepared a hydroxypropyl methyl cellulose-sodium alginate (HPMC-SA) composite hydrogel with a membrane covering the semi-interpenetrating network based on a semi-synthetic polymer hydroxypropyl methyl cellulose (HPMC) and a natural polymer sodium alginate (SA) by Ca²⁺ crosslinking and polyelectrolyte complexation with chitosan (CS) covering the hydrogel surface. The physiochemical properties of HPMC-SA hydrogels were evaluated by scanning electron microscopy, infrared spectrum, X-ray diffraction, and thermogravimetric analysis. The swelling ratio of the HPMC-SA composite hydrogel in simulated gastrointestinal fluid was measured. The drug release behavior of the HPMC-SA composite hydrogel for macro-molecular and small-molecule drugs was evaluated by using bovine serum albumin, metformin hydrochloride, and indomethacin as model drugs. The results showed that the HPMC-SA hydrogel had good water absorption and degradability, an increased swelling ratio of 55, and a prolonged time for maximum swelling degree of 50 h. Moreover, the hydrogel exhibited higher drug-loading capacity and improvements in the sustained release of bio-macromolecules, demonstrating its potential as a drug carrier for biomedical applications.     

A rechargeable drug delivery system based on pNIPAM hydrogel for the local release of curcumin

This study was designed to develop a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) hydrogel and a suitable solvent to enhance solubility and local release of curcumin. pNIPAM hydrogel was synthesized by radical polymerization. The chemical, mechanical and physical properties and biocompatibility of pNIPAM hydrogel were investigated as an implantable and rechargeable drug reservoir. Curcumin was loaded within pNIPAM hydrogel during swelling by using two different solvents; methanol, an organic solvent, and low molecular weight polyethylene glycol (PEG200), a polymeric solvent. The results of drug solubility showed that using PEG200 can increase curcumin solubility more than commonly used organic solvents such as methanol. Also, the release profile of drug-loaded hydrogels demonstrated that PEG200 has a superior effect on the cumulative amount of released curcumin (33.163 ± 0.319 μg/ml) compared to methanol (8.765 ± 0.544 μg/ml) during 1 week. Based on our results, curcumin-loaded hydrogels did not show any cytotoxicity, and pNIPAM/PEG combination represented an antibacterial effect within 12 hours. Accordingly, it can be concluded that pNIPAM hydrogel in combination with low molecular weight PEG200 could be used as an efficient drug delivery system to preserve and provide sustained release of curcumin as a hydrophobic drug.     

On the preparation and swelling properties of hydrogel nanocomposite based on Sodium alginate-g-Poly (acrylic acid-co-acrylamide)/Clinoptilolite and its application as slow release fertilizer

A novel slow release fertilizer hydrogel nanocomposite was prepared via free radical polymerization of sodium alginate, acrylic acid, acrylamide, and clinoptilolite using N, N?-methylene bisacrylamide as a crosslinker and ammonium persulfate as an initiator. Evidence of grafting and component interactions was obtained by a comparison of the Fourier transform infrared spectra of the initial substrates and hydrogel without clinoptilolite with that of the hydrogel nanocomposite containing clinoptilolite. The swelling behavior of both hydrogels in solutions of various pHs (2-12) and various saline solutions such as NaCl, KCl, CaCl₂ and FeCl₃ as well as swelling kinetics were investigated. Results showed that the swelling of hydrogels depends on the solution pH value. Also, the swelling of both hydrogels in all salt solutions is significantly lower than that of the values in distilled water. After those characterizations, the potential application was verified through sorption and fertilizer releasing from the hydrogel with and without clinoptilolite zeolite. The presence of the clinoptilolite zeolite in the hydrogel caused the system to liberate the nutrient in a more controlled manner than that with the neat hydrogel. The results of the fertilizer release of hydrogel nanocomposite were also encouraging in order to find applications in agriculture. Consequently, the good slow release fertilizer property as well as the good water adsorption capacity showed that this formulation is potentially viable to be used in agriculture as a nutrient carrier vehicle.     

Carboxymethyl sago pulp/carboxymethyl sago starch hydrogel: Effect of polymer mixing ratio and study of controlled drug release

Carboxymethyl sag o pulp (CMSP)/carboxymethyl sago starch (CMSS) hydrogel was synthesized by electron beam irradiation. In the series of hydrogels prepared, 40%/20% CMSP/CMSS hydrogel had the highest gel fraction. The swelling capacity of CMSP/CMSS hydrogel was found to be highest in distilled water, followed by pH 11, pH 7.4, and pH 1.2. Scanning Electron Microscope photographs revealed that the drug‐loaded hydrogel had a smoother surface than unloaded hydrogel. Fourier Transform Infrared and Differential Scanning Calorimetry analysis showed the absence of interaction between the hydrogels and the drug. All drug‐loaded hydrogels had drug encapsulation efficiency between 63% and 69%. CMSP/CMSS hydrogel swelled and allowed the release of drug at pH 7.4. These properties qualify the hydrogel as a potential candidate for controlled drug release at the ocular and colonic regions. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43652.     

Effect of graphene oxide on the pH-responsive drug release from supramolecular hydrogels

Polypseudorotaxane (PPR) hydrogels formed by inclusion complexes between poly(ethylene glycol) (PEG) and α-cyclodextrin (α-CD) are highlighted as promising biomaterial for drug delivery. Here, we report a novel injectable PPR hydrogel containing graphene oxide (GO) for pH-responsive controlled release of doxorubicin hydrochloride (DOX). Our results showed that the gelation rates of the PEG/α-CD supramolecular structures could be tailored depending on the reagent concentrations. The formation of PEG/α-CD inclusion complexes was confirmed by TEM and XRD, the latter further confirming that GO restricts their formation. The supramolecular hydrogels were easily loaded with DOX by simple addition into the PEG solution before the complex formation with the α-CD solution. Noteworthy, disruption of ionic interactions between DOX and GO in the nanocomposite at pH = 5.5 resulted in higher DOX release than under physiological conditions (pH = 7.4). This pH dependence was barely observed in pure PPR hydrogel. These findings introduce DOX-loaded supramolecular hydrogels nanocomposites as promising carriers for pH-responsive and therefore localized, drug delivery systems.     

Electroresponsive and spinnable hydrogels from xanthan gum and gelatin enhanced by Fe3+ ions coordination

Polyelectrolyte hydrogels with spinnability and electroresponsive were prepared from xanthan gum (XG) and gelatin. Oscillatory rheological measurements were utilized to explore mechanical properties and thermal stability of the resultant XG-Gelatin5 hydrogels. The XG-Gelatin5 hydrogels possessed higher strength and larger critical strain than these of the XG hydrogels, demonstrating existence of synergistic interactions. The XG-Gelatin5 hydrogels were stable in temperature range of 20–60°C, and gradually release drug with controlled manner in neutral and acid medium at 37°C. The self-recoverable and thixotropic XG-Gelatin5 hydrogels were extruded to form hydrogel fibers, and the dried hydrogel fibers rapidly bend towards cathode under applied voltage. Long hydrogel fibers were harvested with enhancement by Fe³⁺ ions, and were weaved and braided to obtain hydrogel fiber constructs. The XG-Gelatin5 hydrogel fibers with electroresponsive and controlled drug release possess potential applications in biomaterials, tissue engineering, and drug carrier fields.     

Polypropylene oxide/polyethylene oxide-cellulose hybrid nanocomposite hydrogels as drug delivery vehicle

This article deals with the synthesis of hybrid nanocomposite hydrogels through the combination of cellulose (C), polypropylene oxide/poly ethylene oxide (PPO/PEO), and silver nanoparticles (AgNPs) by in situ polymerization technique for the in vitro release of ornidazole drugs. The structure of the resulted materials is identified using SEM, XRD, FTIR, XPS, and TGA spectroscopic techniques. The resulting structure, morphology, thermo responsive property, water retention, and swelling behavior of hydrogels are investigated. The rheological measurement is studied to establish the enhancement of the viscoelasticity and stiffness of hydrogels. The antibacterial activity of the biodegradable silver hybrid nanocomposite hydrogel is investigated by inhibition zone method against gram positive and negative bacteria. Maximum drug release of 96.4% is recorded at 7.4 pH in 5 h. The biocompatibility and cytotoxicity of the hybrid nanocomposite hydrogel are verified using mouse fibroblast cell line L-929 (ATCC CCL-1) cells for their possible use as controlled drug delivery vehicles. The nontoxic nature makes the materials more biocompatible and suitable to apply in the biological systems. Therefore, nontoxic and biocompatible natures of present materials with improved thermal and rheological properties support for their possible uses as drug delivery vehicles.     

APPARENT NON-FICKIAN RELEASE FROM A SCLEROGLUCAN GEL MATRIX

Hydrogels, and particularly biopolymeric hydrogels, have recently received tremendous interest as controlled release systems for their peculiar features such as high biocompatibility, biodegradability, bioadhesivity, chemical and thermal resistance and good mechanical properties. Among biopolymers, the exocellular microbial polysaccharide scleroglucan appears to be particularly well suited for the formulation of monolithic hydrogel matrices for controlled drug release. In this work we studied the macroscopic factors influencing the kinetics of a model drug release (theophylline) from a scleroglucan hydrogel matrix (2%w/w) and modeled the relevant experimental results. The evidences for the release experiments indicate that the kinetics of the processes follow an apparently non-Fickian behavior under different active drug concentration, temperature and stirring speed. However, by considering the peculiar nature of the hydrogel matrix and the geometrical features of the experimental setup in the formulation of the appropriate initial and boundary conditions, data can be satisfactorily modeled with the classical Fick's law.