Modulate the phase transition temperature of hydrogels with both thermosensitivity and biodegradability

The synthesis and characterization of thermoresponsive hydrogels on the basis of N-isoproplyarylamide (NIPAAm) and acrylamide (AAm) copolymers crosslinked with a novel biodegradable crosslinker (PEG-co-PLA) were carried out in this study. Swelling measurement results demonstrated that four gels of PNAM5, PNAM10, PNAM12 and PNAM15 are thermoresponsive. The equilibrium swelling ratio and degradation of the hydrogels strongly depend on hydrogels composition. The morphology of the hydrogels was observed by scanning electron microscopy (SEM), and their thermal property was characterized by differential scanning calorimetry (DSC). The results show that the proportion of AAm in the copolymer has notable effect on the low critical solution temperature (LCST) of the hydrogel. When the molar ratio of AAm to NIPAAm was increased from 1:10 to 3:10 the LCST of the copolymer increased from 39.7 to 64.2 °C. The compression modulus of PNAM15 is of the highest among other hydrogels, because PNAM15 hydrogel has a more compact structure.     

Synthesis and characterization of chondroitin sulfate–methacrylate hydrogels

The various degree of methacrylate (MA) substitution on chondroitin sulfate (CS) was prepared by reacting chondroitin sulfate with methacrylic anhydride (MAA) in the presence of sodium hydroxide (NaOH) as a base. The effects of reaction time, reaction temperature, MAA concentration, and NaOH amount on the substitution degree of CS-MA were tested. The confirmation of the CS-MA chemical structure was carried out by ¹H-NMR, ¹³C-NMR, FTIR and the degree of MA substituent on CS was calculated from the ratios of two peak intensities corresponding to methyl groups on methacrylate and chondroitin sulfate, respectively. Hydrogels were prepared by free radical polymerization of CS-MA precursors with or without acrylic acid (AA). CS-MA hydrogels were easily broken into small pieces during swelling study. However, CS-MA-AA hydrogels remained completely and showed a range of swelling ratio from 200 to 390% and exhibited an increase in swelling ratio with a decreasing degree of MA substitution. The thermal degradability observed with a TGA explained the unstableness of these hydrogels in comparison with the pure CS. The surface morphology conducted by SEM exhibited a porous structure after swelling.     

Cell adhesion and proliferation on poly(N-vinylacetamide) hydrogels and double network approaches for changing cellular affinities

Poly(N-vinylacetamide) hydrogels (PNVA gels) were synthesized to investigate their basic characteristics for biomedical applications such as water contact angles, protein uptake, and mouse fibroblasts (L-929) cell adhesion. Because PNVA gels show hydrophilic features, double network (DN) hydrogels were prepared by the secondary polymerization of N-vinylacetamide (NVA) or acrylamide (AAm) in PNVA gels (NVA/NVA DN gels and NVA/AAm DN gels, respectively), in order to vary PNVA gel features for biocompatibility. Contact angles for both DN gels decreased to around 20 degrees, whereas both PNVA and PAAm gels were over 30 degrees. On the other hand, more protein tended to adsorb to DN gels than single network hydrogels. Compared to PNVA gel, cell adhesion and proliferation on NVA/NVA DN gel were improved with less swelling ratio and much protein uptake, while no significant difference was observed on NVA/AAm DN gel, probably due to more hydrophilic character, supported by lowest water contact angle. These complicated structure change in DN gels would provide a new methodology for tuning the biocompatibility of hydrogels and for controlling surface hydrophilic characteristics and network structures.     

Synthesis and characterization of hydrogels based on grafted chitosan for the controlled drug release

Temperature and pH-responsive hydrogels based on chitosan grafted with poly acrylic acid (PAAc), poly hydroxy propyl methacrylate (PHPMA), poly (vinyl alcohol) (PVA) and gelatin were prepared for controlled drug delivery. These stimuli-responsive hydrogels were synthesized by gamma irradiation technique. The degree of gelation was over 90% and increased as chitosan, AAc and PVA content increased, while the degree of gelation decrease with the increase of gelatin content. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of 2–9 was investigated. An increase of swelling degree with an increase in the pH was noticed and showed the highest value at pH 9. Also antibiotic drug Oxttetracycline was loaded into the hydrogels and the release studies were carried out at different pH and temperature. The in vitro release profiles of the drug showed that, the release of the drug increased as the time, temperature and pH increased and reached to maximum after 48 h at pH 9. The prepared hydrogels were characterized by using SEM, FTIR, and DSC.     

IPNs based on chitosan with NVP and NVP/HEMA synthesised through photoinitiator-free photopolymerisation technique for biomedical applications

Biocompatible interpenetration polymeric network (IPN) hydrogels based on chitosan with N-vinylpyrrolidinone (NVP) as well as its copolymer with 2-hydroxymethyl methacrylate (HEMA) were synthesised using the photopolymerisation technique without the inclusion of any photoinitiator or crosslinking agent. These hydrogels were characterised using the Fourier-transform infrared spectroscopy (FTIR) technique. Equilibrium swelling of these hydrogels was performed in Milli-Q water and drug release studies were carried out using theophylline as the model drug. These tests showed that the IPN comprised of chitosan and NVP with a very small amount of N-hydroxymethyl maleimide (HMMI) included exhibited higher swelling abilities and fast drug release rates than the IPN which contained chitosan, NVP and HEMA. Kinetic studies of water diffusion into these hydrogels and drug release revealed that with the exception of the IPN with HEMA incorporated, the other hydrogels did not adhere to the Fickian diffusion model. These hydrogels were tested for their biocompatibility with human epidermal keratinocyte cells (HaCaT). A positive cell growth as evidenced by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay indicated that these hydrogels are non-toxic to human keratinocytes and can be potentially used as biomaterials for biomedical applications.     

Characterization and in vitro evaluation of starch based hydrogels as carriers for colon specific drug delivery systems

A series of starch/methacrylic acid (MAAc) copolymer hydrogels of different compositions were synthesized using γ-rays induced polymerization and crosslinking. The effects of the preparation conditions such as the feed solution concentration, feed solution composition and irradiation dose on the gelation process of the synthesized copolymer were investigated. The swelling behavior of the starch/methacrylic acid (MAAc) copolymer hydrogels was characterized by studying the effect of the hydrogel composition on the time- and pH-dependent swelling. Swelling kinetics showed that the synthesized hydrogels possessed Fickian diffusion behavior at pH 1 and non-Fickian diffusion at pH 7 which recommend them as good candidate for colon specific drug delivery systems. The synthesized hydrogels were loaded with ketoprofen as a model drug to investigate the release behavior of the synthesized hydrogels. The results showed the ability of the hydrogels to keep the loaded drug at pH 1 and release it at pH 7. The data also showed that the release rate can be controlled by controlling the preparation conditions such as comonomer concentration and composition and irradiation dose.     

Radiation crosslinked psyllium and polyacrylic acid based hydrogels for use in colon specific drug delivery

In order to utilize the psyllium husk, a medicinally important natural polysaccharide, to develop the hydrogels meant for the drug delivery, we have prepared psyllium and polyacrylic acid based polymeric networks by radiation-induced crosslinked copolymerization. Polymeric networks (hydrogels) thus formed were characterized with SEMs, FTIR and swelling studies. Swelling behavior of the hydrogels was studied as a function of monomer concentration in the hydrogels and temperature, pH and [NaCl] of the swelling medium. This paper discusses the swelling kinetics of the hydrogels and release dynamics of anticancer model drug 5-fluorouracil from the hydrogels for the evaluation of swelling and drug release mechanisms. It has been observed from the release dynamics of drug that diffusion exponent ‘n’ have 0.7, 0.8 and 0.7 values and gel characteristics constant ‘k’ have 9.13 × 10⁻³, 6.22 × 10⁻³ and 9.01 × 10⁻³ values for the release of 5-fluorouracil, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer. The values of the diffusion exponent show that the release of drug from drug-loaded hydrogels has occurred through Non-Fickian diffusion mechanism. It has also been observed from the swelling and release of drug in the different pH buffer that the polymer matrix is pH responsive and can be exploited for the delivery of anticancer drug to the colon.     

Synthesis and characterization of some cellulose/chondroitin sulphate hydrogels and their evaluation as carriers for drug delivery

Mixed hydrogels based on natural, biodegradable and biocompatible polysaccharides, such as cellulose (C) and chondroitin sulphate (CS) in various mixing ratios were prepared by a crosslinking technique and characterized by swelling behaviour, FTIR spectroscopy, scanning electron microscopy, toxicity and biocompatibility tests.The mixed cellulose/chondroitin sulphate hydrogels have been loaded with 7-[2-nitroxiacetyl-oxy-3-(4-acetyl-amino-phenoxy)-propyl]-8-morpholino-1,3-dimethyl-xanthine, a novel nitric oxide donor compound with a lower toxicity and a higher anti-inflammatory activity than its parent molecules, paracetamol and theophylline. Swelling and release kinetics have been also studied. It has been established that an increase of CS content in hydrogels composition leads to a higher swelling ratio for all formulations and to a decreased released amount of nitric oxide donor compound. It has been found that the swelling occurs by an anomalous swelling mechanism, while the release of nitric oxide donor compound follows a diffusion controlled mechanism.     

Electric Field-Controlled Benzoic Acid and Sulphanilamide Delivery from Poly(Vinyl Alcohol) Hydrogel

The controlled release of benzoic acid (3.31 Å) and sulphanilamide (3.47 Å) from poly(vinyl alcohol), PVA, hydrogels fabricated by solution casting at various cross-linking ratios, were investigated. The PVA hydrogels were characterized in terms of the degree of swelling, the molecular weight between cross-links, and the mesh size. The drug release experiment was carried out using a modified Franz diffusion cell, at a pH value of 5.5 and at temperature of 37°C. The amount of drug release and the diffusion coefficients of the drugs from the PVA hydrogels increased with decreasing cross-linking ratio, as a larger mesh size was obtained with lower cross-linking ratios. With the application of an electric field, the amount of drug release and the diffusion coefficient increased monotonically with increasing electric field strength, since the resultant electrostatic force drove the ionic drugs from the PVA matrix. The drug size, matrix pore size, electrode polarity, and applied electric field were shown to be influential controlling factors for the drug release rate.KEY WORDS: electrophoresis force, ionic drug delivery, iontophoresis, poly(vinyl alcohol)     

Investigation of PVA/ws-chitosan hydrogels prepared by combined γ-irradiation and freeze-thawing

γ-Irradiation combined with freeze-thawing, i.e. irradiation followed by freeze-thawing and freeze-thawing followed by irradiation, was applied to prepare poly(vinyl alcohol) (PVA)/water soluble chitosan (ws-chitosan) hydrogels for wound dressing. The properties of these hydrogels were investigated and compared to those prepared by freeze-thawing and by irradiation, respectively. Hydrogels made by irradiation followed by freeze-thawing show larger swelling capacity and mechanical strength, higher thermal stability, lower water evaporation rate, and are less turbid than those made by pure freeze-thawing and freeze-thawing followed by irradiation. Hydrogels made by irradiation alone cannot be used as wound dressing due to their poor mechanical strength. SEM results show that the final structure of hydrogels made by combined irradiation and freeze-thawing is mainly determined by the first processing step. It is found that the appropriate amount of ws-chitosan can endow hydrogels with large swelling capacity and mechanical strength. The presence of ws-chitosan provides the hydrogels with good antibacterial activity against Escherichia coli (E. coli).     

Drug loading into and drug release from pH- and temperature-responsive cylindrical hydrogels

Hydrogels that undergo deformation upon appropriate changes in pH or temperature have considerable promise as drug delivery vehicles. Drug uptake in swelling and nonswelling cylindrical hydrogels and drug release from these into a target fluid are investigated here. A mathematical model for hydrogel-solution composite, a composite of a distributed parameter system (cylindrical hydrogel) and a lumped parameter system (surrounding solution), is developed. The polymer network displacement in a swelling/deswelling hydrogel is described by a stress diffusion coupling model. The analytical solution for network displacement is used to predict solvent intake by swelling hydrogels, solvent efflux from deswelling hydrogels, and changes in pressure, porosity, and effective drug diffusivity. These in turn influence drug uptake during and after hydrogel swelling and drug release from hydrogel during and after deswelling. Numerical results illustrate benefits of hydrogel swelling for drug loading and merits of different modes of drug release. Drug uptake and drug release by temperature-responsive hydrogels are compared with those by hydrogels not subject to deformation.     

Preparation, characterization and properties of aminoethyl chitin hydrogels

Aminoethyl chitins (AEC) with different amino contents were synthesized from chitin and 2-chlorethylamine hydrochloride, and the AEC hydrogels were prepared by crosslinking with glutaraldehyde. The microstructures, swelling behaviors and antibacterial activities of the hydrogels were investigated. The results of Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance ((1)H NMR) spectrum and scanning electron microscopy (SEM) showed that the hydrogels were prepared by forming the Schiff base from AEC and glutaraldehyde. The aminoethyl chitin hydrogels were sensitive to acidic environment. The swelling ratio changed with the amino content of AEC, declined with the increase of the crosslinking agent concentration and increased with the increase of the AEC concentration. In addition, the antibacterial results of the hydrogels against Staphylococcus aureus (S. aureus) indicated that the hydrogels had good antibacterial activities, and the antibacterial properties were affected by the amino content of AEC and the crosslinking agent concentration.     

Synthesis, characterization and swelling studies of pH responsive psyllium and methacrylamide based hydrogels for the use in colon specific drug delivery

In order to utilize the psyllium husk a medicinally important natural polysaccharide and to develop the novel hydrogels meant for the colon specific drug delivery, we have prepared psyllium and methacrylamide based polymeric networks by using N,N′-methylenebisacrylamide (NN-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator. To study various structural aspects of the polymeric networks thus formed psy-cl-poly(MAAm), these were characterized with SEMs, FTIR, TGA and swelling studies. The swelling studies of networks were carried out as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both composition of the polymer and nature of swelling medium. Maximum percent swelling 1262 was observed for the polymeric network prepared with 19.45 × 10⁻³ mol/L of [NN-MBAAm] at 40 °C in 0.5 M NaOH solution. This article also discusses the release dynamics of tetracycline hydrochloride from the hydrogels, for the evaluation of the drug release mechanism and diffusion coefficients of drug from the polymer matrix. The effect of pH on the release pattern of tetracycline hydrochloride has been studied by varying the pH of the release medium. It has been observed from the release dynamics of drug from the hydrogels that the diffusion exponent ‘n’ have 0.477, 0.423 and 0.427 values and gel characteristic constant ‘k’ have 5.07 × 10⁻², 6.34 × 10⁻² and 6.38 × 10⁻² values, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer solution. The values the ‘n’ indicated that the Fickian type diffusion mechanism occurred for the release of tetracycline hydrochloride from drug loaded psy-cl-poly(MAAm) polymers in different release mediums. In Fickian type diffusion mechanism, the rate of polymer chain relaxation is more as compare to the rate of drug diffusion from these hydrogels and release behavior follows Fick’s law of diffusion. In each release medium, the values of the initial diffusion coefficient ‘D_i’ for the release of tetracycline hydrochloride was higher than the values of late time diffusion coefficient ‘D_L’ indicating that in the start, the diffusion of drug from the polymeric matrix was faster as compare to the latter stages.     

Characterization of photo-cross-linked oligo[poly(ethylene glycol) fumarate] hydrogels for cartilage tissue engineering

Photo-cross-linkable oligo[poly(ethylene glycol) fumarate] (OPF) hydrogels have been developed for use in tissue engineering applications. We demonstrated that compressive modulus of these hydrogels increased with increasing polymer concentration, and hydrogels with different mechanical properties were formed by altering the ratio of cross-linker/polymer in precursor solution. Conversely, swelling of hydrogels decreased with increasing polymer concentration and cross-linker/polymer ratio. These hydrogels are degradable and degradation rates vary with the change in cross-linking level. Chondrocyte attachment was quantified as a method for evaluating adhesion of cells to the hydrogels. These data revealed that cross-linking density affects cell behavior on the hydrogel surfaces. Cell attachment was greater on the samples with increased cross-linking density. Chondrocytes on these samples exhibited spread morphology with distinct actin stress fibers, whereas they maintained their rounded morphology on the samples with lower cross-linking density. Moreover, chondrocytes were photoencapsulated within various hydrogel networks. Our results revealed that cells encapsulated within 2-mm thick OPF hydrogel disks remained viable throughout the 3-week culture period, with no difference in viability across the thickness of hydrogels. Photoencapsulated chondrocytes expressed the mRNA of type II collagen and produced cartilaginous matrix within the hydrogel constructs after three weeks. These findings suggest that photo-cross-linkable OPF hydrogels may be useful for cartilage tissue engineering and cell delivery applications.     

Synthesis of antibacterial PVA/CM-chitosan blend hydrogels with electron beam irradiation

A series of excellent hydrogels were prepared from poly(vinyl alcohol) (PVA) and carboxymethylated chitosan (CM-chitosan) with electron beam irradiation (EB) at room temperature. Electron spectroscopy analysis of the blend hydrogels revealed that good miscibility was sustained between CM-chitosan and PVA. The properties of the prepared hydrogels, such as the mechanical properties, gel fraction and swelling behavior were investigated. The mechanical properties and equilibrium degree of swelling improved obviously after adding CM-chitosan into PVA hydrogels. The gel fraction determined gravimetrically showed that a part of CM-chitosan was immobilized onto PVA hydrogel. The further analyses of FTIR and DSC spectra of the prepared gels after extracting sol manifested that there was a grafting interaction between PVA and CM-chitosan molecules under irradiation. The antibacterial activity of the hydrogels against Escherichia coli was also measured via optical density method. The blend hydrogels exhibited satisfying antibacterial activity against E. coli, even when the CM-chitosan concentration was only 3 wt%.     

Interpenetrating biopolymer network based hydrogels for an effective drug delivery system

Discovery of hydrogels has resulted in developing competent controlled-release drug delivery systems. Present study describes the synthesis and characterization of novel pH responsive hydrogels of chitosan, hydroxyl ethyl cellulose (HEC) and polyol prepared by physical blending of the three components in different ratios. Vegetable oil derived polyol seems to act as a filler and cross linking agent. The synthesized hydrogels were characterized using FT-IR spectroscopy, thermo gravimetric analysis (TGA), Optical microscopy and scanning electron microscopy (SEM). Equilibrium swelling behavior of hydrogels in water and different buffers with pH values (2, 4, 7.3, and 8) indicated the sustained expansion of the films in different pH solutions.     

Modification of Okra mucilage with acrylamide: Synthesis, characterization and swelling behavior

In the present communication, the synthesis and characterization of Okra mucilage, a food grade and water-soluble polysaccharide, based-materials are described. Okra mucilage has been modified by grafting acrylamide (AAm) for developing the new green polymeric materials of specialty applications. Grafting has been done under N₂ atmosphere using redox initiator and hydrogels were prepared by using N,N-methylenebisacrylamide (NN-MBAAm) as crosslinker. The effect of monomer concentration, initiator concentration, reaction time and temperature in terms of grafting efficiency (%GE), percent grafting (PG) and percent gel (%G) has been investigated. The grafted polymers and hydrogels were characterized by SEM, XRD and FTIR techniques to study various structural aspects. The swelling behavior of the crosslinked polymeric material has also been studied as a function of time, temperature and pH. The application area of these polymers is varied from biomaterials to the wastewater treatment.     

Synthesis of a novel superabsorbent hydrogel by copolymerization of acrylamide and cashew gum modified with glycidyl methacrylate

Novel superabsorbent hydrogels were manufactured using chemically modified cashew gum (CGMA) and acrylamide (AAm) as reactants. The route for the synthesis was feasible due to the incorporation of glycidyl methacrylate (GMA) into structure of cashew gum (CG) to form the cashew gum-methacrylated (CGMA), in an appropriate mixture water-DMSO, as solvent, and using TEMED as catalyst. Thereafter, the CGMA was copolymerized with AAm yielding (CGMA-co-AAm) hydrogels. The main characteristics of raw and the modified materials are reported in this paper. ¹³C NMR, ¹H NMR and FTIR spectroscopies confirmed the incorporation of vinyl groups, from GMA, into CG structure. By the spectrophotometry analyses, it was found that, ca. 82% of GMA was incorporated to the CG after 24 h of reaction. The cross-linking of CGMA or co-polymerization of CGMA with acrylamide leads to a hydrogel formation. Their gelation was characterized by FT-IR analysis. Alkaline hydrolysis at 40 °C for 3 and 4.5 h increased the water uptake (WU) capacity. Hydrolyzed CGMA-co-AAm hydrogels present higher values of WU (up to 1500) and may be classified as water superabsorbent material. Applications in agriculture, as soil conditioner, and in biomedical field, as biomaterial (scaffold) are being investigated.     

Synthesis and characterization of pH-sensitive hydrogel composed of carboxymethyl chitosan for colon targeted delivery of ornidazole

In the present study, carboxymethyl chitosan was prepared from chitosan, crosslinked with glutaraldehyde and evaluated in vitro as a potential carrier for colon targeted drug delivery of ornidazole. Ornidazole was incorporated at the time of crosslinking of carboxymethyl chitosan. The chitosan was evaluated for its degree of deacetylation (DD) and average molecular weight; which were found to be 84.6% and 3.5×10(4) Da, respectively. The degree of substitution on prepared carboxymethyl chitosan was found to be 0.68. All hydrogel formulations showed more than 85% and 74% yield and drug loading, respectively. The swelling behaviour of prepared hydrogels checked in different pH values, 1.2, 6.8 and 7.4, indicated pH responsive swelling characteristic with very less swelling at pH 1.2 and quick swelling at pH 6.8 followed by linear swelling at pH 7.4 with slight increase. In vitro release profile was carried out at the same conditions as in swelling and drug release was found to be dependant on swelling of hydrogels and showed biphasic release pattern with non-fickian diffusion kinetics at higher pH. The carboxymethylation of chitosan, entrapment of drug and its interaction in prepared hydrogels were checked by FTIR, (1)H NMR, DSC and p-XRD studies, which confirmed formation of carboxymethyl chitosan from chitosan and absence of any significant chemical change in ornidazole after being entrapped in crosslinked hydrogel formulations. The surface morphology of formulation S6 checked before and after dissolution, revealed open channel like pores formation after dissolution.     

Chemical and physical factors in design of antibiofouling polymer coatings

Because most "low fouling" polymers resisting bacterial attachment are hydrophilic, they are usually also significantly swollen. Swelling leads to purely physical dilution of interaction and weakens attachment; however, these nonspecific contributions are usually not separated from the specific effect of polymer chemistry. Taking advantage of the fact that chemistry and swelling of hydrogels may be independently varied through the fraction of a cross-linker, the roles of chemistry and physical dilution (swelling) in bacterial attachment are analyzed for selected hydrogels. Using as a quantitative indicator the rate of bacterial deposition in a parallel plate setup under defined flow conditions, the observed correlation of deposition rate with swelling provides a straightforward comparison of gels with different chemistries that can factor out the effect of swelling. In particular, it is found that chemistry appears to contribute similarly to bacterial deposition on hydrogels prepared from acrylamide and a zwitterioninic monomer 2-(methacryloyloxy)ethyl) dimethyl-(3-sulfopropyl) ammonium hydroxide so that the observed differences may be related to swelling only. In contrast, these gels were inferior to PEG-based hydrogels, even when swelling of the latter was lower, indicating a greater contribution of PEG chemistry to reduced bacterial deposition. This demonstrates that swelling must be accounted for when comparing different biofouling-resistant materials. Chemical and physical principles may be combined in hydrogel coatings to develop efficient antibiofouling surfaces.