Poly(hydroxyethyl methacrylate)-based co-polymeric hydrogels for transdermal delivery of salbutamol sulphate

Various co-polymeric hydrogels for transdermal delivery of salbutamol sulphate were synthesized using 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MAA) and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) in the presence of ammonium persulphate (APS) and N,N,N′,N′-tetramethylethylenediamine (TEMED) as redox free radical initiator and ethyleneglycol dimethacrylate (EGDMA) as a cross-linker. The synthesized co-polymeric hydrogels were characterized using FT-IR spectral studies and swelling studies. It was observed that percentage swelling of co-polymeric hydrogel increased with the increasing concentration of DMAPMA and methacrylic acid. Salbutamol sulphate, a well-known vasodilator, was labeled with ^99mTc(technetium) and loaded on circular discs of various hydrogels. In vitro permeation of radiolabelled salbutamol sulphate was carried out using a Franz diffusion cell in phosphate-buffered saline (PBS, pH 7.4) as dissolution medium through mice skin. It was observed that drug release from the co-polymeric hydrogel carriers increased on increasing the amount of DMAPMA in the polymeric carriers, while it decreased on increasing the amount of MAA content. The local toxicity studies of DMAPMA-containing hydrogel patches were carried out in rabbits. Drug-loaded patches applied on rabbit skin showed no toxicity, even after 1 week of studies.     

Poly(γ-glutamic acid) modulates the properties of poly(ethylene glycol) hydrogel for biomedical applications

In this paper, a series of copolymer hydrogels were fabricated from methacrylated poly(γ-glutamic acid) (mPGA) and poly(ethylene glycol) diacrylate (PEGDA). The effect of ionic strength and pH on the swelling behavior and mechanical properties of these hydrogels were studied in detail. Release of Rhodamine B as a model drug from the hydrogel was evaluated under varied pH. In vitro photoencapsulation of bovine cartilage chondrocytes was performed to assess the cytotoxicity of this copolymer hydrogel. The results revealed that the copolymer hydrogel is ionic- and pH-sensitive, and does not exhibit acute cytotoxicity; this copolymer hydrogel may have promising application as matrix for controlled drug release and scaffolding material in tissue engineering.     

PEG-g-chitosan thermosensitive hydrogel for implant drug delivery: cytotoxicity,in vivo degradation and drug release

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL^?1. After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration.     

Temperature-sensitive PVA/PNIPAAm semi-IPN hydrogels with enhanced responsive properties

A series of temperature-sensitive hydrogels of semi-interpenetrating polymeric networks (semi-IPN) composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly(vinyl alcohol) (PVA) were prepared by radical polymerization. The PNIPAAm networks were cross-linked by N,N'-methylenebisacrylamide in the presence of linear PVA. The reaction processes were investigated by rheometry using oscillatory deformation tests. It was found that gelations were very fast and the modulus reached equilibrium within about 12.5min. The prepared semi-IPN hydrogels were characterized for their morphologies and thermal behaviors by scanning electron microscopy and differential scanning calorimetry, respectively. The interior network structures of the semi-IPN matrix became more porous with increasing PVA. In comparison to the conventional PNIPAAm gel, the newly reported semi-IPN hydrogels exhibited the same lower critical solution temperature. Their swelling properties, such as temperature dependence of equilibrium swelling ratio, shrinking kinetics and reswelling kinetics in water, were also studied. Experimental data indicated that the shrinking and reswelling rates of the semi-IPN hydrogels were much faster than those of the conventional PNIPAAm hydrogels. With this novel approach, water absorption and response properties could be adjusted by tuning the feed ratio of NIPAAm and PVA. These fast responsive hydrogels exhibited improved temperature sensitivity and swelling properties compared to the conventional PNIPAAm hydrogel, which would be critical and desirable for a gel to find potential applications in biomedical fields, such as drug delivery systems and sensors.     

Magnetic/pH-sensitive κ-carrageenan/sodium alginate hydrogel nanocomposite beads: preparation,swelling behavior,and drug delivery

This work describes the preparation of magnetic and pH-sensitive beads based on κ-carrageenan and sodium alginate for use as drug-targeting carriers. Physical cross-linking using K⁺/Ca²⁺ ions was applied to obtain ionic cross-linked magnetic hydrogel beads. The produced magnetite beads were thoroughly characterized by TEM, SEM/EDS, XRD, FTIR, and VSM techniques. While the water absorbency (WA) of magnetic beads was enhanced by increasing the weight ratio of κ-carrageenan, introducing magnetic nanoparticles caused a decrease in WA capacity from 15.4 to 6.3 g/g. Investigation on the swelling of the hydrogel beads in NaCl, KCl, and CaCl₂ solutions revealed the disintegration of beads depending on the composition of hydrogel beads and the type of metal cations in swelling media. The swelling ratio of beads indicated pH-dependent properties with maximum water absorbing at pH 7.4. Also, it was found that the strength of pH-sensitivity of magnetic beads was low for beads with the high content of carrageenan component. The in vitro drug release studies from hydrogels exhibited significant behaviors on the subject of physiological-simulated pH values and external magnetic fields. The maximum cumulative releases obtained were 98 and 43% at pH values 7.4 and 1.2, respectively. The Introducing magnetite nanoparticles influenced the cumulative release of drug.     

Preparation and Enhancing Properties of pH-Sensitive Hydrogel in Light of Gum Ghatti-cl-poly(acrylic acid)/ – o-MWCNT for Sodium Diclofenac Drug Release

Gum ghatti (GG) is used as a biopolymer, acrylic acid (AA) is used as a synthetic monomer, ammonium persulphate (APS) is used as an initiator, and methylene bis-acrylamide (MBA) is used as a cross-linker in the current study to create gum ghatti-cl-poly(acrylic acid)-o-MWCNT hydrogels. The –o-MWCNT (0, 10, 20, 30, 40, and 50 mg) is added to the hydrogel as a filler. Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analyses are used to characterize the crosslinked hydrogels. The successful polymerization of the graft is confirmed by these spectroscopic studies. Sodium diclofenac (SD) as a model drug is utilized. Swelling tests are also conducted at pH 6.8 on all prepared hydrogels. In a similar manner, all hydrogel preparations are subjected to an in vitro study at neutral (pH 7.4), acidic (pH 1.2), and basic (pH 9.2) mediums, and a higher drug release is observed at pH 7.4. The Higuchi model, the Korsmeyer–Peppas model, and various zero-order and first-order kinetics are utilized in the investigation of the drug release order mechanism from the hydrogels. The drug release data favor the Korsmeyer–Peppas model, which describes the “n” diffusion exponent that controls the drug release mechanism from synthesized hydrogels. The “n” values control the Fickian diffusion (Case-I diffusional) like coupled diffusion (0.45 ≤ n). According to the results presented here, GGAACNT-based hydrogels can be used in biomedical fields, especially for controlled drug release.     

Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel with pH-responsive release

Hyaluronic acid (HA) is made up of repeating disaccharide units (β-1,4-d-glucuronic acid and β-1,3-N-acetyl-d-glucosamine) and is a major constituent of the extracellular matrix. HA and its derivatives which possess excellent biocompatibility and physiochemical properties have been studied in drug delivery and tissue engineering applications. Tyramine-based HA hydrogel with good compatibility to cell and tissue has been reported recently. However, inferior mechanical property may limit the biomedical application of the HA hydrogel. In this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared through a horseradish peroxidase catalyzed in situ cross-linking process. As compared with pure HA hydrogels, incorporation of GO to the HA matrix could significantly enhance the mechanical properties (storage moduli 1800 Pa) of the hydrogel and prolong the release of rhodamine B (RB) as the model drug from the hydrogel (33?h) as well. In addition, due to the multiple interactions between GO and RB, the NC hydrogels showed excellent pH-responsive release behavior. The release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the presence of GO, which could be attributed to the enhanced interactions between GO and HA as well as with RB. In situ three-dimensional encapsulation of mouse embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity results indicated the cytocompatibility of both the enzymatic cross-linking process and HA/GO NC hydrogels (cell viability 90.6 ± 4.25%). The enzymatically catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and had great potential in the construction of both tissue engineering scaffolds and stimuli-responsive drug release matrices.     

Modified carrageenan. 2. Hydrolyzed crosslinked κ-carrageenan-g-PAAm as a novel smart superabsorbent hydrogel with low salt sensitivity

A novel pH-responsive superabsorbing hydrogel based on κ-carrageenan (κC) was prepared through polyacrylamide crosslinking grafting followed by alkaline hydrolysis. The hydrogel structure was confirmed using FT-IR spectroscopy. The hydrolysis conditions were systematically optimized to obtain a hydrogel with maximum swelling capacity. Thus, the reaction variables, including the hydrolysis time and temperature, concentration of sodium hydroxide, amount of hydrogel hydrolyzed and post-neutralization pH, were optimized. The swelling measurements of the hydrogels were conducted in 0.15 M aqueous solutions of LiCl, NaCl, KCl, CaCl₂ and AlCl₃. As observed for the hydrolyzed hydrogel (H-carragPAM), it was found that a 'charge screening' action of small cations and carboxylate anions affected the swelling in univalent salt solutions. In the case of the non-hydrolyzed hydrogel (carragPAM), however, a converse trend was observed. As a result, carragPAM and H-carragPAM superabsorbent hydrogels showed a maximum swelling of 45 and 135 g/g in LiCl and KCl solutions, respectively. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as anti-salt superabsrbents. The swelling of superabsorbing hydrogels was examined in buffer solutions with pH values ranging between 1 and 13. The H-carragPAM hydrogel exhibited a pH-responsie character so that a swelling-deswelling pulsatile behavior was recorded at pH 4 and 9. The swelling kinetics of H-carragPAM were preliminary investigated.     

Synthesis,Swelling and Drug-Release Behaviour of a Poly(N,N-diethylacrylamide-co-(2-dimethylamino) ethyl methacrylate) Hydrogel

In this study, poly(N,N-diethylacrylamide-co-(2-dimethylamino) ethyl methacrylate) (poly(DEA-co-DMAEMA)) hydrogels were synthesized by changing the initial DEA/DMAEMA mol ratio. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). In comparison with the PDEA hydrogel, the equilibrium swelling ratio (ESR) and lower critical solution temperature (LCST) of the hydrogels increase with the increase of DMAEMA content in the feed. The deswelling and reswelling kinetics and cytotoxicity of the different composition ratios of DEA to DMAEMA in the co-polymerized hydrogels were also investigated in detail. The absorption and release behaviour of the model drug, bovine serum albumin, were found to be dependent on hydrogel composition and environment temperature, which suggests that these materials have potential application as intelligent drug carriers.     

Porous Agarose-Based Semi-IPN Hydrogels: Characterization and Cell Affinity Studies

Abstract

Hydrogels are frequently considered for medical applications due to the ease of preparation in different forms and high water content that makes them comparable to natural tissues. However, these general properties are not sufficient to make any hydrogel suitable for cell attachment and growth which are necessary for their use in tissue regeneration. Besides, the high water content makes the hydrogels mechanically weak. The formation of semi-interpenetrating networks (semi-IPNs) can be used in attempts to enhance physical, mechanical and thermal properties. In this study, semi-IPNs of agarose were prepared with chitosan and alginate, two polyelectrolytes that are positively and negatively charged under physiological conditions, respectively. Zeta potential was used to confirm the formation of charged hydrogels. All hydrogels had ultimate compression strengths in the range of 91–210 Pa where the value for pure agarose was about 103 Pa. Chitosan increased the compressive strength about two folds whereas the alginate had opposite effects. The amount of strongly bound water present in the hydrogels were estimated from TGA and DSC analysis and the highest value was found for alginate-agarose hydrogels as about 15%. The attachment and the migration of L929 fibroblasts were monitored in vitro using the MTS assay and confocal microscopy. The highest cell proliferation and penetration were observed for positively charged chitosan-agarose semi-IPN hydrogels.     

pH-triggered injectable hydrogels prepared from aqueous N-palmitoyl chitosan: In vitro characteristics and in vivo biocompatibility

In-situ forming hydrogels triggered by environmental stimuli have emerged as a promising injectable strategy targeted for various biomedical applications. However, several drawbacks associated with temperature-stimulated hydrogels have been reported. Employing a hydrophobically-modified chitosan (N-palmitoyl chitosan, NPCS), we developed a pH-triggered hydrogel system which showed a rapid nanostructure transformation within a narrow pH range (pH 6.5–7.0). NPCS in an aqueous environment was found to be a shear-thinning fluid and exhibited an instant recovery of its elastic properties after shear thinning, thereby making it an injectable material. Additionally, aqueous NPCS, an associating polyelectrolyte, can be rapidly transformed into hydrogel triggered simply by its environmental pH through a proper balance between charge repulsion and hydrophobic interaction. This in-situ hydrogel system was shown to be nontoxic. Subcutaneous injection of aqueous NPCS (pH 6.5) into a rat model resulted in rapid formation of a massive hydrogel at the location of injection. The implanted hydrogel was found to be degradable and was associated with an initial macrophage response which decreased with time as the degradation proceeded. These results suggested that the developed NPCS hydrogel may be used as an injectable drug/cell delivery system.     

Swelling Response of Radiation Synthesized 2-Hydroxyethylmethacrylate-co-[2-(methacryloyloxy)ethyl] Trimethylammonium Chloride Hydrogels Under Various In Vitro Conditions

High-energy ⁶⁰Co gamma radiation has been used to synthesize 2-hydroxyethylmethacrylate-co-[2-(methacryloyloxy)ethyl]trimethylammonium chloride (HEMA-co-MAETC) polyelectrolyte hydrogels. HEMA-co-MAETC co-polymer gels were characterized and investigated for swelling behaviour in different swelling conditions. Fourier transformed infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) techniques were used to characterize the co-polymer gels. Swelling extent of the gels was found to be a linear function of MAETC content in the gels. The effect of ionic strength, temperature, pH, some solutes of biological importance like glucose, urea, and surfactants such as Triton-X and deoxycholic acid on swelling behavior have been reported. The swelling of gels at higher temperature enhanced the swelling rates but not the swelling extent. HEMA-co-MAETC hydrogel exhibited an excellent responsive characteristic to the ionic strength of the swelling medium. It was found that the swelling of the co-polymer gel at 60°C reduced the swelling–deswelling cycle time by approx. 30% without altering the swelling extent. The gels were also investigated for their swelling in aqueous solutions of anionic dyes, acid blue 25 (AB25), acid blue (AB74) and acid yellow 99 (AY99), and were found to be suitable for dye uptake applications.     

Preparation and characterization of pH-sensitive hydrogel of chitosan/poly(acrylic acid) co-polymer

A pH-sensitive co-polymer hydrogel of chitosan/poly(acrylic acid) (CS/PAAc) was prepared by irradiating the aqueous solution mixture of chitosan and acrylic acid with ⁶⁰Co γ-ray irradiation. The effect of the composition of chitosan and AAc on the properties of the hydrogel, such as swelling ratio and pH-sensitivity, were determined. Fourier Transform Infrared (FT-IR) spectrometry was applied in the attenuated total reflectance (ATR) mode for analyzing the structure change of the hydrogels after the treatment in different pH buffer solutions.     

The effect of pH on the LCST of poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide-co-acrylic acid)

Poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) hydrogels are synthesized by irradiating the aqueous solutions of NIPAAm and NIPAAm/AAc with ⁶⁰Co γ-ray. The effects of pH on the swelling ratio and on the lower critical solution temperature (LCST) are studied by determining the dependence of swelling ratio on temperature in different pH butter solutions. Differential scanning calorimetry (DSC) is applied in determination of the LCST of the hydrogels. Fourier transform infrared (FT-IR) spectrometry is used in the comparison of hydrogels swelled in various pH conditions. As a result, PNIPAAm was found to be a pH-sensitive hydrogel and the LCST of the PNIPAAm and P(NIPAAm-co-AAc) hydrogels are influenced by pH.     

Controlled release of vascular endothelial growth factor by use of collagen hydrogels

In vivo profile of vascular endothelial growth factor (VEGF) release from collagen hydrogels was investigated comparing that of hydrogel degradation while angiogenesis induced by the released VEGF was assessed. Collagen sponges were chemically cross-linked with different amounts of glutaraldehyde for various time periods. When ¹²⁵I-labeled collagen hydrogels incorporating VEGF were subcutaneously implanted into the back subcutis of mice, the hydrogel radioactivity decreased with time, the decrement profile depending on the cross-linking conditions. The radioactivity was retained for longer time periods as the glutaraldehyde concentration and cross-linking time increased. Implantation study of collagen hydrogels incorporating ¹²⁵I-labeled VEGF revealed that the remaining VEGF radioactivity decreased with time and the retention period was prolonged with the decreased hydrogel biodegradation. The slower the hydrogel degradation, the longer the period of VEGF retention. The collagen hydrogel incorporating VEGF induced significant angiogenesis around the implanted hydrogel, in marked contrast to VEGF in the solution form and VEGF-free empty hydrogel. The retention period of angiogenesis became longer with a decrease of the in vivo degradation rate of hydrogels. It is possible that the slower degraded hydrogel achieves a longer period of VEGF release, resulting in prolonged angiogenetic effect. We concluded that in our hydrogel system, biologically active VEGF was released as a result of in vivo degradation of the hydrogel.     

Hydrogel probe for iontophoresis drug delivery to the eye

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm² for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. Iontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.     

Synthesis,Characteristics and Potential Application of Poly(β-Amino Ester Urethane)-Based Multiblock Co-Polymers as an Injectable,Biodegradable and pH/Temperature-Sensitive Hydrogel System

Physical polymeric hydrogels have significant potential for use as injectable depot drug/protein-delivery systems. In this study, a series of novel injectable, biodegradable and pH/temperature-sensitive multiblock co-polymer physical hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PEU) was synthesized by the polyaddition between the isocyanate groups of 1,6-diisocyanato hexamethylene and the hydroxyl groups of PEG and a synthesized monomer BTB (or ETE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized co-polymers were characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and gel-permeation chromatography. Aqueous solutions of the co-polymers showed a sol-to-gel phase transition with increasing pH and a gel-to-sol phase transition with increasing temperature. The gel regions covered the physiological conditions (37°C, pH 7.4) and could be controlled by changing the molecular weight of PEG, PEG/PEU ratio and co-polymer solution concentration. A gel formed rapidly in situ after injecting the co-polymer solution subcutaneously into SD rats and remained for more than 2 weeks in the body. The cytotoxicity tests confirmed the non-cytotoxicity of this co-polymer hydrogel. The controlled in vitro release of the model anticancer drug, doxorubicin, from this hydrogel occurred over a 7-day period. This hydrogel is a potential candidate for biomedical applications and drug/protein-delivery systems.     

A facile method to fabricate thermo- and pH-sensitive hydrogels with good mechanical performance based on poly(ethylene glycol) methyl ether methacrylate and acrylic acid as a potential drug carriers

Abstract

A thermo- and pH-sensitive hydrogel was prepared by a facile free aqueous radical copolymerization of PEGMA and AAc without any crosslinkers for controlled drug delivery. The successful fabrication of hydrogels was confirmed by Fourier transform infrared spectroscopy (FT-IR) and thermo gravimetric analysis (TGA) measurements. The morphological, mechanical and swelling properties of the obtained hydrogels were studied systematically. The results showed that the morphological and mechanical behaviors of the resultant hydrogels were strongly affected by the content of AAc. Moreover, the obtained hydrogels showed an excellent thermo-, pH- and salinity sensitivities. Release profiles of 5-Fu were studied at different pH (gastric pH 1.2 and intestinal pH 7.4) and temperatures (25?°C and 37?°C). The results showed that the release is very low at pH 1.2/37?°C and high at pH 7.4/25?°C. The cytotoxicity of hydrogels to cells was determined by an MTT assay. The result demonstrated that the blank hydrogels had negligible toxicity to cells, whereas the 5-Fu-loaded hydrogels remained high in cytotoxicity for LO2 and HepG-2 cells. Results of the present investigation exemplify the potential of this novel thermo- and pH-sensitive hydrogel for the controlled and targeted delivery of the anti cancer drug 5-Fu.     

In Vitro and In Vivo Biocompatibility of Novel Zwitterionic Poly(Beta Amino)Ester Hydrogels Based on Diacrylate and Glycine for Site‐Specific Controlled Drug Release

New (β‐aminoester) hydrogels (PBAE) based on di(ethylene glycol)diacrylate and glycine are successfully synthesized and characterized for the first time in this work. PBAE macromers are obtained using Michael addition. By changing the diacrylate/amine stoichiometric ratio, but maintaining it >1, samples with different chemical structure containing acrylate end‐groups are obtained. The hydrogels are synthesized from macromers utilizing free radical polymerization. Chemical structure of macromers and hydrogels is confirmed by proton nuclear magnetic resonance, and Fourier transform infra‐red spectroscopy. Swelling and degradation rates in physiological pH range change notably with pH and monomer molar ratio, validating pH sensitivity and zwitterionic behavior, which can be finely tuned by changing any of these parameters. In vitro cytotoxicity and in vivo acute embryotoxicity in zebrafish (Danio rerio) performed to assess the biocompatibility of the novel hydrogel materials and their degradation products reveal that materials are nontoxic and biocompatible. The Cephalexin in vitro drug release study, at pH values 2.20, 5.50, and 7.40, demonstrates pH‐sensitive delivery with the release profiles effectively controlled by pH and the hydrogel composition. PBAE hydrogels exhibit great potential for a variety of biomedical applications, including tissue regeneration and intelligent drug delivery systems.     

Stimuli-sensitivities of hydrogels containing phosphate groups

The effect of an introduction of phosphate groups into hydrogels on their stimuli-sensitivities has been investigated. Several hydrogels containing various phosphate group content were synthesized via solution copolymerization of 2-(methacryloyloxy)ethyl dihydrogen phosphate (Phosmer) and 2-hydroxyethyl methacrylate (HEMA) in the presence of 2,2′-azoisobutyronitrile (AIBN) in methanol at 70°C for 4 h. The content of phosphate groups incorporated into the resulting hydrogels ranged from 1 to 13 mol-%. The swelling ratio of these hydrogels was found to be strongly affected by pH, solvent, temperature and phosphate group content. The polymersolvent interaction parameter χ of the hydrogel was determined from the Flory-Rehner equation, using the swelling ratio and the crosslinking density derived from the compression modulus. Furthermore, χ was divided into its enthalpic (χ_H) and entropic component (χ_S). Using the interaction parameter, the stimuli-sensitivity of the hydrogel is discussed in detail based on thermodynamic aspects.