Synthesis and characterization of novel PEG-tethered PMAA hydrogels based on a PEG macromolecular azo initiator

A new route was proposed to synthesize polyethylene glycol-tethered polymethacrylic acid (viz., PEG-tethered PMAA or PEG-t-PMAA) hydrogels based on a macromolecular azo initiator (MAI), PEG-attached azo initiator. The preparation of the MAI was accomplished by coupling PEG with 2,2-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (AMHP) using 1,1-methylene bis-(4-isocyanato-cyclohexane) (H₁₂MDI) as bridging molecules. The structure and morphologies of the resulting hydrogels were characterized by FTIR and SEM. The pH and ionic strength responses were investigated by swelling measurements, depending on molecular weight (MW) of PEG, molar ratios of isocyanate-terminated PEG to AMHP and mass percentage of the as-prepared MAIs. The PEG-t-PMAA hydrogels synthesized by 100 wt% PEG1000-attached azo initiators and a molar ratio 2 of -NCO-terminated PEG to AMHP exhibit more remarkable pH and ionic strength response than any other hydrogels. The driving force of swelling is believed to be mainly due to the porosity and dissociation balance of PMAA gels as well as gel compositions, while the deswelling behavior may be correlated with the decrease in osmotic pressure caused by the so-called “charge screening effect“ of the cations. The PEG-t-PMAA hydrogels are expected to find specific applications in oral drug delivery and tissue engineering.     

BLUE AND GREEN LIGHT EFFECTS,AND THEIR PHOTOREVERSIBILITY,UPON ZOOSPORE PRODUCTION AND THE SYNCHRONIZED CYCLE IN PROTOSIPHON BOTRYOIDES KLEBS*

Abstract —The synchronized asexual cycle in Protosiphon botryoides Klebs is described. A blue light (430 nm) inhibition of zoospore production can be photoreversed by green light (550 nm). Similarly, a green light (550 nm) stimulation of zoospore production can be photoreversed by blue (430 nm) light. 430 nm light also shortens the period of zoospore motility, and 550 nm light lengthens this period.     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Partitioning of hexavalent chromium in temperature-sensitive,polyelectrolyte hydrogels

Partitioning data for hexavalent chromium (Cr(VI)) are presented for systems where thermally sensitive poly-N-isopropylacrylamide (NIPA)-based hydrogels are in contact with aqueous solutions of potassium dichromate (K₂Cr₂O₇). The poly-NIPA hydrogels contain 0–3% quatemized amine comonomer. Experimental results are given for the effect of gel charge, ionic strength and temperature on the partitioning of Cr(VI) into these NIPA-copolymer gels. At low ionic strength, the partition coefficient increases with the content of quatemized amine. The effect of rising temperature is to increase the partition coefficient. Swelling equilibria in aqueous K₂Cr₂O₇ solutions decrease with ionic strength and, at ionic strengths <0.1 M, are lower compared to swelling in aqueous sodium chloride solutions. Experimental partitioning data as a function of ionic strength and gel charge are compared with predictions based on two theoretical models for mixed electrolyte solutions. Predictions based on the cell model for polyelectrolyte solutions agree best with experimental results. Calculated results are in semi-quantitative agreement with experimental data for the effects of solution ionic strength and gel charge on Cr(VI) partitioning and in qualitative agreement for the effect of temperature.     

Changes in the acid-base properties of hydrogels of metal oxide hydroxides induced by aging in solutions of electrolytes

Changes in the acid-base properties of titanium(IV), zirconium(IV), iron(III), chromium(III), and indium(III) hydrogels of oxide hydroxides induced by aging in sodium chloride and sulfate solutions were studied by the point of zero charge method. On aging in a solution of the sulfate electrolyte the hydrogels loose their basic properties much more rapidly than in the chloride solution. The most changes were observed in the region of high pH of the point of zero charge of the hydrogels. The changes in the acid-base properties can be explained by a decrease in the content of surface OH groups with are displaced by the supporting electrolyte ions, and due to the oxolation of the hydrogels. Published inIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1329–1332, August, 2000.     

Swelling kinetics and release characteristic of crosslinked chitosan: Polyether polymer network (semi-IPN) hydrogels

The aqueous swelling kinetics of a series of crosslinked chitosan (cr-CS) with glutaraldehyde (GA) interpenetrating polyether hydrogels have been studied as functions of pH, the N-deacetylation degree of chitosan, the amount of crosslinking agent, the electrolyte composition in solution, temperature, and gel composition. Based on these results, the swelling mechanism of the hydrogels was discussed. The release profiles of chlorhexidini acetas from the semi-IPN were also investigated. © 1994 John Wiley & Sons, Inc.     

Synthesis,characterization, and evaluation of enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels for colon‐specific drug delivery

The enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels were prepared using 4,4^′‐bis(methacryloylamino)azobenzene (BMAAB) as the crosslinker. It was found that the incorporated N‐isopropylacrylamide (NIPAAm) monomer did not change the enzymatic degradation of hydrogel, but remarkably enhanced the loading of protein drug. The hydrogels exhibited a phase transition temperature between 4°C (refrigerator temperature) and 37°C (human body temperature). Bovine serum albumin (BSA) as a model drug was loaded into the hydrogels by soaking the gels in a pH 7.4 buffer solution at 4°C, where the hydrogel was in a swollen status. The high swelling of hydrogels at 4°C enhanced the loading of BSA (loading capability, ca. 144.5 mg BSA/g gel). The drug was released gradually in the pH 7.4 buffer solution at 37°C, where the hydrogel was in a shrunken state. In contrast, the enzymatic degradation of hydrogels resulted in complete release of BSA in pH 7.4 buffer solution containing the cecal suspension at 37°C (cumulative release: ca. 100 mg BSA/g gel after 4 days). Copyright © 2008 John Wiley & Sons, Ltd.     

Non‐Anticoagulant Heparin Prodrug Loaded Biodegradable and Injectable Thermoresponsive Hydrogels for Enhanced Anti‐Metastasis Therapy

Metastasis is a pathogenic spread of cancer cells from the primary site to surrounding tissues and distant organs, making it one of the primary challenges for effective cancer treatment and the major cause of cancer mortality. Heparin‐based biomaterials exhibit significant inhibition of cancer cell metastasis. In this study, a non‐anticoagulate heparin prodrug is developed for metastasis treatment with a localized treatment system using temperature sensitive, injectable, and biodegradable (poly‐(ε‐caprolactone‐co‐lactide)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone‐co‐lactide) polymeric hydrogel. The drug molecule (heparin) is conjugated with the polymer via esterification, and its sustained release is ensured by hydrolysis and polymeric biodegradation. An aqueous solution of the polymer could be used as an injectable solution at below 25 °C and it achieves gel formation at 37 °C. The anti‐metastasis effect of the hydrogels is investigated both in vitro and in vivo. The results demonstrated that local administration of injectable heparin‐loaded hydrogels effectively promote an inhibitory effect on cancer metastasis.     

Novel nonionic and cationic hydrogels prepared from N-vinylacetamide

Poly(N-vinylacetamide) (polyNVA) hydrogels were prepared by the copolymerization of N-vinylacetamide (NVA) with divinyl compounds such as methylene-bis-acrylamide, methylene-bis-NVA, and butylene-bis-NVA in a high yield. The resulting hydrogels were more stable than polyacrylamide gel and showed quite a high swelling property in a wide range of pH (1–12) and even in a 5M NaCl solution. They showed not only typical characteristics nonionic hydrogels, but also an amphiphilic property and they swelled well in some organic solvents. When the gels were partially hydrolyzed, cationic hydrogels, i.e., crosslinked poly(NVA-co-vinylamine), were collected. The resulting superabsorbent hydrogels absorbed 400 times of water. © 1993 John Wiley & Sons, Inc.     

Phase behaviors of partially ionized hydrogels in aqueous salt solutions: Applicability of the modified double‐lattice model

We investigated the effect of charge densities of the gel network and ionic strength of solution on swelling behaviors of ionized gels. We used the modified double‐lattice model, Flory–Erman's elastic model, and the ideal Donnan theory to describe swelling behaviors of the electrolyte bounded hydrogels. Energy parameters (?/k, δ?/k) were obtained from fitting liquid–liquid equilibria data of the linear poly‐N‐isopropylacrylamide/water system and two adjustable model parameters obtained from a nonelectrolyte hydrogel system. Calculated values agreed with experimental data for the given systems. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 2333–2338, 2002     

Metal adsorption of carboxymethyl cellulose/carboxymethyl chitosan blend hydrogels prepared by Gamma irradiation

Blend hydrogels based on the carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCts) were prepared by γ-irradiation of a high concentrated CMC/CMCts aqueous solution. Properties of the hydrogels, such as gel fraction, swelling ratio, gel strength, and metal adsorption for Pb and Au were investigated. The gel fraction increased with increasing dose, while the swelling ratio decreased with increasing it. The obtained blend hydrogels had high adsorption performance which was controlled by adjusting the composition of CMC/CMCts.     

Photoresponsive Peptide and Polypeptide Systems, 14. Biodegradation of Photocrosslinkable Copolypeptide Hydrogels Containing L‐Ornithine and δ‐7‐Coumaryloxyacetyl‐L‐ornithine Residues

Copoly[Orn/Orn(Cou)] containing δ‐7‐coumaryloxyacetyl‐L ‐ornithine [Orn(Cou)] and L ‐ornithine (Orn) residues was synthesized by the N‐carboxyanhydride method. When aqueous solutions of copoly[Orn/Orn(Cou)] containing 5–10 mol‐% of Orn(Cou) are irradiated, the photoinduced dimerization reaction between coumarin moieties in the side chains proceeds slowly, and after 24 h the solutions become transparent hydrogels. The gels exhibit solvent‐induced reversible expansion and contraction behavior in both water and ethanol. The biodegradation of the hydrogels by proteolytic enzymes and soil filamentous fungi is investigated using photocrosslinked copoly[Orn/Orn(Cou)] gels. The copoly[Orn⁸⁹/Orn(Cou)¹¹] gel is degradable by protease type XXIII, but not by trypsin. In the biochemical oxygen demand test, the order of the microbial biodegradation (%) was Rhizopus sp. (92%) > A. oryzae (38%) > P. caseicolum (18%) > P. citrinum (11%) > Cladosporium sp. (6%). The order for the copoly[Orn⁸⁹/Orn(Cou)¹¹] hydrogel is inverse to that for a polylysine/glutaraldehyde gel. These results suggest that the biodegradabilities of photocrosslinked hydrogels can be controlled by the monomer ratio of Orn, Orn(Cou) and lysine (Lys) in the parent copoly(amino acid)s of the photocrosslinked hydrogels.     

Modified carrageenan. 5. Preparation,swelling behavior,salt‐ and pH‐sensitivity of partially hydrolyzed crosslinked carrageenan‐graft‐polymethacrylamide superabsorbent hydrogel

The polysaccharide, kappa‐carrageenan (κC) was chemically modified to achieve a novel superabsorbent hydrogel via graft copolymerization of methacrylamide (MAM) onto the substrate followed by alkaline hydrolysis. Ammonium persulfate (APS) and N,N′‐methylene bisacrylamide (MBA) were used as a free‐radical initiator and a crosslinker, respectively. The saponification reaction was carried out using sodium hydroxide aqueous solution. Either κC‐g‐PMAM or hydrolyzed κC‐g‐PMAM (PMAM: polymethacrylamide) was characterized by FT‐IR spectroscopy. The effect of grafting variables (i.e. concentration of MBA, MAM, and APS) and alkaline hydrolysis conditions (i.e. NaOH concentration, hydrolysis time and temperature) were systematically optimized to achieve a hydrogel with swelling capacity as high as possible. The swelling capacity of these hydrogels was also measured in various salt solutions. Results indicated that the swelling ratios decreased with an increase in the ionic strength of the salt solutions. This behavior can be attributed to charge screening effect for monovalent cations, as well as ionic crosslinking for multivalent cations. Absorbency of superabsorbing hydrogels was examined in buffer solutions with pH range 1–13. Also, the pH reversibility and on–off switching behavior, at pH values 3.0 and 8.0, makes the synthesized hydrogels good candidates for controlled delivery of bioactive agents. Finally, swelling kinetics in distilled water and various salt solutions was preliminary investigated. Results showed that the swelling in water was faster than in saline solutions. Copyright © 2004 John Wiley & Sons, Ltd.     

Hydrogels of poly(hydroxyethyl methacrylate) and hydroxyethyl methacrylate—glycerol monomethacry-late copolymers

Hydrophilic three-dimensional polymer networks (hydrogels) were prepared from hydroxyethyl methacrylate (HEMA) and the copolymer HEMA and glycerol monomethacrylate (GMMA). The equilibrium water content of the hydrogels in water was investigated as a function of the initial dilution of the polymerization mixture, the type of solvent, and the hydrophilicity of the polymer. The initial dilution was found to have a decisive effect on the swelling or deswelling of hydrogels after the completion of the gel formation. With relatively less hydrophilic hydrogels, there is a critical initial dilution to produce the gel which does not swell or deswell in water after the gel formation. This “isovolumic” initial dilution shifts toward a higher dilution as the hydrophilicity of the hydrogels increases; however, when hydrophilicity of the polymer rises above a certain point, gels always swell in water. Permeability of oxygen through hydrogels was also studied.     

Effect of different electrolytes on the swelling properties of calyx[4]pyrrole-containing polyacrylamide membranes

Calix[4]pyrrole (1) was synthesized and characterized and this macrocycle was incorporated in polyacrylamide gels. The presence of meso-octamethyl-porphyrinogen inside of gel was checked using infrared spectroscopy, differential scanning calorimetry, and swelling studies. The swelling degree of these hydrogels in equilibrium with different electrolytes (NaCl, LiCl, KCl, CaCl₂ and AlCl₃) was measured in a concentration range 0.1-0.5 mol dm⁻³. Although no significant alterations in the swelling degree can be found for the different 1:1 electrolytes, when the cation charge of unsymmetrical electrolytes increases, the gel swells in a significant way. This swelling process is enhanced by the presence of calyx[4]pyrrole. The effect of alkaline hydrolysis of polaycrylamide-based hydrogels was also studied. The hydrolysed hydrogels collapse in the presence of the electrolytes; this behavior is dependent on the hydrolysis degree, electrolyte charge and calyx[4]pyrrole presence and concentration; the latter leads to polyacrylamide with tailor-made properties.     

Hydrogels for in situ encapsulation of biomimetic membrane arrays

Hydrogels are hydrophilic, porous polymer networks that can absorb up to thousands of times their own weight in water. They have many potential applications, one of which is the encapsulation of freestanding black lipid membranes (BLMs) for novel separation technologies or biosensor applications. We investigated gels for in situ encapsulation of multiple BLMs formed across apertures in a hydrophobic ethylene tetrafluoroethylene (ETFE) support. The encapsulation gels consisted of networks of poly(ethylene glycol)‐dimethacrylate or poly(ethylene glycol)‐diacrylate polymerized using either a chemical initiator or a photoinitiator. The hydrogels were studied with regards to volumetric stability, porosity, and water permeability. All hydrogels had pore sizes around 7 nm with volumetric changes >2% upon crosslinking. Photoinitiated hydrogels had a lower hydraulic water permeability compared to chemically initiated hydrogels; however, for all hydrogels the permeability was several‐fold higher than the water permeability of conventional reverse osmosis (RO) membranes. Lifetimes of freestanding BLM arrays in gel precursor solutions were short compared to arrays formed in buffer. However, polymerizing (crosslinking) the gel stabilized the membranes and resulted in BLM arrays that remained intact for days. This is a substantial improvement over lifetimes for freestanding BLM arrays. Optical images of the membranes and single channel activity of incorporated gramicidin ion channels showed that the lipid membranes retained their integrity and functionality after encapsulation with hydrogel. Our results show that hydrogel encapsulation is a potential means to provide stability for biomimetic devices based on functional proteins reconstituted in biomimetic membrane arrays. Copyright © 2010 John Wiley & Sons, Ltd.     

Swelling behaviors of thermoresponsive hydrogels cross-linked with acryloyloxyethylaminopolysuccinimide

Based on a biodegradable cross-linker, acryloyloxyethylaminopolysuccinimide (AEA-PSI), a series of looser cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their water content, swelling/deswelling kinetics, and the morphology of the gels were investigated. The swelling behaviors of AEA-PSI-cross-linked P(NIPAAm/AAc) hydrogels were investigated in Dulbecco’s phosphate-buffered saline (pH = 7.4), in the distilled water, and in the simulated gastric fluids (pH = 1.2), respectively. The water contents of the hydrogels were controlled by the monomer molar ratio of NIPAAm/AAc, swelling media, and the temperature. In the swelling kinetics, all the dried hydrogels exhibited fast swelling behavior, and the swelling ratios were influenced significantly by the amounts of AEA-PSI and AAc content. The deswelling kinetics of the hydrogel were independent of the content of AAc and cross-linker. Lastly, the morphology of the hydrogels was estimated by the field scan electron microscopy.     

Synthesis and characterization of novel biodegradable unsaturated poly(ester amide)/poly(ethylene glycol) diacrylate hydrogels

A series of novel biodegradable hydrogels were designed and synthesized from four types of unsaturated poly(ester amide) (UPEA) and poly(ethylene glycol) diacrylate (PEG‐DA) precursors by UV photocrosslinking. These newly synthesized biodegradable UPEA/PEG‐DA hydrogels were characterized by their gel fraction (G_f), equilibrium swelling ratio (Q_eq), compressive modulus, and interior morphology. The effect of the precursor feed ratio (UPEAs to PEG‐DA) on the properties of the hydrogels was also studied. The incorporation of UPEA polymers into the PEG‐DA hydrogels increased their hydrophobicity, crosslinking density (denser network), and mechanical strength (higher compressive modulus) but reduced Q_eq. When different types of UPEA precursors were coupled with PEG‐DA at the same feed ratio (20 wt %), the resulting hydrogels had similar Q_eq values and porous three‐dimensional interior morphologies but different G_f and compressive modulus values. These differences in the hydrogel properties were correlated to the chemical structures of the UPEA precursors; that is, the different locations of the >C?C< double bonds in individual UPEA segments resulted in their different reactivities toward PEG‐DA to form hydrogels. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3932–3944, 2005     

Adsorption and controlled release of Chlortetracycline HCl by using multifunctional polymeric hydrogels

Adsorption and controlled release of Chlortetracycline HCl to and from multifunctional polymeric materials (HEMA/MAA) hydrogels were investigated. P(HEMA/MAA) hydrogels were synthesized by gamma radiation-induced copolymerization of 2-hydroxyethylmethacrylate (HEMA) and methacrylic acid (MAA) in aqueous solution. The influence of copolymer composition and pH value of the surrounding medium on the type of water diffusion into the glassy polymer were discussed. Drug, Chlortetracycline HCl containing hydrogels, with different drug concentration to polymer ratios, was loaded by direct adsorption method. The influence of MAA content in the gel on the adsorption capacities of hydrogel was studied. Chlortetracycline HCl adsorption capacity of hydrogels was found to increase from 8 to 138 mg Chlortetracycline HCl per gram dry gel with increasing amount of MAA in the gel system and drug concentration. The effect of pH on the releasing behavior of Chlortetracycline HCl from gel matrix was investigated. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MAA content of hydrogel.     

K-型卡拉胶/聚乙烯吡咯烷酮共混水凝胶的辐射合成

采用辐射技术合成了K 型卡拉胶 (KC) /聚乙烯吡咯烷酮 (PVP)共混水凝胶 ,研究了天然高分子KC、单体N 乙烯基吡咯烷酮 (N VP)、交联剂二甲基丙烯酸十四甘醇酯 ( 1 4G) ,辐照剂量以及剂量率等对辐射合成的KC/PVP共混水凝胶性质的影响 .实验发现 ,KC与适当比例的N VP共混后在一定剂量范围内辐照可得到高强度、高溶胀行为的KC/PVP共混水凝胶 ,随着共混凝胶内KC含量的相对增加 ,凝胶强度及溶胀性的能均显著提高 ,但合成该共混凝胶的最佳剂量却相对提前 ;加入 1 4G后降低了KC/PVP共混凝胶辐射合成最佳剂量 ,同时使KC/PVP共混凝胶的强度进一步提高 ;剂量、剂量率对KC/PVP共混凝胶的性质亦有很大的影响 .分析表明 ,KC与N VP共混后 ,在较低剂量下KC的降解被抑制 ,从而获得一种由物理交联的KC和化学交联的PVP形成的互穿网络 (IPN)凝胶