温度、pH及离子强度敏感性聚氨酯水凝胶的合成与性能研究

以甲苯二异氰酸酯(TDI)、聚乙二醇(PEG-6000)、二羟甲基丙酸(DMPA)及三乙撑四胺(TEFA)等为原料,合成了温度、pH、及离子强度敏感性聚氨酯水凝胶(PUHG)。研究了PUHG溶胀率(SR)受温度(T)、pH、离子强度(I)、交联剂用量等因素的影响。结果表明PUHG的溶胀率在20~45℃的范围内随温度的升高而减小,45℃后不再变化;在酸性(pH4)溶液中收缩,在碱性(pH9)溶液中溶胀,表现出良好的pH值敏感性;在一定温度和pH下,随着离子强度的增加PUHG的溶胀率减小。水凝胶溶胀动力学研究表明,PUHG具有良好的溶胀-退胀可逆性。     

Synthesis and characterization of electrically responsive poly(acrylamide)-grafted-chondroitin sulfate hydrogel for transdermal drug delivery application

Abstract

Electrically-responsive transdermal delivery systems (ETDS) were developed utilizing poly(acrylamide)-grafted-chondroitin sulfate (PAAm-g-CS) copolymer. A nitrogen environment based free radical polymerization was used to synthesize electrically responsive PAAm-g-CS copolymer. This PAAm-g-CS hydrogel was used as drug reservoir and cross-linked blend films of CS and poly(vinyl alcohol) as rate controlling membranes (RCM). The drug permeation decreased with increase in the concentration of glutaraldehyde and RCM thickness; while drug permeation was increased with increasing electric stimulus from 2 to 8?mA. Nearly, three-fold increase in flux was observed with the application of electric stimulus. The permeation study under “on–off” electric stimulus suggested that the higher drug permeation was observed under “on” condition of electric stimulus and permeation was decreased when electric stimulus was “off”. The histopathology evaluation confirmed the changes in skin structure when electrical stimulus was applied. Hence, the PAAm-g-CS hydrogel could be a resourceful material for on-demand discharge of medication.     

Superabsorbent hydrogels from poly(aspartic acid) with salt-, temperature- and pH-responsiveness properties

Polyaspartic acid (PAsp) resin was synthesized by polysuccinimide (PSI), through chemical cross-linking using the cross-linking agent (diamine). The effects of reaction variables, such as PSI concentration and terminal pH on the water absorbent capacity have been studied. These phenomena were discussed according to structural parameters, which were confirmed by SEM. Water absorbencies were compared for the hydrogels at terminal pH 8 and 10. The water absorbent capacity enhanced with increasing terminal pH and decreasing PSI concentration. The swelling/deswelling kinetics of the super-absorbent hydrogels was investigated as well. It is found that the hydrogels showed ampholytic and reversible pH-responsiveness properties. The variational water absorbencies were attributed to swelling theory based on the hydrogel physical and chemical structure. The swelling was also extremely sensitive to the temperature, ionic strength and cationic kind. The reversible pH-responsiveness, salt- and temperature-sensitivity of the hydrogels make this intelligentized polymer had wider applications.     

Synthesis and characterization of nanostructured PZT encapsulated PVA–PAA hydrogel

Hydrogel/PZT composite was prepared by encapsulating, Pb(Zr_0.52Ti_0.48)O₃ (PZT) nanoparticles in an electroactive (PVA–PAA) hydrogel. The XRD studies confirmed the presence of pure tetragonal phase in PZT with crystallite size of 13 nm in the composite matrix. PZT nanoparticles were found to be embedded in the micro pores of PVA–PAA hydrogel as indicated by the SEM images. The composite shows three step degradation process in the TG/DTA measurements. Dielectric properties were studied from room temperature to 120 °C within wide frequency range of 100 Hz–600 kHz. At room temperature and intermediate frequency range, the composite shows a high dielectric constant of ~225 to 600 and low dielectric loss of 0.08.     

Synthesis and characterization of poly(HEMA‐MAA) hydrogel carrier for oral delivery of insulin

Poly(HEMA‐MAA) hydrogel particles were synthesized by redox free‐radical polymerization using 2‐hydroxyethylmethacrylate, different concentration of methacrylic acid as monomer, ethyleneglycol dimethacrylate as crosslinking agent, and APS/TEMED as free‐radical initiator. Fourier transform infrared spectrum of poly(HEMA‐MAA) hydrogels showed intense absorption peak of carbonyl group at ～ 1700 cm^?1 due to carboxylic acid groups of MAA, peak at ～ 2960 cm^?1 due to CH stretching and vinylic peak at 1700 cm^?1 independent of MAA concentration. Highest swelling percentage 587% was observed in case of poly(HEMA‐MAA) hydrogel synthesized using 30% of MAA while lowest swelling percentage 413% was observed in hydrogel synthesized 10% of MAA at basic pH (8.0). Scanning electron micrograph of copolymeric particles showed the irregular shape of poly(HEMA‐MAA) particles with conglomeration with each due to ionization of carboxylic groups. Insulin was radiolabeled using technetium‐99m radionuclide and the radiolabeling efficiency was found to be 99%. Poly(HEMA‐MAA) hydrogel having 60% of MAA showed the highest insulin loading efficiency of 68% while lowest 37% was observed in case of 10% MAA hydrogel. Insulin release studies showed only 35–65% of insulin was released into the medium from particles at pH 2.5 in 60 min, while insulin release was significantly higher at pH 7.4. Hypoglycemic effect of the 60 and 80 I.U./kg insulin dose loaded in poly(HEMA‐MAA) copolymeric particles were carried out in fasted diabetic rats and highest decrease in blood glucose level from 506 mg/dL to 170 mg/dL was observed within first 3 h. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Synthesis and Characterization of Temperature-Sensitive Poly(N-isopropylacryamide) Hydrogel with Comonomer and Semi-IPN material

A series of temperature and pH sensitive hydrogels were synthesized using N-isopropylacrylamide (NIPAAm) as main monomer, sodium alginate (SA) as semi-IPN material, ethyl acrylate (EA) and acrylic acid (AA) as comonomer, and N-maleyl chitosan (N-MACH) as cross-linker. The temperature and pH sensitive behavior, swelling/deswelling kinetics of the hydrogels were investigated. And the mechanism of the phase transition was summed up. Sodium alginate/Poly(N-isopropylacryamide) semi-interpenetrating polymer network (SA/PNIPAAm semi-IPN) hydrogels exhibited a lower critical solution temperature (LCST) at about 32 °C with no significant deviation from the conventional PNIPAAm hydrogels. Poly(N-isopropylacryamide-co-ethyl acrylate) (P(NIPAAm-co-EA)) hydrogels exhibited LCST at 29–31°C, increasing the amount of EA in the hydrogel gradually decreased the LCST. Poly(N-isopropylacryamide-co-acrylic acid) [P(NIPAAm-co-AA)] hydrogels exhibited LCST at 34–39°C, with decreasing NIPAAm/AA from 96/4 to 92/8 and 90/10, the LCST increased from 34°C to 37°C and 39°C. In the swelling/deswelling kinetics, all the dried hydrogels exhibited fast swelling/deswelling behavior, which might be attributed to macroporous structures of the hydrogels.     

A self-healing and conductive ionic hydrogel based on polysaccharides for flexible sensors

In this study, we proposed a self-healing conductive hydrogel based on polysaccharides and Li⁺ to serve as flexible sensors. At first, the oxidized sodium alginate(OSA) was obtained through the oxidation reaction of sodium alginate(SA). Then OSA, carboxymethyl chitosan(CMC), and agarose(AGO) were dissolved in Li Cl solution, respectively. Finally, the hydrogel was obtained through heating, mixing, and cooling processes. Because of the Schiff base structure and hydrogen bonding, the hy...     

Synthesis and characterization of pH- and temperature-sensitive hydrogel of N-isopropylacrylamide/cyclodextrin based copolymer

A reactive β-Cyclodextrin (β-CD) based monomer carrying vinyl carboxylic acid functional groups was synthesized via reaction of β-CD with maleic anhydride (MAH) in N,N-dimethylformamide (DMF) at 80 °C. By copolymerization of the monomer with N-isopropylacrylamide (NIPA), a novel hydrogel, poly(NIPA-co-MAH-β-CD) with pH and temperature sensitivities plus molecular inclusion function, was obtained using free radical polymerization in aqueous solution. The hydrogel's composition was determined by element analysis and infrared spectroscopy. Equilibrium swelling ratio (ESR) of hydrogels was tested under different environment of pH, temperature and ionic strength. The results indicated that ESR of hydrogels presents marked variations following the change of experimental conditions used.     

pH值／电场双重敏感水凝胶的合成及性能测定

从分子设计的角度出发,合成了pH值／电场双重敏感水凝胶,测试了其系列理化性能,包括密度、分子质量、交联密度、固定电荷密度、离解pH值及力学性能等,探讨了离子强度、pH值、电场等因素对水凝胶溶胀率的影响机理及影响趋势。     

一种新型聚天冬氨酸水凝胶的制备及其药物缓释性能研究

介绍了一种新型羟化聚天冬氨酸-乙基纤维素(PASP-EC)互穿网络水凝胶的制备,研究了交联剂用量、乙醇胺用量及乙基纤维素(EC)用量对水凝胶溶胀性能的影响;同时,进行了水凝胶的pH敏感性测试,并以5-Fu为药物模型,研究其在肠液中(pH=7.4)的药物控释性能。实验结果表明,当己二胺、乙醇胺、EC的用量分别是聚琥珀酰亚胺(PSI)用量的3%、20%、30%时,水凝胶的溶胀性能最佳,达到290倍;且随着乙醇胺用量的增加,水凝胶在50%乙醇中的溶胀性能提高。pH敏感实验表明,羟化PASP-EC水凝胶具有pH敏感性。羟化PASP-EC水凝胶对5-Fu具有缓释效果,随着EC用量增加,缓释效果越明显。     

新型咪唑型手性离子液体的合成与表征

以天然手性源L-脯氨酸为原料,利用离子液体特殊的结构可调性质,将手性引入到离子液体结构中,经多步中间体合成了水溶性、室温下呈液相的新型咪唑型手性离于液体,总产率80%,并对各中间体及目标产物进行了LC-MS、13CNMR和1HNMR和一些物理性质的测定.     

Synthesis and characterization of block-copolymer surfactants with specific interactions with associative thickeners

It has been theorized that, in order to get some positive interaction with the associative thickeners, the surfactants should have, at the end of the hydrophilic sequence, a short hydrophobic group. On the other hand, in order to control the hydrophilic lipophilic balance (HLB), it is wise to use well controlled polymerization procedures to build the block-copolymer. Then, the safer and simplest way to reach such goal is to use the ring-opening living anionic polymerization of butylene oxide (hydrophobic sequence) and then ethylene oxide (hydrophilic sequence); this living block-copolymer is then killed using an alkyl or aryl chloride (or bromide). However, because such surfactants include at the end of the hydrophilic sequence a hydrophobic group, they tend to adopt, when adsorbed onto hydrophobic latex particles, a back-folded conformation. In order to get for them an extended conformation, the hydrophilic sequence should have charges able to repel each other. This was achieved upon preparing block-copolymers of acrylic acid and butylacrylate, using a controlled radical polymerization with reversible addition fragmentation transfer (RAFT) agents, starting with the poly(acrylic acid) (PAA) sequence. Then, the radical fragment coming from the RAFT agent is at the end of the PAA sequence. A few rheological data actually confirm the interest of the concept.     

Synthesis,characterization, and properties of novel hydrophobically associating fluorinated copolymers for DNA delivery

Novel fluorinated associative copolymers poly(ethylene glycol)-b-poly(2-(perfluorohexyl)ethyl methacrylate (PFHEMA)-co-3-[N-(2-methacroyloylethyl)-N,N-dimethylammonio]-propane sulfonate (DMAPS)) (PEG-b-PPFHEMA/PDMAPS) were prepared as a type of non-viral gene vector. The series of PEG-b-PFHEMA/DMAPS with different molecular weights and compositions were characterized by gel permeation chromatography–multi-angle light scattering, ¹H NMR, ¹⁹F NMR, and elemental analysis. The interactions of the copolymers with calf thymus DNA and the morphologies of the resulting complexes were studied by fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. In addition, the DNA–polymer interaction, as determined by the gel retardation assay, and the low cytotoxicity of PEG-b-PPFHEMA/PDMAPS demonstrated that these copolymers have good DNA binding capacity and potential for high performance in the practical application of DNA delivery.     

Synthesis of superabsorbent hydrogel nanocomposites for use as hemostatic agent

Uncontrolled hemorrhage continues to be the major cause of death in trauma. In this study, the authors prepared hydrogel nanocomposites (HNCs) using three different nanoparticles, SiO₂, natural clinoptilolite (nC), and Ca²⁺-modified clinoptilolite (mC). Fast-swelling superabsorbent hydrogel was used as a matrix of NCs. The hydrogel and HNCs were characterized by FTIR, XRD, FE-SEM, and TGA. The hemocompatibility of HNCs was evaluated by hemolysis test and blood cells function. HNC formed a physical barrier by dehydrating the injury site and concentrating clotting factors. Additionally, highly charged nanoparticles, promoted local hemostasis by activating the intrinsic pathway of the blood coagulation cascade.     

Synthesis and characterization of a dually crosslinked heparin-conjugated HA hydrogel for BMP-2 sustained delivery

A dually crosslinked heparin-conjugated hyaluronan hydrogel (DCH) was synthesized for reinforcement and sustainably delivering growth factors in tissue engineering. Heparin-conjugated hyaluronan microgels after glycidyl methacrylation as reinforcing phase crosslinked with glycidyl-methacrylated hyaluronan as matrix phase by ultraviolet radiation. The morphology, water swelling ratio, rheological property, degradation, bone morphogenetic protein-2 (BMP-2) loading and delivery, and cytotoxicity were characterized. Increasing heparin content enhanced the loading and sustainable delivery of BMP-2, but partly attenuated the mechanical property of DCH that presented a much higher elastic modulus than bulk gel. The incorporation of heparin and dually crosslinked network was harmless to the good cytocompatibility of hyaluronan hydrogel.     

Design of microcapsules with hydrogel as a membrane component and their preparation by a spouted bed

This paper describes particulate design and preparation to control drug release thermosensitively or in a delayed mode from microcapsules (MCs) that were prepared by coating with a membrane incorporating hydrogel as a particulate or chemical component. The particulate preparation was carried out by a spouted bed coating process. The microcapsules releasing drug with a positive thermosensitivity were prepared by dispersing the newly developed latex particles in the ethylcellulose matrix membrane. The latex particles were synthesized so as to have a thermoinsensitive core and a thermosensitive poly(N-isopropylacrylamide) hydrogel shell. Poly(N-isopropylacrylamide) with a lower critical solution temperature (LCST) at 32 °C in water shrank at higher temperatures and highly swelled at lower temperatures than LCST, leading to so-called positively thermosensitive release. On the other hand, when the acrylic ter-polymer of latex particles has a hydrophilic component, 2-hydroxyethyl methacrylate, the water uptake rate of microcapsules could be controlled by its content in the ter-polymer and membrane thickness. The release was characterized by a delayed mode; then the lag time was controlled by the 2-hydroxyethyl methacrylate content and the membrane thickness. This content was also related to the mechanical flexibility of membrane that was critical in the release rate control after the release of drug starts.     

Synthesis and characterization of a novel soil stabilizer based on biodegradable poly(aspartic acid) hydrogel

A novel soil stabilizer based on poly-amino acid - polyaspartic acid (PASP) and its copolymer which modified by xanthan gum (XG) was studied to increase soil particle compressive strength and resistance to wind erosion. Due to its unique property, the stabilizer aggregated individual soil particles and formed crust. The sample compressive strength increased from 0.175 to 0.612 MPa and the wind erosion modulus reduced from 22.43 to 10.56 g·m⁻²·min⁻¹ after the 1% PASP hydrogel was applied by 1.67 Lm⁻² (1 cm of crust). The soil water content was higher than the control due to the polymer’s excellent water-retaining property. The polymer had no negative influence on seed germination and growth. The biodegradability experiment showed that PASP was easy to biodegrade and therefore it was safe to apply in the field. This work was presented at 13 ^th YABEC symposium held at Seoul, Korea, October 20–22, 2007.     

Synthesis and characterization of photo-crosslinkable hydrogel membranes based on modified chitosan

In order to develop a non toxic and biocompatible hydrogel system with potential ability in biotechnology, modified photo-crosslinkable hydrogel membranes based on chitosan were prepared. Using an EDC/NHS conjugation method, chitosan was chemically modified to incorporate a photosensitive α-cyano-4-hydroxycinnamic acid moiety with various degrees of substitutions. Fourier transform infrared spectra (FTIR), proton nuclear magnetic resonance (¹H NMR) and ultraviolet-visible light spectra (UV-vis) were used for structural characterization of modified chitosan, The obtained membranes were crosslinked by irradiation in the ultraviolet region, where the photosensitive monomers showed maximum sensitivity. The prepared photo-crosslinked hydrogel membranes were investigated by thermal gravimetric analysis (TGA) and wide angle X-ray diffraction (WAXD). The swelling behaviors were investigated in terms of pH, time of swelling, and degree of substitution. Also, mechanical properties of the different photo-crosslinked hydrogel membranes were studied in both dry and wet conditions.     

Amphiphilic gradient poly(styrene-co-acrylic acid) copolymer prepared via nitroxide-mediated solution polymerization. Synthesis, characterization in aqueous solution and evaluation as emulsion polymerization stabilizer

A well-defined, amphiphilic poly(styrene-co-acrylic acid) copolymer was synthesized in a single step by nitroxide-mediated controlled free-radical copolymerization of styrene and acrylic acid, without protection of the acid groups: M_n=6500 g mol⁻¹, M_w/M_n=1.5 and a composition of F_AA=0.70±0.03 in acrylic acid. In addition to the good control over molar mass and molar mass distribution, the copolymer exhibited a narrow composition distribution with a slight gradient. Such copolymer was an efficient stabilizer for the emulsion polymerizations of styrene and of mixtures of methyl methacrylate and n-butyl acrylate, until 45 wt% solids. A low amount (typically 3-4 wt% based on the monomer(s)) was needed for a good stabilization. This is approximately a decade lower than the required amount of random, amphiphilic copolymers prepared via conventional free-radical polymerization. The performances were, however, below those of analogous diblock copolymers, but the great advantage is the very easy synthetic procedure.     

Thermo- and pH-responsive HPC-g-AA/AA hydrogels for controlled drug delivery applications

This paper describes smart hydrogels composed of pH-sensitive poly(acrylic acid) (PAA) and biodegradable temperature-sensitive hydroxypropylcellulose-g-acrylic acid (HPC-g-AA) for controlled drug delivery applications. In a pH-responsive manner, the hydrogels with the higher HPC-g-AA content resulted in the lower equilibrium swelling. Although temperature had little influence on the swelling of the hydrogels, optical transmittance of the hydrogels was changed as a function of temperature, which reflecting that the HPC parts of hydrogel became hydrophobic at temperature above the lower critical solution temperature (LCST). Scanning electron microscopic analysis revealed that the pore size and the morphology of the hydrogels could be controlled by changing the composition of AA and the crosslinking density. Using BSA as a model drug, in vitro drug release experiment was carried out in artificial gastric juice (pH = 1.2) for the first 2 h and then in artificial intestinal liquid (pH = 6.8) for the subsequent 6 h. The release profiles indicated that both HPC-g-AA and AA contents played important roles in the drug release behaviors. The temperature- and pH-responsive HPC-g-AA/AA hydrogels might be exploited for wide applications in controlled drug delivery.