通过麦克加成反应形成的三臂聚乙二醇丙烯酸酯可注射水凝胶的制备与表征

通过麦克加成反应在磷酸盐缓冲溶液中制备出一种基于三臂聚乙二醇丙烯酸酯的能快速固化的可注射水凝胶.采用倒置法测定了体系的凝胶化时间.通过红外,DMA,溶胀,降解等一系列测试,研究了该水凝胶的结构和物理化学性能.观察到通过控制前体溶液的浓度,可以控制凝胶的成胶时间和所形成凝胶的溶涨率.同时表明该水凝胶具备可注射性和可降解性.细胞毒性评价显示,该水凝胶浸提液无毒性,符合生物材料的安全评价标准.由于麦克加成反应可在人体生理条件(pH7.4,37℃)下快速进行,并且不需要任何引发剂、催化剂和有机溶剂,因此该反应非常适合应用于生物医用材料领域.     

Development of Injectable Biodegradable Multi-Arms PEG-Based Hydrogels: Swelling and Degradation Investigations

Summary : Injectable biodegradable hydrogels have been developed to determine the efficacy of biomaterials for the treatment of periodontitis through control delivery of bone-healing bioactives. The hydrogels were prepared from the PEG-ylated macromer of Boltorn™ H20 (BH20) and an acrylated triblock copolymer of polylactide-polyethylene glycol (2k)-polylactide (PLA) in various molar ratios using ammonium persulfate and sodium ascorbate as a free radical initiating system. Preliminary investigations involving the synthesis of PLA hydrogels with different PLLA block lengths were studied in order to determine the swelling ratios and degradation rates of the biodegradable component of the hydrogels prior to copolymerization with BH20. The swelling and degradation studies of PLA with PEG diacrylate (FW 700) hydrogels were established in phosphate buffered saline (PBS) at 37 °C, pH 7.4 and in water (pH ∼5.5). They have been shown to have low swelling ratios (Q_max = 4.4 to 3.6) and degradation times of 20–30 days. The swelling and degradation parameters were found to be dependent on the molar ratio of the PEG diacrylate to PLA in the copolymer.     

Preparation and characterization of pH- and temperature-responsive semi-IPN hydrogels of carboxymethyl chitosan with poly (<Emphasis Type="Italic">N</Emphasis>-isopropyl acrylamide) crosslinked by clay

A new kind of pH- and temperature-responsive semi-interpenetrating polymer network hydrogel based on linear carboxymethylchitosan (CMCS) and poly (N-isopropylacrylamide) (PNIPA) crosslinked by inorganic clay was prepared. The pH-and temperature-responsive behaviors, the deswelling kinetics, and the mechanical properties of the hydrogel were investigated. The hydrogels exhibited a volume phase transition temperature around 33 °C with no significant deviation from the conventional PNIPA hydrogels. The results of the influence of pH value on the swelling behaviors showed that the minimum swelling ratios of the hydrogels appeared near the isoelectric point (IEP) of CMCS, and when pH deviated from the IEP, the hydrogels behaved as polycations or polyanions. The novel hydrogels had much higher response rate than the conventional CMCS/PNIPA hydrogels. Moreover, the semi-IPN hydrogels crosslinked by clay could be elongated to more than 800% and the elongation could be recovered almost completely and instantaneously.     

Application Properties of Stimuli-Responsive Polyglycerol Hydrogels

Transient state swelling behavior and swelling kinetics of novel stimuli-responsive polyglycerol hydrogels were studied at 293, 310 and 333 K. Depending on temperature, Fickian or anomalous diffusion behavior was observed. Mechanical properties of the hydrogels in the swollen and dry states were investigated and the average molecular weight between crosslinks was calculated. To assess the potential for biodegradation of hydrogels, initial swelling behavior in phosphate buffered saline (PBS) solution and mass loss profiles as a function of degradation time were investigated over a period of 30 days. All swelling behavior, mechanical properties and degradations were clearly affected by the degree of cross-linking. The hydrophilicity and biodegradability of polyglycerol hydrogels make them suitable for pharmaceutical, biomedical and biotechnological applications. They could potentially serve as a substitute for common fossil-based hydrogels such as poly(ethylene glycol) and poly(vinyl alcohol) hydrogels.     

Synthesis and characterization of novel thermoresponsive‐co‐biodegradable hydrogels composed of N‐isopropylacrylamide,poly(L‐lactic acid), and dextran

A series of novel multifunctional hydrogels that combined the merits of both thermoresponsive and biodegradable polymeric materials were designed, synthesized, and characterized. The hydrogels were copolymeric networks composed of N‐isopropylacrylamide (NIPAAM) as a thermoresponsive component, poly(L‐lactic acid) (PLLA) as a hydrolytically degradable and hydrophobic component, and dextran as an enzymatically degradable and hydrophilic component. The chemical structures of the hydrogels were characterized by an attenuated total reflection–Fourier transform infrared spectroscopy (ATR–FTIR) technique. The hydrogels were thermoresponsive, showing a lower critical solution temperature (LCST) at approximately 32 °C, and their swelling properties strongly depended on temperature changes, the balance of the hydrophilic/hydrophobic components, and the degradation of the PLLA component. The degradation of the hydrogels caused by hydrolytic cleavage of ester bonds in the PLLA component was faster at 25 °C below the LCST than at 37 °C above the LCST, determined by the ATR–FTIR technique. Due to their multifunctional properties, the designed hydrogels show great potential for biomedical applications, including drug delivery and tissue engineering. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5054–5066, 2004     

α-环糊精准轮烷/N-异丙基丙烯酰胺交联共聚温敏型超分子结构水凝胶的制备与表征

采用一锅法合成了甲基丙烯酰基封端的聚乳酸-聚乙二醇-聚孔酸(PLA-PEG-PLA)三嵌段大分子单体,然后再通过与α-环糊精进行超分子自组装,得到聚准轮烷.将制备的聚准轮烷悬浮在N-异丙基丙烯酰胺水溶液中,再加入适量的光引发剂,在紫外光的照射下,溶液快速固化,得到了具有超分子结构的温敏型凝胶体.采用FTIR、TG、XRD等分析手段对所得聚准轮烷及其水凝胶进行了表征.     

温度敏感聚(N-异丙基丙烯酰胺)/聚(乙烯醇)水凝胶的制备及性能研究

聚 (N -异丙基丙烯酰胺 ) (PNIPA)水凝胶具有温度敏感性 ,其在 33℃左右有一个相转变温度或较低临界溶解温度 (L CST) [1,2 ] .当外界温度低于 LCST时 ,PNIPA水凝胶吸水溶胀 ;而当外界温度高于L CST时 ,PNIPA水凝胶剧烈收缩失水 ,发生相分离 .这种相分离特性应用于药物的控制释放 [3] .固定化酶[4 ] 和循环吸收剂 [5] 等领域 .然而 ,通常的 PNIPA水凝胶是通过化学键交联而成的三维网络聚合物 ,很难发生解体或进行生物降解 ,其在某些特定场合 (如药物的体内释放等 )受到一定限制 .聚乙烯醇 (PVA)的亲水性和生物相容性较好 ,是…     

Organic–inorganic hybrid hydrogels involving poly(N‐isopropylacrylamide) and polyhedral oligomeric silsesquioxane: Preparation and rapid thermoresponsive properties

3‐Acryloxypropylhepta(3,3,3‐trifluoropropyl) polyhedral oligomeric silsesquioxane (POSS) was synthesized and used as a modifier to improve the thermal response rates of poly(N‐isopropylacrylamide) (PNIPAM) hydrogel. The radical copolymerization among N‐isopropylacrylamide (NIPAM), the POSS macromer and N,N′‐methylenebisacrylamide was performed to prepare the POSS‐containing PNIPAM cross‐linked networks. Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) showed that the POSS‐containing PNIPAM networks displayed the enhanced glass transition temperatures (T_g's) and improved thermal stability when compared with plain PNIPAM network. The POSS‐containing PNIPAM hydrogels exhibited temperature‐responsive behavior as the plain PNIPAM hydrogels. It is noted that with the moderate contents of POSS, the POSS‐containing PNIPAM hydrogels displayed much faster response rates in terms of swelling, deswelling, and re‐swelling experiments than plain PNIPAM hydrogel. The improved thermoresponsive properties of hydrogels have been interpreted on the basis of the formation of the specific microphase‐separated morphology in the hydrogels, that is, the POSS structural units in the hybrid hydrogels were self‐assembled into the highly hydrophobic nanodomains, which behave as the microporogens and promote the contact of PNIPAM chains and water. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 504–516, 2009     

Poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) networks with tailored water sorption

A poly(l-lactide) diol was obtained through ring opening polymerization of l-lactide, using 1,6 hexanediol and tin(II) 2 ethylhexanoate as a catalyst. In the second step, the poly(l-lactide) macromer (mLA) was obtained by the reaction of poly(l-lactide) diol with methacrylic anhydride. The effective incorporation of the polymerizable end groups was assessed by Fourier transform infrared spectroscopy and nuclear magnetic resonance (¹H NMR). Besides, poly(l-lactide) networks (pmLA) were prepared by photopolymerization of mLA. Further, the macromer was copolymerized with 2-hydroxyethyl acrylate seeking to tailor the hydrophilicity of the system. A set of hydrophilic copolymer networks were obtained. The phase microstructure of the new system and the network architecture was investigated by differential scanning calorimetry, infrared spectroscopy, dynamic mechanical spectroscopy, thermogravimetry, and water sorption studies.     

Synthesis and characterization of κ‐carrageenan/poly(N,N‐diethylacrylamide) semi‐interpenetrating polymer network hydrogels with rapid response to temperature

In this study, a novel classical thermo‐ and salt‐sensitive semi‐interpenetrating polymer network (semi‐IPN) hydrogel composed of poly(N,N‐diethylacrylamide) (PDEAm) and κ‐carrageenan (KC) was synthesized by free radical polymerization. The structure of the hydrogels was studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). FTIR and SEM revealed that the semi‐IPN hydrogels possessed the structure of H‐bonds and larger number of pores in the network. Compared to the PDEAm hydrogel, the prepared semi‐IPN hydrogels exhibited a much faster response rate to temperature changes and had larger equilibrium swelling ratios at temperatures below the lower critical solution temperature (LCST). The salt‐sensitive behavior of the semi‐IPN hydrogels was dependent on the content of KC. In addition, during the reswelling process, semi‐IPN hydrogels showed a non‐sigmoidal swelling pattern. Copyright © 2008 John Wiley & Sons, Ltd.     

P(AMPS-co-BMA)水凝胶的电场敏感性及电刺激响应机理

以离子型单体2-丙烯酰胺-2-甲基丙磺酸(AMPS)及非离子型单体甲基丙烯酸丁酯为原料, 偶氮二异丁腈为引发剂, N,N′-亚甲基双丙烯酰胺为交联剂, N,N-二甲基甲酰胺为溶剂, 通过自由基聚合合成了一系列聚离子浓度不同的聚(2-丙烯酰胺-2-甲基丙磺酸-co-甲基丙烯酸丁酯)电场敏感性水凝胶. 研究了其在去离子水及NaCl溶液中的溶胀行为. 结果表明, 该水凝胶在去离子水中的平衡溶胀度在236.4~298.5之间, 其溶胀速率随着AMPS用量的增加而增加; 并且随着凝胶内部聚离子浓度的增加, 凝胶在NaCl溶液中的消溶胀速率及消溶胀度逐渐减小. 凝胶的电刺激响应性能研究结果表明, 在电场存在下, 凝胶在NaCl溶液中的溶胀行为与凝胶内部聚离子浓度和溶液中NaCl浓度的相对大小有关, 当凝胶内部聚离子浓度大于溶液中NaCl浓度时, 凝胶溶胀, 反之则凝胶消溶胀; 而且, 凝胶在电场作用下的偏转行为同样与凝胶内部聚离子浓度和溶液中NaCl浓度的相对大小有关, 当凝胶内部聚离子浓度大于溶液中NaCl浓度时, 偏向阴极, 反之则凝胶偏向阳极. 另外, 在电场存在下, 凝胶在NaCl溶液中的电偏转速度与环境温度密切相关.     

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.     

Biodegradable thermo‐ and pH‐responsive hydrogels for oral drug delivery

In this article, novel smart hydrogels based on biodegradable pH sensitive poly(L ‐glutamic acid‐g‐2‐hydroxylethyl methacrylate) (PGH) chains and temperature‐sensitive hydroxypropylcellulose‐g‐acrylic acid (HPC‐g‐AA) segments were designed and synthesized. The influence of pH and temperature on the equilibrium swelling ratios of the hydrogels was discussed. The optical transmittance of the hydrogels was also changed as a function of temperature, which reflecting that the HPC‐g‐AA part of the hydrogels became hydrophobic at the temperature above the lower critical solution temperature (LCST). At the same time, the LCST of the hydrogels had a visible pH‐dependent behavior. Scanning electron microscopic analysis revealed the morphology of the hydrogels before and after enzymatic degradation. The biodegradation rate of the hydrogels was directly related to the PGH content and the pH value. The in vitro release of bovine serum albumin from the hydrogels were investigated. The release profiles indicated that both the HPC‐g‐AA and PGH contents played important roles in the drug release behaviors. These results show that the smart hydrogels seem to be of great promise in pH–temperature oral drug delivery systems. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of poly(ethylene glycol)‐based hydrogels and their swelling/shrinking response to molecular recognition

To synthesize the novel molecular‐ and pH‐stimulus‐responsive hydrogel, we prepared poly(ethylene glycol)‐based hydrogel containing ionic groups. We evaluated the fundamental swelling/shrinking properties of the hydrogels synthesized by various conditions. Decreasing the molecular weight of a crosslinker provided the increasing of the equilibrium swelling ratio. Also, the equilibrium swelling ratio was changed by the introduction of functional ionic monomers and its compositions. Furthermore, the swelling/shrinking behaviors of the hydrogels were affected by the environmental condition of aqueous solution, in fact the hydrogels were considerably shrunk (to one‐fifth volume) using a di‐ionic solute in the aqueous solution through the ionic interactions between the hydrogel and the solutes. Additionally, the specific shrinking to diamine compounds was also observed in response to pH change. These results clearly show the swelling/shrinking responsibility of the hydrogels toward the molecular recognitions and its pH conditions. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3153–3158     

Synthesis and thermal properties of a novel lactose‐containing poly(N‐isopropylacrylamide‐co‐acrylamidolactamine) hydrogel

An improved, simple, and efficient method for the synthesis of lactose‐containing monomer acrylamidolactamine (LAM) has been reported. Free radical copolymerization of this monomer with N‐isopropylacrylamide (NIPAM) in the presence of the crosslinking reagent N,N′‐methylenebisacrylamide (BisA) (1.2 mol %) proceeded smoothly in an aqueous solution using potassium persulfate (KPS) and N,N,N′,N′‐tetramethylethylenediamine (TMEDA) as the initiating system and gave transparent hydrogels. Reactivity ratios were estimated from copolymerization reactions carried out in solution without BisA crosslinker and at low conversion, by using both linearization and nonlinearization methods. They were found to be r_LAM = 0.75 and r_NIPAM = 1.22. The swelling behavior of the hydrogels was studied by immersion of the hydrogels in deionized water at different temperatures. Equilibrium water uptake was increased when the LAM content was higher than 47 mol %, and reached ≈ 44‐fold with 100 mol % LAM at room temperature. Depending on the composition, the gels showed sharp swelling transitions with small changes in temperature. Differential scanning calorimetry (DSC) was used to characterize the swelling transition and the organization of water in the copolymer hydrogels. The amounts of freezable water in these hydrogels ranged from 81 to 89%, and was not correlated to the content of the sugar monomer. These gels have potential applications as biocompatible materials. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1393–1402, 1999     

基于多巴胺的黏合水凝胶的制备及表征

以1-(3-二甲氨基丙基)-3-乙基碳二亚胺/N-羟基琥珀酰亚胺(EDC/NHS)为催化剂, 将多巴胺通过酰胺化反应连接到氧化海藻酸钠上, 制得含邻苯二酚结构的氧化海藻酸钠(COA), 将COA与胶原(COL)复合, 制得具有黏合性能的COA-COL水凝胶, 通过紫外-可见光谱(UV-Vis)、 傅里叶变换红外光谱(FTIR)和核磁共振波谱(¹H NMR)方法表征了COA的结构, 用扫描电子显微镜、 体外膨胀降解、 万能电子拉力机和噻唑蓝(MTT)法分别表征了COA-COL水凝胶的形貌结构、 平衡溶胀率、 降解率、 黏合强度和细胞毒性. 研究结果表明, 多巴胺已引入到氧化海藻酸钠上, 取代度分别为12.5%, 18%和22%; COA-COL水凝胶的内部形成了典型的海绵体多孔网状结构, 平衡溶胀率随着多巴胺取代度的提高先减小后增大, 降解率随着取代度的提高依次减小, COA-COL水凝胶的黏合强度从未经多巴胺改性时的(20.43±4.21) kPa提高到多巴胺取代度为22%时的(29.91±6.10) kPa, 而且具有良好的生物相容性.     

含聚1,3-二氧戊环链段可降解pH敏感性水凝胶的合成与表征

制备了含聚 1,3 二氧戊环链段具有pH敏感性的可解体聚合物凝胶网络 ,网络可在水中及有机溶剂中溶胀 ,且由聚 1,3 二氧戊环构成的水凝胶成分可以在酸性介质中降解 ,使网络解体 .利用红外光谱、色 质联谱等分析手段对聚合物凝胶网络进行了表征 .通过对降解产物的分析 ,一方面证实了降解现象的存在 ,另一方面证实了聚合反应机理     

Biodegradable water absorbent synthesized from bacterial poly(amino acid)s

Biodegradable hydrogels prepared by gamma-irradiation from microbial poly(amino acid)s have been studied. pH-Sensitive hydrogels were prepared by the gamma-irradiation of poly(gamma-glutamic acid) (PGA) produced by Bacillus subtilis and poly(epsilon-lysine) (PL) produced by Streptomyces albulus in aqueous solutions. When the gamma-irradiation dose was 19 kGy or more, and the concentration of PGA in water was 2 wt.-% or more, transparent hydrogels could be produced. For the 19 kGy dose, the produced hydrogel was very weak, however, the specific water content (wt. of absorbed water/wt. of dry hydrogel) of this PGA hydrogel was approximately 3,500. The specific water content decreased to 200, increasing when the gamma-irradiation dose was over 100 kGy. Under acid conditions or upon the addition of electrolytes, the PGA hydrogels shrunk. The PGA hydrogel was pH-sensitive and the change in the volume of the hydrogel depended on the pH value outside the hydrogel in the swelling medium. This PGA hydrogel was hydrodegradable and biodegradable. A new novel purifier reagent (coagulant), made from the PGA hydrogels, for contaminated turbid water has been found and developed by Japanese companies. A very small amount of this coagulant (only 2 ppm in turbid water) with poly(aluminum chloride) can be used for the purification of turbid water. A PL aqueous solution also can change into a hydrogel by gamma-irradiation. The specific water content of the PL hydrogel ranged from 20 to 160 depending on the preparation conditions. Under acid conditions, the PL hydrogel swelled because of the ionic repulsion of the protonated amino groups in the PL molecules. The rate of enzymatic degradation of the respective PL hydrogels by a neutral protease was much faster than the rate of simple hydrolytic degradation.     

A study on the swelling behavior of poly(acrylic acid) hydrogels obtained by electron beam crosslinking

Poly(acrylic acid) (PAA) hydrogels were prepared by using electron beam (EB) crosslinking of PAA homopolymer from its aqueous solutions. The swelling behavior of the hydrogels was studied as a function of the concentration of PAA solution, radiation dose, pH of the swelling medium and swelling time. Also the environmental pH effect on the water diffusion mode into hydrogels was investigated. These hydrogels clearly showed pH-sensitive swelling behavior with Fickian type of diffusion in the stomach-like pH medium (pH 1.3) and non-Fickian type in the intestine-like pH medium (pH 6.8).     

“Smart” carboxymethylchitosan hydrogels crosslinked with poly(N-isopropylacrylamide) and poly(acrylic acid) for controlled drug release

Carboxymethylchitosan (CMC) hydrogels containing thermo-responsive poly(N-isopropylacrylamide) (poly(NIPAAm)) and pH-responsive poly(acrylic acid) (poly(AA)) were prepared via a free radical polymerization in the presence of hexamethylene-1,6-di-(aminocarboxysulfonate) crosslinking agents. A proper ratio of CMC to NIPAAm and AA used in the reaction was investigated such that the thermo- and pH-responsive properties of the hydrogels were obtained. Water swelling of the hydrogels was improved when the solution pH was in basic conditions (pH 10) or the temperature was below its lower critical solution temperature (LCST). Effects of the change in solution temperature and pH on water swelling properties of the hydrogel as well as the releasing rate of an entrapped drug were also investigated. The hydrogels were not toxic and showed antibacterial activity against Straphylococcus aureus (S. aureus). The pH- and thermo-responsive properties of this novel “smart” hydrogel might be efficiently used as dual triggering mechanisms in controlled drug release applications.