三元共聚物温敏性微凝胶的制备及性能研究

以N-异丙基丙烯酰胺(NIPAM)、2-丙烯酰胺-2-甲基丙磺酸(AMPS)和N-叔丁基丙烯酰胺(NT-BA)为共聚单体,N,N-亚甲基双丙烯酰胺(MBA)为交联剂,过硫酸铵(APS)为引发剂,通过无皂乳液聚合的方法制备了一系列三元共聚物温敏性微凝胶。测定结果表明,所得微凝胶具有规则的球形结构且粒径分布均一,引入疏水性单体NTBA能有效调节共聚物微凝胶的低临界溶解温度(LCST),并对其药物负载与释放进行了初步探索。     

LCST可调无规共聚物的相行为及聚集行为

以聚乙二醇甲醚丙烯酸酯(OEGA)和2-(2-乙氧基乙氧基)乙基丙烯酸酯(DEGEEA)为单体通过可逆-加成断裂链转移(RAFT)法合成低临界溶解温度(LCST)可调的水溶性无规共聚物P(OEGA-co-DEGEEA)(POD)。借助核磁共振氢谱、凝胶渗透色谱对该共聚物的化学结构、相对分子质量及其分布进行表征,采用紫外可见分光光度计和动态光散射对其相行为及聚集行为进行研究。结果表明,POD的LCST可通过单体投料比和盐进行调节。OEGA含量和阴离子半径的增加均能使LCST升高。温度低于LCST时,共聚物倾向于分子内聚集;温度高于LCST时,共聚物的聚集方式从分子内向分子间转变,聚集体的粒径与共聚物浓度、盐等有关。     

基于NIPAM和HEMA的温敏性共聚物水溶液性能研究

以N-异丙基丙烯酰胺(NIPAM)、甲基丙烯酸羟乙酯(HEMA)、丙烯酰胺(AM)、丙烯酸(AA)为原料,采用水溶液自由基聚合法制备了N-异丙基丙烯酰胺基温敏水溶性共聚物P(NIPAM-HEMA-AM)和P(NIPAM-HEMA-AM-NaAA)。研究了无机盐及聚合物结构对共聚物低临界溶解温度(LCST)的影响,考察了共聚物浓度、盐浓度、表面活性剂浓度对共聚物溶液流变性能特别是粘温特性的影响。结果显示,随着盐浓度的增加,共聚物溶液的LCST呈下降趋势。共聚物浓度较高时,在LCST附近表现出显著的升温增稠性。在P(NIPAM-HEMA-AM-NaAA)溶液中加入NaCl后溶液黏度增加,升温增稠效应明显。     

温敏水凝胶对疏水性药物的装载及释放行为

聚己内酯-聚乙二醇-聚己内酯(PCL-PEG-PCL)三嵌段共聚物的水溶液,具有低临界溶液温度(LCST),可制备温敏水凝胶,并可作为药物载体应用于生物医学领域。 使用 β-环糊精衍生物作为分子胶囊,在改善疏水性药物的水溶性的同时,提高 PCL-PEG-PCL 水凝胶对疏水性药物的装载和释放能力。 实验中槲皮素作为疏水性药物的模型,由于槲皮素分子与 β-环糊精络合形成微胶囊包装结构,大幅度提高了槲皮素的溶解度;此外槲皮素 / β-环糊精衍生物水溶液中 PCL-PEG-PCL 三嵌段聚合物,也快速溶解形成共混溶液,当温度提高到体温时,迅速变成凝胶状态。 在缓冲溶液中进行了槲皮素药物的释放实验,实现了 PCL-PEG-PCL 水凝胶对疏水性药物的缓释效果,在缓释过程中 β-环糊精衍生物也充当了药物释放载体的作用。     

疏水改性聚丙烯酰胺P(AM/DiC_8AM)的合成及性能

采用二元单体胶束共聚,合成了孪尾疏水改性丙烯酰胺/N,N-二辛基丙烯酰二元共聚物[简称P(AM/DiC8AM)],成功引入了疏水单体.用FTIR分析了各基团峰的归属,证明了共聚物为带有疏水基团的二元共聚物.特性粘数的测定结果表明:分子量M、疏水单体含量[H]增加,特性粘数[η]增大,Huggins常数KH减少,平均线团密度ρequ减少;但随疏水链嵌段长度NH的增加,[η]们增大,KH同样增大.随疏水单体含量[H]、分子量M、疏水链的嵌段长度NH增加,各聚合物溶液临界缔合浓度cac降低,疏水缔合的机率增加.     

阴离子长链疏水缔合水溶性聚合物的合成及溶液性能

利用溶液聚合制备了离子型疏水缔合水溶性共聚物P(AM/AMPS/C11AM),在共聚物结构中引入了既带有疏水长链又带有可离子化的基团,红外光谱确认了所合成的共聚物为目标共聚物;P(AM/AMPS/C11AM)系列共聚物溶液的表观黏度与共聚物浓度有很大关系,即使在极低的共聚物溶液浓度下也具有很好的增粘效果;在一定温度,一定pH值和表面活性剂的条件下,研究了系列共聚物溶液行为,结果与接枝疏水单体改性的丙烯酰胺是不同的。荧光光谱研究证实了共聚物在水溶液中的缔合行为。     

荧光探针研究温敏大分子单体在水溶液中的热缔合行为

通过芘荧光探针研究了基于双丙酮丙烯酰胺(DAAM)的新型温敏大分子单体在溶液中的热缔合行为。结果表明,温敏大分单体的临界缔合浓度(CAC)取决于丙烯酰胺(AM)与DAAM的组成比。DAAM的比例越大,CAC就越低;随着温敏大分子单体中DAAM的含量、大分子单体浓度和溶液pH的增加,芘的I1/I3值降低,疏水缔合作用增强,且温度越高,I1/I3值越低,呈现明显的热缔合行为。温敏大分单体的热缔合行为随组成、浓度和pH变化的这种性质有可能在新型温敏聚合物及凝胶的合成设计上获得应用。     

磺酸甜菜碱与阴离子单体共聚物的合成及溶液性质

合成了N、N-二甲基-N-甲基丙烯酰氧乙基-N-丁基磺酸铵(DMABS)及其与三种阴离子单体——丙烯酸(AAc)、丙烯酸钠(NaAAc)、对乙烯基苯磺酸钠(NaSS)的无规共聚物,并通过核磁共振(1H-NMR)与凝胶渗透色谱-多角度激光光散射(GPC-MALLS)等表征了单体与共聚物的结构。探讨了共聚物稀溶液的相分离温度(TPT),随单体组成、聚合物浓度、溶液pH值与离子强度的变化。结果显示,疏水性单体的引入导致共聚物/水体系的TPT进一步升高;而亲水性单体的引入则显著降低共聚物/水体系的TPT。     

双重磁响应温敏复合微球的制备及表征

在Fe3O4纳米粒子表面聚合包覆温敏性聚N-异丙基丙烯酰胺(PNIPAM)及其与聚苯乙烯(PS)、聚α-甲基丙烯酸(PMAA)的共聚物,制备表面不同亲水/疏水性质的双重磁响应温敏复合微球。利用透射电镜(TEM)、红外光谱(FT-IR)及Zeta粒度仪(DLS)等对复合微球进行了表征。结果表明,复合微球呈现核壳结构,粒径约为150nm~300nm;在复合微球温敏聚合物中引入亲水/疏水链段可以有效调节其最低临界溶解温度(LSCT),随着温敏聚合物亲水性的提高,微球LSCT向高温移动,且该微球具有良好的双重磁响应特性(磁靶向响应性和磁热响应性)。     

聚合物P(NaAMPS-VCL-DVB)分子结构对其温敏缔合行为的影响

采用可见分光光度计、变温核磁共振氢谱、流变仪等,从浊点和黏度变化方面研究了2-甲基-2-丙烯酰胺基丙磺酸钠(NaAMPS)/N-乙烯基己内酰胺(VCL)/二乙烯苯(DVB)聚合物PAVD在水溶液中的温敏缔合作用,揭示了PAVD分子结构对其温敏缔合作用的影响规律。可见分光光度计和变温核磁共振氢谱对PAVD水溶液相变过程的跟踪研究表明,聚合物分子中VCL含量越高,浊点越低,且变温核磁共振氢谱测试表明,PAVD分子VCL侧链上亚甲基链段会随着温度的升高而变为疏水性,进而产生疏水缔合作用;流变测试表明,只有当聚合物分子中VCL含量处于一定范围内时,其溶液会出现明显的温敏增稠现象,且VCL含量越高,临界增稠温度越低,温敏增稠现象越显著。最后基于临界增稠温度和浊点的对比分析,对聚合物水溶液的温敏缔合过程进行探讨。     

Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for drug delivery

A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) segment was designed and synthesized. The structure of the copolymer was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The copolymer may self-assemble into micelles in water, with the hydrophobic POA segments at the cores of micelles and the hydrophilic PNIPAAm segments as the outer shells. The resulting micelles demonstrate temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow size range of approximately 10-30 nm. A study of controlled release reveals that the self-assembled micelles have great potential as drug carriers.     

Thermosensitive behavior in cell culture media and cytocompatibility of a novel copolymer: poly(N-isopropylacrylamide-co-butylacrylate)

Cell sheet technology is a promising step forward in tissue engineering. Cell sheets are usually generated using Poly(N-isopropylacrylamide) hydrogels due to their swelling change around the lower critical solution temperature (LCST). Nevertheless, LCST can be affected by cell culture medium components and therefore it is necessary to ensure that the polymer preserves its thermosensitivity under these conditions. We propose a novel thermosensitive crosslinked-copolymer: Poly(N-isopropylacrylamide-co-butylacrylate). This copolymer is shown to be cytocompatible and thermosensitive under cell culture medium conditions, and besides, it can be synthesized inexpensively. Thermosensitivity was investigated by determining the LCST with differential scanning calorimetry and swelling/ratio measurements. Cytocompatibility and capacity to deliver cell sheets were studied employing 3T3 and human oral epithelial cells. In conclusion, we obtained a thermosensitive copolymer that allows cell sheet formation/detachment by using a simple and low-cost polymerization method. Furthermore, crosslinking allows easy manipulation of cell sheets growing on the copolymer for potential in situ applications.     

Novel thermosensitive flocculanting agent based on pullulan

New thermosensitive polysaccharide (P-g-pNIPAAm) was synthesized by graft-polymerization of p(N-isopropylacrylamide) (pNIPAAm) onto pullulan (P) using Ce(IV) ion as initiator. The grafted polysaccharide was characterized by FT-IR and ¹H NMR spectroscopy and elemental analysis. Its flocculation efficiency was studied in a clay suspension, in comparison with p(NIPAAm) homopolymer, as a function of the polymer dose, temperature and settling time. The thermosensitive polysaccharide could induce clay particle flocculation both below and above the lower critical solution temperature (LCST), but the process was more effective above the LCST. A lower value of the residual turbidity at the optimum polymer dose and a wider flocculation window were recorded at temperature above the LCST. The floc size distribution and surface morphology revealed bigger size flocs when the flocculation was performed above the LCST. The re-dispersion effect was negligible for the flocs obtained in the presence of P-g-pNIPAAm.     

Synthesis and self-assembly of tunable thermosensitive chitosan amphiphilic copolymers by click chemistry

Amphiphilic chitosan-graft-P(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate) (CS-g-P(MEO₂MA-co-OEGMA)) copolymers were synthesized by the “graft onto” method via click chemistry. The graft copolymers were characterized by ¹H NMR and ATR FT-IR measurements. The self-assembly behavior and tunable thermosensitive properties of CS copolymers in water were investigated by TEM, DLS, and transmittance. The lower critical solution temperature (LCST) values of CS copolymer micelle solutions were tuned by altering the molar ratio of MEO₂MA and OEGMA in copolymers. Furthermore, the copolymer micelles can reversibly swell and shrink in response to external temperature. The obtained tunable thermosensitive amphiphilic CS copolymers have both the unique properties of P(MEO₂MA-co-OEGMA) and chitosan, and will have the potential applications in the biomedical field.     

活性可控自由基聚合法制备含纳米二氧化硅的星形丙烯酰胺共聚物

以单电子转移活性自由基聚合(SET-LRP)法,在水溶液中合成含纳米二氧化硅的新型星形水溶性共聚物,研究了单体、引发剂、催化剂、配体和改性纳米SiO2功能单体(NSFM)用量、单体摩尔比等条件对聚合反应的影响。采用红外光谱和核磁共振氢谱对制备的丙烯酰胺共聚物进行表征。结果表明,NSFM成功地参与了单电子转移活性自由基聚合反应中。通过正交试验确定了聚合反应的最佳物料摩尔比,即n(AM)∶n(AANa)∶n(Gly-Br3)∶n(CuBr)∶n(Me6TREN)=1687.5∶562.5∶1.0∶2.3∶1.5,[AM]+[AANa]+[NSFM]总浓度为4.5mol/L;单因素实验确定了NSFM的最佳用量为单体总质量的0.5%。用流变仪对共聚物的性能进行了研究。结果表明,当剪切速率超过临界值(100s-1)时,星形共聚物表现出剪切增稠的流变性能;P(AM-co-AANa-co-VTS-SiO2)表现出较好的耐温和抗盐性。     

Synthesis and characterization of a thermo-sensitive poly(N-methyl acryloylglycine methyl ester) used as a drug release carrier

In this article, poly(N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by ¹H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers (N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.     

Synthesis and characterization of a thermo-sensitive poly(<Emphasis Type="Italic">N</Emphasis>-methyl acryloylglycine methyl ester) used as a drug release carrier

In this article, poly(N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by ¹H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers (N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.     

Synthesis, swelling and drug release behavior of poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) hydrogel

In this study, poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) (poly(DEA-co-NHMAA)) hydrogels were synthesized by changing the initial DEA/NHMAA mole ratio, N,N'-methylenebisacrylamide and total monomer concentration. The thermosensitive and mechanical performances were optimized by altering the above parameters. The hydrogels were characterized by using Fourier transform infrared (FTIR) spectroscope and scanning electron microscope (SEM). In comparison with the PDEA hydrogel, the equilibrium swelling ratio (ESR) and lower critical solution temperature (LCST) of the hydrogels increased with the increase of NHMAA content in the feed. The swelling kinetics was also studied. The release behaviors of the model drug, aminophylline, are found dependent on hydrogel composition and environmental temperature, which suggests that these materials have potential application as intelligent drug carriers.     

Synthesis and characterization of mesoporous silica/poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) functional hybrid useful for drug delivery

Recent studies indicate the use of mesoporous silica and polymeric sensitive hydrogels as suitable for drug delivery systems due to their specific characteristics. Polymeric hydrogels, such as poly(N-isopropylacrylamide) [P(N-iPAAm)], show volumetric expansion/contraction behaviour at 306 K, which that can be used to develop a thermosensitive drug delivery system. In this study, we report a facile and direct synthesis route to obtain hybrid functional nanosystems based on silica-P(N-iPAAm) by using a neutral surfactant and without any functionalization method and the assessment of its release rate of a model drug. The materials were characterized by Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy, transmission electron microscopy and thermal analysis. A release assay with atenolol monitored by UV–Vis spectroscopy was performed for pure SBA-15 and a hybrid system at different temperatures in order to evaluate the influence of the thermosensitive behaviour of the polymer on the release kinetics. The response of the hybrid system as a drug delivery device is influenced by the volumetric contraction of P(N-iPAAm) up to the lower critical solution temperature (LCST) due to phase transition. Above the LCST, drug release depends essentially on the temperature.     

氟碳丙烯酸酯对聚丙烯酰胺的改性

用N-丙基,N-羟乙基全氟辛基磺酰胺(FC)与丙烯酸反应得到了N-丙基,N-羟乙基全氟辛基磺酰胺丙烯酸酯(FCA),再通过与丙烯酰胺共聚得了氟碳改性聚丙烯酰胺P(AM—FCA)。考察了共聚物中FCA单体含量、溶液温度、盐浓度、P(AM—FCA)质量分数对溶液粘度的影响．结果表明．在实验范围内．共聚物溶液的表现粘度随P(AM—FCA)质量分数和盐浓度的增加而增加,随溶液温度和FCA单体含量的增加出现极值,共聚物和聚丙烯酰胺相比,具有良好抗温、耐盐性能,可望作为三次采油用驱油荆。