Thermo- and pH-sensitive poly(vinylmethyl ether)/carboxymethylchitosan hydrogels crosslinked using electron beam irradiation or using glutaraldehyde as a crosslinker

BACKGROUND: Stimuli-sensitive or intelligent hydrogels have been investigated for many biomedical and pharmaceutical applications. Those hydrogels with dual sensitivity will have more extensive potential applications. The aim of the work presented was to prepare a series of thermo- and pH-sensitive hydrogels based on poly(vinylmethyl ether) (PVME) and carboxymethylchitosan (CMCS). The hydrogels were crosslinked using electron beam irradiation (EB) or using glutaraldehyde (GA) as a crosslinker at room temperature.

PLLA-PCys co-electrospun fibers for capture and elution of glutathione S-transferase

The copolymer poly(L-lactic acid)-b-poly(L-cysteine) (PLA-b-PCys) was co-electrospun with PLGA into ultrafine fibers. The reduced glutathione (GSH) was conjugated to the fiber surfaces via disulfide bonds. The glutathione S-transferase (GST) was captured onto the GSH fibers via specific substrate-enzyme interaction between the bound GSH and GST. The captured GST was eluted with free GSH aqueous solution and lyophilized to get pure GST powders. The results show that the GSH moieties on the fiber surface retain the bioactivity of the free GSH and thus they can bind specifically with GST and the GST in solution is captured onto the fiber surface. In addition, the bound GSH is not as active as free GSH so that the captured GST can be eluted off from the fiber by free GSH aqueous solution. Based on this principle, GST itself or its fused proteins can be separated and purified very easily. The preliminary purification efficiency is 6.5 mg center dot(g(PCys))(-1). Further improvements are undertaken.

Self-assembly morphology effects on the crystallization of semicrystalline block copolymer thin film

Self-assembly morphology effects on the crystalline behavior of asymmetric semicrystalline block copolymer polystyrene-block-poly(L-lactic acid) thin film were investigated. Firstly, a series of distinctive self-assembly aggregates, from spherical to ellipsoid and rhombic lamellar micelles (two different kinds of rhombic micelles, defined as rhomb 1 and rhomb 2) was prepared by means of promoting the solvent selectivity. Then, the effects of these self-assembly aggregates on crystallization at the early stage of film evolution were investigated by in situ hot stage atomic force microscopy. Heterogeneous nucleation initiated from the spherical micelles and dendrites with flat on crystals appeared with increasing temperature. At high temperature, protruding structures were observed due to the thickening of the flat-on crystals and finally more thermodynamically stable crystallization formed. Annealing the rhombic lamellar micelles resulted in different phenomena. Turtle-shell-like crystalline structure initiated from the periphery of the rhombic micelle 1 and spread over the whole film surface in the presence of mostly noncrystalline domain interior. Erosion and small hole appeared at the surface of the rhombic lamellar micelle 2; no crystallization like that in rhomb 1 occurred. It indicated that the chain-folding degree was different in these two micelles, which resulted in different annealing behaviors.

Synthesis of novel functional polyolefin containing carboxylic acid via Friedel-Crafts acylation reaction

The strong polar group, carboxylic acid, has triumphantly been introduced into ethylene and allylbenzene copolymers without obvious degradation or crosslinking via Friedel-Crafts (F-C) acylation reaction with glutaric anhydride (GA), succinic anhydride (SA) and phthalic anhydride (PA) in the presence of anhydrous aluminum chloride in carbon disulfide. Some important reaction parameters were examined in order to optimize the acylation process. In the optimum reaction conditions, almost all of the phenyls can be acylated with any anhydride. The microstructure of acylated copolymer was characterized by Fr-IR, H-1 NMR and H-1-H-1 COSY. All the peaks of acylated copolymers can be accurately attributed, which indicates that all the acylation reactions occur only at the para-positions of the substituent of the aromatic rings. The thermal behavior was studied by differential scanning calorimetry (DSC), showing that the melting temperatures (T(m)s) of acylated copolymers with GA firstly decrease slowly and then increase significantly with the increase of the amount of carboxyl acid groups.

Enantiomeric PLA-PEG block copolymers and their stereocomplex micelles used as rifampin delivery

A novelty approach to self-assembling stereocomplex micelles by enantiomeric PLA-PEG block copolymers as a drug delivery carrier was described. The particles were encapsulated by enantiomeric PLA-PEG stereocomplex to form nanoscale micelles different from the microspheres or the single micelles by PLLA or PDLA in the reported literatures. First, the block copolymers of enantiomeric poly(L-lactide)-poly(ethylene-glycol) (PLLA-PEG) and poly(D-lactide)-poly(ethylene-glycol) (PDLA-PEG) were synthesized by the ring-opening polymerization of L-lactide and D-lactide in the presence of monomethoxy PEG, respectively. Second, the stereocomplex block copolymer micelles were obtained by the self-assembly of the equimolar mixtures of enantiomeric PLA-PEG copolymers in water. These micelles possessed partially the crystallized hydrophobic cores with the critical micelle concentrations (cmc) in the range of 0.8-4.8 mg/l and the mean hydrodynamic diameters ranging from 40 to 120 nm. The micelle sizes and cmc values obviously depended on the hydrophobic block PLA content in the copolymer.Compared with the single PLLA-PEG or PDLA PEG micelles, the cmc values of the stereocomplex micelles became lower and the sizes of the stereocomplex micelles formed smaller. And lastly, the stereocomplex micelles encapsulated with rifampin were tested for the controlled release application.

Self-assembly of crystalline-coil diblock copolymer in solvents with varying selectivity: From spinodal-like aggregates to spheres, cylinders, and lamellae

We have investigated systematically the morphology of thin films spin-coated from solutions of a semicrystalline diblock copolymer, poly(L-lactic acid)-block-polystyrene (PLLA-b-PS), in solvents with varying selectivity. In neutral solvents (chloroform and tetrahydrofuran (THF)), a spinodal-like pattern was obtained and the pattern boundary was sharpened by diluting the solution. Meanwhile, loose spherical associates, together with larger aggregates composed of these associates by unimer bridges, formed partly due to crystallization of the PLLA blocks in relatively concentrated solutions. In slightly PS-selective solvent (e.g., benzene), both loose and compact spherical micelles were obtained, depending on the polymer concentration, coexisting with unimers. When enhancing the selectivity with mixed solvents, for example, mixing the neutral solvent and the slightly selective solvent with a highly PS-selective solvent, CS2, loose assemblies (nanorods in CS2/THF mixtures and polydisperse aggregates in CS2/benzene mixtures) and well-developed lamellar micelles were obtained.

BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells

The purpose of the present study was to develop implantable BCNU-toaded poly(ethylene glycol)poly(L-lactic acid) (PEG-PLLA) diblock copolymer fibers for the controlled release of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU was well incorporated and dispersed uniformly in biodegradable PEG-PLLA fibers by using electrospinning method. Environmental Scanning Electron Microscope (ESEM) images indicated that the BCNU-loaded PEG-PLLA fibers looked uniform and their surfaces were reasonably smooth. Their average diameters were below 1500 nm. The release rate of BCNU from the fiber mats increased with the increase of BCNU loading amount. In vitro cytotoxicity assay showed that the PEG-PLLA fibers themselves did not affect the growth of rat Glioma C6 cells. Antitumor activity of the BCNU-loaded fibers against the cells was kept over the whole experiment process, while that of pristine BCNU disappeared within 48 h. These results strongly suggest that the BCNU/PEG-PLLA fibers have an effect of controlled release of BCNU and are suitable for postoperative chemotherapy of cancers.

Preparation of core-sheath composite nanofibers by emulsion electrospinning

Uniform core-sheath nanofibers are prepared by electrospinning a water-in-oil emulsion in which the aqueous phase consists of a poly(ethylene oxide) (PEO) solution in water and the oily phase is a chloroform solution of an amphiphilic poly(ethylene glycol)-poly(L-lactic acid) (PEGPLA) diblock copolymer. The obtained fibers are composed of a PEO core and a PEG-PLA sheath with a sharp boundary in between. By adjusting the emulsion composition and the emulsification parameters, the overall fiber size and the relative diameters of the core and the sheath can be changed. A mechanism is proposed to explain the process of transformation from the emulsion to the core-sheath fibers, i.e., the stretching and evaporation induced de-emulsification. In principle, this process can be applied to other systems to prepare core-sheath fibers in place of concentric electrospinning and it is especially suitable for fabricating composite nanofibers that contain water-soluble drugs.

Biodegradable electrospun fibers for drug delivery

The influences of surfactants and medical drugs on the diameter size and uniformity of electrospun poly(L-lactic acid) (PLLA) fibers were examined by adding various surfactants (cationic, anionic, and nonionic) and typical drugs into the PLLA solution. Significant diameter reduction and uniformity improvement were observed. It was shown that the drugs were capsulated inside of the fibers and the drug release in the presence of proteinase K followed nearly zero-order kinetics due to the degradation of the PLLA fibers. Such ultrafine fiber mats containing drugs may find clinical applications in the future.

Preparation and properties of polyimide films codoped with barium and titanium oxides

Polyimide hybrid films containing bimetalic compounds were obtained by codoping poly(amic acid) with a barium and titanium precursor prepared from BaCO3, Ti(OBu)(4), and lactic acid followed by casting and thermal curing. FTIR, WAXD, and XPS measurements showed that barium and titanium precursor could be transformed to BaTiO3 at a temperature above 650 degreesC, while the mixed oxides were only found in hybrid films. The measurements of TEM and AFM indicated a homogeneous distribution of inorganic phase with particle sizes less than 50 nm. The hybrid films exhibited fairly high thermal stability, good optical transparency, and promising mechanical properties. The incorporation of 10 wt % barium and titanium oxide lowered surface and volume electrical resistivity by 2 and 5 orders, respectively, increasing dielectric constant from 3.5 to 4.2 and piezoelectric constant from 3.8 to 5.2 x 10(-12) c/N, relative to the nondoped polyimide film.

SYNTHESIS AND CHARACTERIZATION OF POTENTIALLY BIODEGRADABLE THERMOTROPIC POLYESTERS BASED ON P-HYDROXYBENZOIC ACID AND GLYCOLIC ACID

The synthesis of novel thermotropic liquid crystalline copolyesters derived from aliphatic hydroxy acid (glycolic acid, GA) and aromatic hydroxy acid (p-hydroxybenzoic acid, PHBA) via a melt-copolycondensation process in the presence of various catalysts

Determination of sexual hormones in liquid cosmetics by polymer monolith microextraction coupled with high performance liquid chromatography

A method was presented for the determination of testosterone, methyltestosterone and progesterone in liquid cosmetics by coupling polymer monolith microextraction (PMME) to high performance liquid chromatography with UV detection. A poly (methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column was selected as the extraction medium, which showed high extraction capacity towards these compounds. To achieve optimum extraction performance, several parameters relating to PMME were investigated, including extraction flow rate and pH value, inorganic salt and organic phase concentration of the sample matrix. By simple dilution with phosphate solution and filtering, the sample solution then could be directly injected into the device for extraction. The limits of detection of testosterone, methyltestosterone and progesterone were calculated to be 2, 3, 2, 8 and 4.6 mu g/L. Good linearity was achieved in the range of 10 to 1000 mu g/L with a linear coefficient. r value above 0. 996. Excellent method reproducibility was found by intra- and inter-day precisions, yielding the relative standard deviations of < 7. 7 % and < 7. 5 %, respectively. Recovery for them in the real samples was between 83% and 119%.

Effects of several organic acids on the feeding behavior of Tilapia nilotica

Automatic recording of the frequency of feeding 'bites' was used to evaluate the effects of several organic acids (citric, metacectonic, lactic, acetic, and oxalic) on the stimulatory feeding behavior of Tilapia nilotica . Some of these acids are added to food stocks to retard spoilage. The results showed that citric acid at a concentration of 10(-2) to 10(-6) m, metacetonic acid at 10(-4) to 10(-6) m, and lactic acid at 10(-2) to 10(-5) m stimulated feeding. Fish tended to avoid metacetonic acid at 10(-3) m and acetic acid at 10(-3) m. Acetic acid at 10(-5) m and oxalic acid at 10(-6) m had no significant effects on fish feeding.

功能化乳酸类聚合物的生物应用研究

乳酸类聚合物具有广泛的生物学和医学应用潜力，但是乳酸类聚酯主链缺少活性位点限制了其应用的范围。用聚乙二醇与聚乳酸共聚进行改性，可以提高担载水溶性药物的效率和控释能力；氨基酸改性再偶联生物分子可以实现乳酸类聚合物的生物功能化和生物智能化的应用。本论文以功能化乳酸类聚合物为研究对象，按照聚乳酸生物功能由低级到高级的顺序分别考察了乳酸类聚合物作为载药纤维、表面活性材料、蛋白质固载和纯化材料、以及靶向药物载体等在一些生物领域的应用，并获得结果如下：1） 聚乙二醇改性的聚乳酸嵌段共聚物纺丝担载阿霉素，具有体内和体外的长效缓释作用；2）以biotin/PLL—PLA—PEG制备的高分子涂层，具有良好的特异性固载生物分子；3）将biotin/PLL—PLA—PEG与PLGA共混制备生物活性纤维，则特异性的固载蛋白质；4）用聚半胱氨酸改性聚乳酸合成PCys—PLA，再和PLGA共混制备纤维，再表面偶联还原型谷胱甘肽，则可以捕获谷胱甘肽转移酶；5）将folate/PLL—PLA—PEG制备成胶束，则具备了叶酸受体介导的生物智能化靶向送药的功能，尤其是在动物肿瘤模型的试验中表现了良好的叶酸受体靶向性。

西藏齿突蟾蝌蚪冷适应策略研究

本文通过对高海拔两栖类西藏齿突蟾(Scutiger boulengeri)蝌蚪在实验室特定低温条件下的冷适应微空间行为分布的动态变化分析、温度耐受性实验及在不同适应温度的乳酸脱氢酶(LDH)同工酶的酶量与活性比较分析, 探讨了高海拔两栖类蝌蚪的部分冷适应策略。 西藏齿突蟾蝌蚪在不同温度的行为分布是一连续、动态过程，需用多种检验方法综合利用才能进行判断；在15℃, 除低海拔分布的西藏齿突蟾种群外所有实验物种蝌蚪均符合负二项分布、NeymanⅡ型分布；在10℃, 高海拔两栖类蝌蚪均符合负二项分布、NeymanⅡ型分布；在5℃、0℃低温时，高海拔两栖类不同分组的西藏齿突蟾蝌蚪的负二项分布、NeymanⅡ型分布均呈现明显差异, 这可能与高海拔两栖类蝌蚪在低温条件下通过不断地改变其行为分布方式来避免自身被冻伤有关。野外观察表明：高海拔两栖类蝌蚪常选择与流动河水相连的静水水体这种微生境中生存, 蝌蚪应对环境温度极端变化会不断改变其行为分布方式来选择最佳生存温度以避免极端高、低温对自身身体的伤害, 这种对微生境的利用能力对高海拔两栖类蝌蚪耐受极端环境温度的变化极其重要。 两栖类蝌蚪的温度耐受性实验表明不同的驯化温度可以改变西藏齿突蟾蝌蚪、两栖类仙琴水蛙蝌蚪的最适温度、逃避温度，并具有显著影响。 随着驯化温度5℃、10℃逐渐升高, 其最适温度、逃避温度也在一定范围内升高，但驯化温度对低海拔的仙琴水蛙蝌蚪的最适温度、逃避温度的改变效应大于高海拔的西藏齿突蟾蝌蚪的改变效应, 仙琴水蛙蝌蚪对温度的耐受范围、最适温度和逃避温度的ARRS值都大于西藏齿突蟾蝌蚪, 这说明仙琴水蛙蝌蚪对环境温度变化的适应能力大于西藏齿突蟾蝌蚪。 高海拔地区不同分组的两栖类蝌蚪, 在0℃适应温度时, LDH5条带的酶相对含量最高，而在5℃、10℃、15℃适应温度时，LDH5条带的酶相对含量明显都降低, 这表明酵解作用是高海拔两栖类蝌蚪的一些组织在低温﹑缺氧环境中的重要供能方式。高海拔两栖类蝌蚪同一分组的LDH总酶活性总是表现为10℃适应温度的总酶活性最高，而对低海拔的两栖类蝌蚪则是0℃适应温度的总酶活性最高, 这说明高海拔两栖类蝌蚪的LDH同工酶A、B两亚基基因活性在10℃时最高, 而低海拔两栖类蝌蚪的LDH同工酶A、B两亚基基因活性在0℃时最高。同时发现在15℃适应温度组的高海拔两栖类蝌蚪的LDH电泳图谱都有第6条带,有可能由LDH - C亚基组成, 对高海拔两栖类蝌蚪的LDH - C亚基只在15℃适应温度下才表达的机理还有待进一步的研究。 高海拔两栖类西藏齿突蟾蝌蚪通过行为分布方式的改变来选择最佳的生存温度, 这种温度选择过程与野外特定的微生境的存在密切相关, 现在由于人类对河道的不合理利用正在导致高海拔两栖类蝌蚪赖以生存的这种微生境逐渐消失, 这种微生境的消失将加速高海拔的两栖类种群数量衰退的进程。高海拔两栖类物种蝌蚪在低温（0℃）上表现出的同工酶多谱带说明，其A、B两亚基都有所表达，及其参与代谢的方式也是正常的，而低海拔两栖类物种蝌蚪只有A亚基表达的LDH5存在，因此其主要参与酵解过程，这种通过动物自身生理代谢方式的改变来适应极端环境温度条件的变化是高海拔两栖类蝌蚪能适应低温环境的重要策略。但高海拔物种的适应温度变化范围显著小于低海拔物种，对环境温度的变化适应能力有限，特别是对高温区域，因此全球气候变化可能对高海拔物种影响更为显著。 The partly cold-adaptation stratagem of the high altitude amphibian tadpole were researched in the laboratory by analyzing the high altitude amphibian tadpole of Scutiger boulengeri mainly on endpoints related to the dynamic variation of the micro-spatial behavior distribution patterns, the experiment of the temperature tolerance, and the enzyme content and activity of the lactic acid dehydrogenase(LDH) isozyme in special temperature condition. The behavior distribution of the Scutiger boulengeri tadpole is continuous and variable, but it can be figured out by multple testing ways. At 15℃, all of the experiment amphibian tadpoles behavior distribution fit both for the negative binomial distribution and NeymanⅡtype distribution except for the low altitude Scutiger boulengeri tadpoles. At 10℃, all of the high altitude amphibian tadpoles behavior distribution fit both for the negative binomial distribution and NeymanⅡtype distribution. At lower temperature, 5℃ and 0℃, the high altitude amphibian tadpoles of the Scutiger boulengeri at different groups behavior distribution fit for or don’t fit for behavior distribution respectively. It is denoted that the high altitude amphibian tadpoles probably avoid frostbiting by varying the behavior distribution patterns at low temperature condition. The high altitude amphibian tadpoles often actively select the special microhabitat which has the connected still water body and the flowing water body in the wild. It is important that tadpoles can endure the extreme temperature variety in this kind of microhabitat, because tadpoles can be better survival through select temperature condition through migrating in these kinds of microhabitats by varying their own behavior distribution patterns. Different acclimation temperature causes the significant change of preferred temperature(PT)、 avoiding temperature(AT) both in high altitude amphibian Scutiger boulengeri tadpoles and in low altitude amphibian Rana daunchina tadpoles in the temperature endurance experiment. With the acclimation temperature growing from 5℃ to 10℃. the PT and the AT of them would be uprise to some extent, but the effect of acclimation temperature on the PT and the AT of the tadpoles of Rana daunchina is more significant than the ones on the tadpoles of Scutiger boulengeri, at the same, the effects on the temperature endurance range, the ARRs of the tadpoles of Rana daunchina would be stronger than the ones on the tadpoles of Scutiger boulengeri. It is implied that the adaptation ability of tadpoles of Rana daunchina to the surroundings temperature alternation preferred to tadpoles of Scutiger boulengeri. At 0℃ acclimation temperature, the LDH5 enzyme comparative content of the high altitude amphibian tadpoles at different groups was highest, but it becomes lower at 5℃、10℃、15℃ acclimation temperature. It indicated that the alcoholysis role was the important ways of applying energy for special tissue of the high altitude amphibian tadpoles in low-temperature and low-oxygen condition. The total enzyme activity of the LDH of the high altitude amphibian tadpoles in the same group always keeps the highest at 10℃ acclimation temperature, but the low altitude amphibian tadpoles’ was maximum at 0℃. It was denoted that the gene activity of LDH -A and LDH – B submit was highest at 10℃ acclimation temperature for the high altitude amphibian tadpoles, but the low altitude amphibian tadpoles’ was maximum at 0℃. Meanwhile, the LDH electrophoretogram of the high altitude amphibian tadpoles always composed of 6 stripes at 15℃ acclimation temperature，the extra stripe probably was composed by LDH-C submit。It is unknown why LDH-C expresses only under high temperature。. The high altitude amphibian tadpoles can select the most optimal temperature by changing their behavior distribution patterns ceaselessly, but this course of selecting the most suitable temperature correlated with the special microhabitat in the wild closely. Nowadays, this kind of microhabitat which the high altitude amphibian tadpoles rely on are lossing gradually for human being exploit the riverway unreasonably. The disappearing of the microhabitat would accelerate the decline of the high altitude amphibian population. Compare to one band of LDH5, which only composed by the LDH-A submit, presents in the low altitude amphibian at 0℃, the five bands which composed by the LDH-A and LDH-B are checked out, this means the species which occurred in the highland is more adaptable to the low temperature. It is an important stratagem for the high altitude amphibian tadpoles adapt to the limited low temperature depends on the animal energy metabolism change.However, this kind of adaption is restricted, the adaption range to the temperature is much norrow in the high altitude amphibian than in the low one, especially for the high temperature side. The global climate change will be more serious for the high altitude species.