壳聚糖衍生物抗菌研究进展

壳聚糖具有抗菌活性,有广泛的应用前景。为了扩大壳聚糖抗菌活性在不同领域的应用,在壳聚糖分子链上接入不同基团,或螯合金属纳米粒子可得到更强抗菌特性的壳聚糖衍生物。壳聚糖衍生物主要有季铵化壳聚糖、羧甲基化壳聚糖、杂环化合物壳聚糖、壳聚糖衍生物与金属纳米粒子螯合等。本文就不同种类壳聚糖衍生物的抗菌特性进行简要综述。     

N,N-双烷基壳聚糖结构对其自组装泡囊性质的影响

合成了不同主链相对分子质量的N,N-双辛烷基壳聚糖,N,N-双癸烷基壳聚糖及N,N-双十二烷基壳聚糖,并制备了相应的自组装泡囊,比较研究了侧链长度和主链相对分子质量对载药泡囊药物释放行为的影响。结果表明这类N,N-双长链烷基壳聚糖可形成粒径为100～150 nm的泡囊。原子力显微镜表明,侧链长度对N,N-双烷基壳聚糖泡囊的曲率有较明显影响,主链相对分子质量对泡囊的粒径影响较大。药物释放行为表明,侧链长度或主链相对分子质量的增大会导致药物释放速率的降低,达到平衡时的药物释放率也较低,而其相应自组装泡囊的载药量和包埋率却有所提高。     

国外几种阻火聚氨酯泡沫

用卤化羟基取代的亚磷酸醋和磷肟酸(?)作阻火剂的聚氯酯泡沫阻火的聚氨酯泡沫用二异氰酸酯和卤化羟基取代的含磷酸的衍生物反应制得,卤化羟基取代的含磷酸的衍生物用烷基缩水甘油醚和含磷酸的卤化衍生物反应,继后将产物用酸脱烃制得。例如将138克PCl_3,400毫升 CH_2Cl_2和260克特丁基缩水甘油醚混合并加热到40℃,滴加过剩的环氧乙烷并将混合物搅拌3小时,在80℃减压下除去溶剂,得到385克的0-(2-氯乙     

壳聚糖缓释体系研究进展

综述了壳聚糖在缓释系统方面的最新研究进展。包括壳聚糖衍生物缓释体系的研究、壳聚糖缓释体系在医药系统的应用和吸附-控释复合体系的研究,重点介绍了壳聚糖衍生物缓释体系的研究,壳聚糖衍生物缓释体系分为壳聚糖衍生物缓释微球、壳聚糖纳米粒、壳聚糖缓释片、壳聚糖缓释微囊、壳聚糖缓释膜和壳聚糖水凝胶缓释体的研究等六个部分。壳聚糖缓释体系作为一项新技术在医药体系具有广泛的应用前景。     

水溶性丁二酸酐酰化壳聚糖纳米凝胶的制备及其pH响应性研究

以水为介质、碳酸钠为催化剂,室温下制备了水溶性丁二酸酐酰化壳聚糖,研究了反应物料比对产物酰化取代度及水溶性的影响。红外光谱分析表明丁二酸酐成功接枝到了壳聚糖分子链上;XRD结果表明酰化反应改变了壳聚糖的结晶结构;Zeta电位分析发现存在1个等电点:pI=3.54。将丁二酸酐酰化壳聚糖加入到甲酸溶液中,通过自组装法制备纳米凝胶粒子。SEM照片显示该纳米凝胶粒子呈球形,粒径为20~30nm;DLS测试表明,随溶液pH值的增大,粒径从70~80nm增大到350~700nm,表明丁二酸酐酰化壳聚糖纳米凝胶粒子具有一定的pH响应性。     

壳聚糖与肉桂醛的缩合反应制备席夫碱及其抑菌活性研究

通过壳聚糖与肉桂醛在超声波振荡下的反应制备了壳聚糖缩肉桂醛席夫碱。采用[L9(33)]正交实验探讨了反应时间、反应温度及反应物配比对壳聚糖席夫碱反应缩合率和取代度的影响。在最佳条件下壳聚糖席夫碱的缩合率可达89.38%,取代度为0.84。红外光谱和X-射线衍射光谱结果表明衍生物具有壳聚糖席夫碱的结构特征。抗菌实验表明,该衍生物对大肠杆菌、金黄色葡萄球菌和黑曲霉都具有抑制作用,抗菌活性随浓度的增加而增加,且优于壳聚糖。     

N,N-双十二烷基壳聚糖自组装纳米药用泡囊的制备

采用逆相蒸发法首次制备N,N-双十二烷基壳聚糖自组装纳米药用泡囊。实验表明该自组装泡囊同时具有多层结构和多腔室结构,平均粒径在150m左右。N,N-双十二烷基壳聚糖自组装药用泡囊的维生素B12药物包封率为13．42％;载药量分别为0．06mg／mg。载药泡囊的体外药物释放可持续24h左右。     

疏水壳聚糖的制备及其凝血性能

为增强壳聚糖的止血效果,采用酰基化改性在壳聚糖氨基上连接长链烷基以形成疏水性壳聚糖。采用单因素实验对反应温度、月桂酸酐的浓度进行筛选,以疏水壳聚糖的黏度、取代度及凝血效果作为评价指标,通过梯度设计筛选得到的最优工艺条件为:温度55℃,壳聚糖质量分数为1%,月桂酸酐浓度7.84×10-3 mol/L。采用红外、核磁共振、接触角测试仪对其进行了表征,表明合成了疏水壳聚糖。体外凝血实验结果表明:疏水壳聚糖的止血效果与氨基的取代度在一定范围内呈正相关性,当取代度为10.8%和15.9%的疏水壳聚糖与血液分别混合后(疏水壳聚糖在混合物中质量分数不小于0.75%),1~4 s左右可形成稳定的凝胶,从而凝血。又通过小鼠肝脏止血实验发现疏水壳聚糖粉末能够迅速止血,且效果显著优于壳聚糖。     

水溶性壳聚糖纳米粒子的制备及其BSA载药性能

为了避免高分子量壳聚糖水溶性差以及增溶剂乙酸可能带来的负面作用,本文选择低分子量水溶性壳聚糖 (WSC)作研究对象,采用三聚磷酸(TPP)作交链剂制备不同WSC/TPP比率的WSC纳米粒子,并用于牛血清白蛋白 (BSA)的释放载体。经测得为球形形貌的纳米粒子空载和载药时粒径、Zeta电位分别在35～190 nm、35～42 mV。红外光谱及X–射线衍射证实了纳米粒子中WSC的氨基与TPP的磷酸基团发生了交联反应。纳米粒子载药性能试验表明在0.05～1 mg/mL范围内随着BSA浓度的增大,纳米粒子的载药量增加而负载率降低。体外释放实验表明水溶性壳聚糖纳米载体对蛋白质药物具有缓释特征。因此,水溶性壳聚糖有望成为新的载体应用于蛋白质药物的控制释放。     

壳聚糖衍生物的合成及其在化妆品中的应用

综述了目前几类壳聚糖衍生物：羧甲基壳聚糖、羧基壳聚糖、壳聚糖羟烷基衍生物、壳聚糖或酰基化衍生物、壳聚糖磺化衍生物、壳聚糖季铵盐的制备方法．分别介绍了它们的性能和在护肤品、洗发香波、头发调理剂、定型剂以及洗浴剂中的应用，同时举出了较典型的应用实例，为此方面研究工作提供了参考配方。     

Tyrosinase‐mediated in situ forming hydrogels from biodegradable chondroitin sulfate–tyramine conjugates

Tyrosinase‐mediated crosslinking of chondroitin sulfate–tyramine (CS‐TA) conjugates was successfully applied in the preparation of biodegradable in situ forming hydrogels under physiological conditions. Depending on the polymer concentration, the degree of substitution of TA residue and the tyrosinase concentration, the gelation times ranged from 2.3 to 129 min. Studies on the gel contents of CS‐TA hydrogels showed that their degrees of crosslinking could be controlled by varying the tyrosinase concentrations. CS‐TA hydrogels could be completely degraded by the chondroitinase ABC within a time range from 6 days to 11 weeks. CS‐TA hydrogels possessed highly elastic properties and their storage moduli varied from 120 to 1300 Pa, as determined by rheological analysis. Scanning electron microscopy observation confirmed that CS‐TA hydrogels contained a well‐interconnected pore structure. A live–dead assay demonstrated that NIH 3T3 fibroblasts incorporated in CS‐TA hydrogels retained their viability. In addition, in vitro release of methylene blue (a photodynamic therapy drug) from CS‐TA hydrogels could be effectively sustained by the drug encapsulation in the hydrogels. This study indicates that tyrosinase‐mediated in situ forming CS‐TA hydrogels are promising for biomedical applications including drug release and tissue engineering. © 2012 Society of Chemical Industry     

Chitosan/alginate nanoparticles stabilized by poloxamer for the controlled release of 5‐fluorouracil

In this study, stable 5‐fluorouracil (5‐FU)‐loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) were prepared with poloxamer as a surfactant. The effects of the Alg concentration, CS/Alg weight ratio, and poloxamer concentration on the properties of the 5‐FU‐loaded CS/Alg NPs were studied. The results of dynamic light scattering and transmission electron microscopy indicated that stable 5‐FU‐loaded CS/Alg NPs of around 200 nm with low‐size polydispersities were achieved. Furthermore, the in vitro release of the 5‐FU‐loaded CS/Alg NPs was investigated in phosphate buffer solution at pH 7.4. The results show that the encapsulation efficiency of 5‐FU depended on the drug feeding amount (DFA), poloxamer concentration, Alg concentration, and CS concentration. However, the in vitro release rate of the 5‐FU‐loaded CS/Alg NPs was only related to the DFA, Alg concentration, and CS concentration and was independent of the poloxamer concentration. The time of 5‐FU release from the CS/Alg NPs could becontrolled to be sustained for more than 12 h. According to this study, CS/Alg NPs stabilized by poloxamer could serve as a suitable candidate for the controlled release of 5‐FU. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

壳聚糖/聚磷酸铵膨胀阻燃PP的阻燃及抑烟性能

为了提高聚丙烯(PP)的阻燃和抑烟性能,将壳聚糖(CS)作为膨胀型阻燃剂的碳源、聚磷酸铵(APP)作为膨胀型阻燃剂的酸源和气源,在此基础上通过熔融共混的方法制备了PP/CS/APP复合材料。采用极限氧指数仪、锥形量热仪等仪器研究了PP/CS/APP复合材料的的抑烟性及阻燃性。研究结果表明:CS/APP添加量为30%时,复合材料的极限氧指数值最大可达28.1%;且复合材料在烟气释放总量、CO和CO_2排放上明显降低,抑烟性得到了提升;热释放速率峰值、平均热释放速率值、平均有效燃烧热值、总热释放量值降低,成炭率升高,PP/CS/APP复合材料更难点燃;火灾性能指数明显提高,阻燃性能得到了大幅度提升,火灾蔓延指数显著减小,同时火灾危险性也相应降低。     

Nanohybrid structure analysis and biomolecule release behavior of polysaccharide-CDHA drug carriers

Nanoscaled polymer composites were prepared from polysaccharide chitosan (CS) and Ca-deficient hydroxyapatite (CDHA). CS-CDHA nanocomposites were synthesized by in situ precipitation at pH 9, and the CS-CDHA carriers were then fabricated by ionic cross-linking methods using tripolyphosphate and chemical cross-linking methods by glutaraldehyde and genipin. Certain biomolecules such as vitamin B₁₂, cytochrome c, and bovine serum albumin were loaded into the CS-CDHA carriers, and their release behaviors were investigated. Furthermore, these CS-CDHA carriers were examined by transmission electron microscopy, electron spectroscopy for chemical analysis, and X-ray diffraction. The release behavior of the biomolecules was controlled by the CS/CDHA ratios and cross-linked agents. By increasing the concentration of CS and the concentration of the cross-linking agents, cross-linking within carriers increases, and the release rate of the biomolecules is decreased. Moreover, the release rate of the biomolecules from the CS-CDHA carriers at pH 4 was higher than that at pH 10, displaying a pH-sensitive behavior. Therefore, these CS-CDHA hydrogel beads may be useful for intelligent drug release and accelerate bone reconstruction.     

制备CS-Ca2+-SAL中空凝胶球及其对碳纳米的缓释行为

将海藻酸钠溶液(SAL)滴入壳聚糖-钙(CS-Ca2+)分散溶液中，海藻酸钠与壳聚糖分子链之间发生物理交联的同时，也与钙离子进行同步交联，可一步制备毫米级壳聚糖-钙-海藻酸钠(CS-Ca2+-SAL) 水凝胶球。通过调控原料用量比例、滴加速度和方式，成功制备内部中空，球壁均匀，表面致密的凝胶球。以荧光性碳纳米点为标记物，考察凝胶球的溶胀性能和缓释性能。结果表明，凝胶球在中性水溶液中12h溶胀率可达26.09%，并能保持完整球形结构。溶胀性能受到pH的影响显著，处于pH=1.2的溶液体系中溶胀率最小，处于pH =6.8溶液环境中溶胀率最大。荧光凝胶球在pH=7.1的Tris-HCl缓冲液中的释放率实验结果表明，对碳纳米的释放模型最符合Hixon-crowell溶蚀方程，说明凝胶球的缓释机制以溶蚀为主，扩散为辅。     

Electroactive polyacrylamide/chitosan/polypyrrole hydrogel for captopril release controlled by electricity

The demand for the development of new therapies and devices for controlled drug release has been continuously increasing, especially those based on materials sensitives to external stimuli, such as electricity. Therefore, in this work, acrylamide was polymerized in the presence of chitosan (CS), using N,N′-methylenebisacrylamide as cross-linking, followed by immersion in pyrrole aqueous solution and chemical polymerization to obtain an electroactive hydrogel of polyacrylamide/CS/polypyrrole (PA/CS/PPy) (67.5/7.5/25% wt.); this electroactive hydrogel was later used in drug delivery controlled by electricity studies. The synthesized PA/CS/PPy hydrogel was characterized by scanning electron microscopy, FTIR spectroscopy, and thermogravimetric analysis. It was observed that the hydrogel presented pores in the range of 50–200 μm with CS and PPy well incorporated to the cross-linked PA. The hydrogel swelling percentage (S) was determined at different pHs. It was observed that S was independent of pH, with S = 700% and a swelling kinetics described by the Fickian diffusion mechanism at alkaline pH. PA/CS/PPy hydrogel was used to absorb captopril (a drug for hypertension control), and its kinetics release at different applied potentials and pH was studied. Release kinetics were described by the Korsmeyer–Peppas model, while release mechanism was a Case-II transport without current at alkaline pH; under electrical stimuli, the mechanism presented an anomalous transport with ON–OFF profile, increasing the release rate with the applied voltage showing its electroactivity in the captopril release.     

琥珀酰基月桂酰壳聚糖的制备及性能

以丁二酸酐和壳聚糖(CS)为原料合成亲水性琥珀酰基壳聚糖(SCS),然后与月桂酰氯通过酰化反应制备了两亲性的琥珀酰基月桂酰壳聚糖(LSCS)。采用FTIR和1HNMR对壳聚糖衍生物进行了结构表征。LSCS的琥珀酰基的取代度为41.27%,月桂酰基的取代度为6.32%。改性后的壳聚糖在pH<3.0和pH>6.5时溶解度较好,在等电点及附近的pH范围内溶解度降低。LSCS具有较强的分子间相互作用,随其质量分数增加溶液黏度显著增加,且在质量分数达到2%时可形成物理凝胶。该物理凝胶对NaCl浓度较敏感,随着NaCl浓度的增加,凝胶强度减小。     

壳聚糖/ZIF⁃67杂化物的制备及其对环氧树脂阻燃抑烟性能的影响

为了提高环氧树脂（EP）的阻燃抑烟性能,采用共沉淀法将类沸石咪唑酯骨架材料ZIF⁃67负载到壳聚糖（CS）表面,通过傅里叶红外光谱（FTIR）、X射线衍射（XRD）和扫描电子显微镜 （SEM）对其结构和形貌进行分析,结果表明杂化物CS⁃ZIF⁃67成功制备。将不同比例的CS⁃ZIF⁃67添加到EP中,研究其对EP阻燃抑烟性能的影响。结果表明,与纯的EP相比,CS⁃ZIF⁃67的加入可以提高EP复合材料的垂直燃烧UL 94等级和极限氧指数（LOI）、降低EP复合材料的热释放速率（HRR）和烟释放速率（SPR）,提高复合材料燃烧后的残炭量,CS⁃ZIF⁃67的加入可以有效提高EP的阻燃抑烟性能。对EP复合材料燃烧后的残炭进行SEM和Laman光谱分析。结果表明,CS⁃ZIF⁃67的加入,使得残炭的石墨化程度提高,EP燃烧时能形成更加致密的炭层,从而起到阻燃抑烟的作用。     

Preparation of porous chitosan/agarose microsphere and its R‐phycoerythrin release properties

The chitosan microspheres (CS‐CL) were prepared by suspension crosslinking method and used as carriers of R‐phycoerythrin (R‐PE). In this study, R‐PE was loaded in the microspheres and released in vitro. The effects of pH value, temperature, ionic strength, and R‐PE concentration on loading efficiency and release behavior were discussed. A novel microsphere that contained agarose (CS‐AR MP) was prepared and the basic loading and releasing behavior for R‐PE of this kind of new microspheres were also investigated. The results showed that all these chitosan microspheres have the ability to control‐release R‐PE. The addition of agarose may somewhat accelerate the release rate of R‐PE from microspheres and reduce the capacity of adsorption for R‐PE. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2759–2766, 2007     

In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.