叶酸和聚乙二醇接枝作基因载体用壳聚糖的合成与表征

本研究将叶酸和聚乙二醇接枝到四种不同分子量的壳聚糖氨基侧链上,以改善壳聚糖的靶向性和水溶性作基因载体。用FTIE、1HNMR、UV-Vis、DSC和TEM对产物进行了表征,结果表明,叶酸和聚乙二醇被成功地接枝到壳聚糖上,所制得的载体有望作为潜在的肿瘤细胞靶向基因载体。     

水溶性量子点的制备及其与壳聚糖衍生物的自组装

以3-巯基丙酸(HS-CH2CH2COOH)为稳定剂, 制备了水溶性的碲化镉(CdTe)量子点(QDs), 考察了制备条件对QDs荧光性能的影响及CdTe QDs与壳聚糖及叶酸和聚乙二醇改性的壳聚糖的自组装. 研究发现, 壳聚糖及改性壳聚糖与QDs的复合物荧光强度相对纯的CdTe QDs明显增强, 且QDs被包裹在内核, 复合粒子呈明显的核/壳结构. 改性壳聚糖/QDs复合物较小且尺寸分布更为均一.     

聚乙烯亚胺交联壳聚糖微球的研制

交联壳聚糖(CLC)因有良好的耐酸性,对金属离子有极强的螯合能力,可用作含金属离子污水的吸附剂,已受到人们的广泛关注。但交联壳聚糖因交联反应往往发生在活性较高、具有螯合能力的-NH2上,致使-NH2含量降低;同时-NH2上其它基团的加入增加了氮同金属离子配位的空间位阻,因此吸附性能大大降低。     

影响聚乙二醇-g-壳聚糖载药体系的一些因素北大核心CSCD

聚乙二醇-g-壳聚糖可以作为抗肿瘤药物、基因、多肽等多种生物大分子的载体,是一种优良的药物载体。聚乙二醇接枝壳聚糖可以改善壳聚糖的水溶性,保护聚乙二醇-g-壳聚糖纳米不被网状内皮系统(RES系统)识别和清除,促进纳米粒子在体内的长循环,将药物更有效地靶向目标组织。目前,聚乙二醇-g-壳聚糖作为药物载体在生物医药领域发挥着重要作用,本文就聚乙二醇-g-壳聚糖的特点,以及在机体的靶向性、缓释等提高药物疗效的关键因素做一论述。     

（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖/聚乙二醇互穿网络凝胶的制备及其释药作用

将壳聚糖改性为（2-羟基-3-丁氧基）丙基 羟丙基壳聚糖（2-H-3-B-P-HPCS）,并以（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖和聚乙二醇（PEG）为原料制备（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖/聚乙二醇互穿网络凝胶,研究了（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖浓度、聚乙二醇的用量、交联剂戊二醛用量、反应温度对该凝胶溶胀性能的影响。 通过红外光谱分析和扫描电子显微镜的方法比较了壳聚糖、（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖和（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖/聚乙二醇互穿网络凝胶结构和形态上的不同。 以阿昔洛韦为模型药物研究了其释药性能。 结果表明,该凝胶均具有良好的溶胀性、pH敏感性和药物缓释作用,有望用作新型的药物载体。     

乳糖接枝聚乙烯亚胺壳聚糖的合成

本文通过马来酸酐化的壳聚糖,在2-NH2上引进分子量为2000的支链型聚乙烯亚胺,再用乳糖与聚乙烯亚胺的氨基反应,得到了乳糖接枝的聚乙烯亚胺化的壳聚糖。目标产物用1H NMR进行了表征。该共聚物在水中有很好的溶解性。     

亲核取代法制备壳聚糖6-OH固载环糊精衍生物

通过苯甲醛对壳聚糖2-NH2希夫碱化保护后,将壳聚糖C6位—OH与对甲苯磺酰氯反应形成对甲苯磺酰酯;然后用β-环糊精(-βCD)的单—NH2取代衍生物与之发生亲核取代反应,将环糊精固载到壳聚糖分子链上;最后,将得到的固载产物中的希夫碱脱保护后得到壳聚糖6-OH定位固载环糊精衍生物.采用FTIR,13C-NMR,元素分析,UV等表征手段对各步产物的结构进行了表征.紫外光谱法测定表明,-βCD在壳聚糖分子链C6位上的固载率达到了170.81μmol.g-1,远高于文献报道的其它方法制得的固载产物.采用XRD对各步产物的结晶性能进行了研究.     

羧甲基壳聚糖-熊果酸纳米载药粒子的合成及性能研究

选择水溶性羧甲基壳聚糖(CMCS)-聚乙二醇(PEG)作为载药分子链,叶酸(FA)作为靶向分子,利用pH感应酯键连接药物分子熊果酸(UA),通过吸附自组装包裹10-羟基喜树碱(HCPT),合成了一种抗肿瘤叶酸-聚乙二醇-羧甲基壳聚糖-熊果酸/10-羟基喜树碱~1H-NMR及TEM表征FA-PEG-CMCS-UA/HCPT纳米药物粒子结构和形态。核磁共振谱表明,UA是以酯键连接CMCS,透射电镜图显示纳米粒子呈球形;UA和HCPT的载药量分别为(6.4±0.1)%和(14.1±0.2)%;在pH值为7.4和5.5且PBS缓冲液中体外药物释放达到330h时,UA的累积释放率分别为70.2%和85.1%,HCPT的累积释放率达到73.8%和86.6%。     

羧甲基壳聚糖-PEG双缩水甘油醚凝胶微球的制备与表征

羧甲基壳聚糖是壳聚糖-NH2或-OH被羧甲基取代后的一类衍生物,具有优良的生物相容性和生物可降解性,同时具有抗菌作用。作为生物医用材料应用的潜力巨大。制备羧甲基壳聚糖生物膜或凝胶时多以戊二醛为交联剂[1],但戊二醛有一定的细胞毒性[2-3],用作医用材料的制备时有一定的局限     

交联壳聚糖对钒(Ⅴ)吸附机理的XPS研究

本文用X射线光电子能谱(XPS)研究了交联壳聚糖对钒(Ⅴ)的吸附机理,在对比交联壳聚糖(CCTS)吸附钒(Ⅴ)前后的XPS谱中,可观察到CCTS的N1s和钒(Ⅴ)的Ⅴ2p3/2峰都有较大的化学位移,说明钒(Ⅴ)与交联壳聚糖的-NH。基团发生了配位反应,交联壳聚糖对钒(Ⅴ)的吸附主要是化学吸附。     

Synthesis and characterization of folic acid‐modified carboxymethyl chitosan‐ursolic acid targeted nano‐drug carrier for the delivery of ursolic acid and 10‐hydroxycamptothecin

Carboxymethyl chitosan (CMCS), as a water‐soluble, biocompatible, and biodegradable polymer, is an excellent carrier for a sustained drug delivery system. In this study, a amphiphilic carboxymethyl chitosan‐ursolic acid nano‐drug carrier modified by folic acid (FPCU) were prepared, and then the nano‐drug carrier wrapped another anticancer drug 10‐hydroxycamptothecin were self‐assembled into nanoparticles (FPCU/HCPT NPs). The FPCU/HCPT NPs had a suitable size, high drug loading efficiency of ursolic acid (6.4%) and 10‐hydroxycamptothecin (14.1%). The drug release study in vitro indicated that the nanoparticles have obviously sustained effect and pH sensitive behaviors, the drug release amount was higher at pH 5.5 than at pH 7.4. in vitro and in vivo study showed that the nanoparticles displayed a high antitumor efficiency to tumor cells compared with free drug. The nano delivery system as a carrier for ursolic acid (UA) and 10‐hydroxycamptothecin (HCPT) has good application prospects in cancer treatment.     

Synthesis and Characterization of Chitosan-g-poly- （D, L-lactic acid） Copolymer

Biodegradable chitosan-g-poly (D, L-lactic acid) copolymers were prepared via two methods. (1) The lactide was grafted onto hydroxyl groups of chitosan by using macromolecular initiator sodium of trimethylsilyl-chitosan, (2) poly (D,L-lactic acid)(PLA) with low molecular weight can be linked to the amino group by coupling activated PLA to trimethylsilyl-chitosan. Two graft copolymers had hydrophilic-hydrophobic character and can be applied as carriers for drug delivery.     

An efficient mixed solid-liquid phase synthesis of a heterobifunctional amphiphilic PEG-NH2 derivative and its conjugation to folic acid

A very efficient, versatile as well as simple to perform procedure was developed in order to prepare a heterobifunctional amphiphilic PEG-NH₂ derivative which can be used for conjugation to a targeting ligand (such as folic acid). This method proceeds by a mixed solid-liquid phase strategy using a TentaGel^® PAP resin, a copolymer consisting of a polystyrene matrix on which a PEG (M_w 3400 Da) terminated by an amino function has been grafted. Solid phase chemistry was used for the conjugation of a highly hydrophobic moiety. After release from the resin, the amphiphilic PEG-OH conjugate was converted into its corresponding amphiphilic PEG-NH₂ derivative (four steps in 77% overall yields). This procedure allowed the preparation of ∼330 mg batches. This derivative was then coupled to folic acid, a ligand that is used for the targeting of drug (gene) carrier and delivery systems to cells over-expressing the folate receptor. The low and high molecular weight of folic acid and its amphiphilic PEG-folate conjugate, respectively, allowed easy purification by dialysis and led to the targeted compound with high recovery.     

LYOTROPIC LIQUID CRYSTALLINE BEHAVIOR OF FIVE CHITOSAN DERIVATIVES*

Five chitosan derivatives, i.e. O-butyryl chitosan, O-benzoyl chitosan, N-phthaloyl chitosan, N-maleoyl chitosan and O-cyanoethyl chitosan, were prepared from chitosan. All of them had better solubilitythan chitosan, and demonstrated lyotropic liquid crystalline behavior in various solvents. The critical liquidcrystalline behavior of three O-substituted chitosan derivatives was evidently different from two N-substituted analogues. Typical fingerprint textures of cholesteric phase were only observed in three O-substituted derivatives. The critical concentration (v/v%) of three O-substituted derivatives does not dependon the acidity of acidic solvents.     

3-Diethylaminopropyl-bearing glycol chitosan as a protein drug carrier

Polysaccharidic nanogels were fabricated with bovine serum albumin (BSA) and a glycol chitosan (GCS) grafted with functional 3-diethylaminopropyl (DEAP) groups. These nanogels were investigated to evaluate their cellular uptake in HeLa cells and in vivo fate in nude mice tumor model. Unlike free BSA, GCS-g-DEAP/BSA nanogels improved cellular uptake of BSA. Furthermore, this system led to an enhanced blood circulation and a high accumulation of BSA in the tumor site. Our collective results strongly support that GCS-g-DEAP/BSA nanogel is a potential carrier system for high molecular weight proteins.     

Preparation and characterization of m PEG grafted chitosan micelles as 5-fluorouracil carriers for effective anti-tumor activity

The objective of this study was to investigate the potential of methoxy polyethylene glycol（m PEG）grafted chitosan（m PEG-g-CS） to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method with formaldehyde. The substitution degree of m PEG on chitosan was calculated by elemental analysis and was found to be（3.23 0.25）%. m PEG-g-CS self-assembled micelles were prepared by ultrasonic method with the controlled size of 178.5–195.1 nm and spherical morphology. Stable dispersion of the micelles was formed with the zeta potential of 2.3–30.2 m V. 5-Fluorouracil（5-FU）, an anticancer chemotherapy drug, was used as a model drug to evaluate the efficiency of the new drug delivery carrier. The loading efficiency of 5-FU was（4.01 0.03）%, and the drug-loaded m PEG-g-CS self-assembled micelle showed a controlled-release effect. In summary, the m PEG-g-CS self-assembled micelle is proved to be a promising carrier with controlled particle size and controlled-release effect. Therefore, it has great potential for the application as 5-FU carriers for effective anti-tumor activity.     

Selective crystallization of calcium salts by poly(acrylate)-grafted chitosan

The biopolymer chitosan was chemically modified by grafting polyacrylamide or polyacrylic acid in a homogeneous aqueous phase using potassium persulfate (KPS) as redox initiator system in the presence of N,N-methylene-bis-acrylamide as a crosslinking agent. The influence of the grafted chitosan on calcium salts crystallization in vitro was studied using the sitting-drop method. By using polyacrylamide grafted chitosan as substrate, rosette-like CaSO4 crystals were observed. This was originated by the presence of sulfate coming from the initiator KPS. By comparing crystallization on pure chitosan and on grafted chitosan, a dramatic influence of the grafted polymer on the crystalline habit of both salts was observed. Substrates prepared by combining sulfate with chitosan or sulfate with polyacrylamide did not produce similar CaSO4 morphologies. Moreover, small spheres or donut-shaped CaCO3 crystals on polyacrylic acid grafted chitosan were generated. The particular morphology of CaCO3 crystals depends also on other synthetic parameters such as the molecular weight of the chitosan sample and the KPS concentration.     

Synthesis and spectroscopic and electrochemical studies of chitosan Schiff base derivatives

Schiff derivatives were prepared by the reactions of salicylaldehyde and its derivatives (5-chloro, 5-methoxy, 5-fluoro, 5-methyl, 5-nitro) with the amino group of chitosan. The Schiff bases were studied by Fourier IR spectroscopy and by UV-visible spectroscopy. The cyclic voltammograms of the Schiff bases were analyzed and compared to those of chitosan and salicylaldehyde. The formal potential of the chitosan Schiff base derivative correlates with the Hammett parameters. The oxidation potential increases and the optical density decreases with enhancement of the electron-acceptor properties of the functional group R in the m-position to the -N=CH-group. Chitosan (Chi) is a polysaccharide whose chains consist of recurrent units of acetamido-2-deoxy-D-glucode linked by the 1,4-β-glycoside bond. This polysaccharide was widely studied as drug carrier [1, 2], because it is nontoxic, biodegradable, and well biocompatible [3].