水溶性O-羟乙基壳聚糖接枝聚乳酸的制备与表征

目的制备用于组织工程的水溶性O-羟乙基壳聚糖／聚乳酸共聚物纤维复合支架。方法首先采用壳聚糖与环氧乙烷反应制备水溶性O-羟乙基壳聚糖,然后以辛酸亚锡为催化剂,水溶性O-羟乙基壳聚糖为引发剂,采用本体封管聚合法,激发D,L-丙交酯开环聚合制备水溶性O-羟乙基壳聚糖-g-聚乳酸共聚物。分别用X射线衍射、红外光谱、扫描电镜和溶解实验对产物的结构与性能进行分析表征。结果改性后的水溶性O-羟乙基壳聚糖能明显提高溶解性能,降低结晶性能和氢键间的相互作用。结论通过改性,为得到水溶性O-羟乙基壳聚糖／聚乳酸共聚物奠定了有利条件,并且此共聚物具有较好的孔隙率和网状结构,这对作为药物支架是一个很好的应用。此外,改性后的共聚物易溶于一些常用的有机溶剂中,有利于以后在组织工程中进一步应用。     

羧甲基壳聚糖-壳聚糖-羧甲基壳聚糖微胶囊的制备、表征及其对Pb2+的吸附性能研究

以壳聚糖和羧甲基壳聚糖为主要原料，利用静电脉冲液滴发生器制备了一种新型微胶囊——羧甲基壳聚糖-壳聚糖-羧甲基壳聚糖微胶囊(简称CCC微胶囊)。通过光学显微镜和红外光谱对其形貌和结构进行研究，同时考察了CCC微胶囊对金属离子的吸附性能。静态和动态吸附结果表明：CCC微胶囊对Pb^2 有很高的吸附能力，且重复使用性能良好。选择性吸附结果表明：其对Pb^2 的选择性要高于Ca^2 。为进一步实现以血液净化方法除铅的应用打下了良好基础。     

海藻酸钙/壳聚糖磁性微胶囊的制备及研究

采用高压静电法制备磁性海藻酸钙/壳聚糖微胶囊,Minitab全因子实验考察不同制备条件对微胶囊形貌、粒径分布及破损率的影响。以超氧化物歧化酶（SOD）为模型药物,考察磁性微胶囊的包封率、载药量及体外释放性能,并初步研究磁性微胶囊的靶向性。     

海藻酸钙/壳聚糖磁性微胶囊的制备及研究

采用高压静电法制备磁性海藻酸钙/壳聚糖微胶囊,Minitab全因子实验考察不同制备条件对微胶囊形貌、粒径分布及破损率的影响.以超氧化物歧化酶(SOD)为模型药物,考察磁性微胶囊的包封率、载药量及体外释放性能,并初步研究磁性微胶囊的靶向性.     

海藻酸钠-壳聚糖微胶囊载体在组织工程研究中的应用

背景：用壳聚糖包裹海藻酸钠制备微囊,可以改善海藻酸钠水凝胶的力学性能,如何获得理想的海藻酸钠壳聚糖微囊以及该微囊体系的应用前景是这一研究的关键。 目的：探讨海藻酸钠壳聚糖微胶囊载体的制备方法、成型机制,分析影响微胶囊膜强度性能的几个重要因素及探讨海藻酸钠-壳聚糖微胶囊在固定化细胞技术、药物载体和组织工程方面的应用前景。 方法：由第一作者采用计算机检索PubMed数据库、Elsevier ScienceDirect、中国知网库、万方数据库1987至2013年有关海藻酸钠壳聚糖微囊制备方法、反应机制及应用前景的文章。 结果与结论：海藻酸盐水凝胶在药物释放和组织工程领域具有很多优势,但是凝胶溶蚀现象和力学性能缺陷限制了它的应用,壳聚糖与海藻酸钠通过静电相互作用形成聚电解质络合物,弥补了海藻酸钠凝胶的不足。通过控制壳聚糖溶液的性质-壳聚糖的分子质量、壳聚糖溶液的pH值和浓度制备膜强度高的微囊,海藻酸钠-壳聚糖微囊在固定化技术、药物释放和组织工程领域表现出了广阔的应用前景。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

载间充质干细胞海藻酸钠-壳聚糖微胶囊的制备及工艺优化

目的：以壳聚糖为囊材来制备间充质干细胞（MSCs）海藻酸钠．壳聚糖体系微胶囊。方法：通过研究羧甲基壳聚糖、低聚壳聚糖等不同种类壳聚糖的成囊性，以及壳聚糖溶液浓度对间充质干细胞活性的影响，来优化微胶囊制备工艺。结果：羧甲基壳聚糖不能成膜；低聚壳聚糖成囊性差；高相对分子质量（尬）壳聚糖成囊性良好，但微囊粒径大且易破碎；Mr为100000～250000的壳聚糖具有良好的成囊性。结论：可用Mr100000～250000的壳聚糖来制备载MSCs海藻酸钠．壳聚糖微胶囊。同时应控制壳聚糖溶液覆膜时间〈10min，以及1g／L壳聚糖溶液来降低其对间充质干细胞活力的影响。     

壳聚糖水凝胶微球模板的载肝素层层自组装微胶囊

背景：近年来,对抗凝血药物肝素的控释一直存在争议,静电层层自组装是微胶囊载药简单有效的新方法。 目的：制备壳聚糖水凝胶微球模板的载肝素层层自组装微胶囊,从而实现对抗凝血药物肝素的控释。 方法：采用硫酸钠沉淀的方法制备了具有正电荷的壳聚糖微球模板,通过层层自组装的方法装载抗凝血药物肝素。壳聚糖(CS)作为聚阳离子和肝素(Heparin, Hep)作为聚阴离子,在壳聚糖微球的模板上层层自组装形成{CS/Hep}3。{CS/Hep}3包被壳聚糖微球模板的微胶囊通过倒置荧光显微镜、激光共聚焦显微镜和激光粒度分析进行了表征。壳聚糖和肝素的层层自组装过程通过Zeta电位分析进行监测。 结果与结论：{CS/Hep}3包被壳聚糖微球模板的微胶囊平均直径1 μm,包封率和载肝素量分别为83.8%和3.05%。成功制备了壳聚糖水凝胶微球模板的载肝素层层自组装微胶囊,进而实现对抗凝血药物肝素的控释。     

壳聚糖微球药物释放机制研究进展

近年来已有多种药物实现了以壳聚糖微球作为缓控释载体,并在生物医学领域展现出良好的应用前景,成为缓控释剂型研究的热点之一。目前对壳聚糖微球释放机制的研究进展落后于壳聚糖载药微球制备与应用的研究进展,而加强壳聚糖载药微球药物释放机制的研究,有利于更好地了解药物的释放行为和释放影响因素,并对深入研究壳聚糖缓释载药体系的制备与应用具有重要意义。主要从壳聚糖微球的药物释放机制、药物释放行为描述、药物释放影响因素等方面进行了综述。     

缓慢释放bFGF壳聚糖多孔支架的构建及对细胞生长的影响

采用冷冻干燥制备壳聚糖支架,以牛血清白蛋白（BSA）和碱性成纤维细胞生长因子（bFGF）为模型药物,制备乳酸-乙醇酸共聚物（PLGA）微球,并将其包埋于壳聚糖支架中,考察药物在支架上的体外释放。以MTT法考察了缓慢释放的bFGF对L929细胞的影响。用扫描电镜观察包埋微球支架的形态和生长了细胞的支架。结果表明单用壳聚糖支架,药物释放得比较快,制成PLGA微球后,再包埋于壳聚糖支架中,则药物释放明显缓慢。缓慢释放的bFGF促进了细胞的生长。     

壳聚糖膜及其改性膜的药物释放动力学研究

利用时间滞后（Lag-time）法,研究药物起始浓度（C0)、膜厚（h)和体系流动速度（v）对壳聚糖膜药物释放动力学参数的影响。结果表明：C0对滞后时间（T0)或扩散系数（D）没有影响;随h增大,T0增大,D值增大;随v增大,T0缩短,D值增大。还制备了N-烷基化壳聚糖膜。实验结果表明,在相同条件下,N-烷基化壳聚糖的T0值比纯壳聚糖膜的T0值小。     

Preparation of chitosan/ethylcellulose complex microcapsule and its application in controlled release of vitamin D2

A system which consists of chitosan (CS) microcores entrapped within enteric polymer is investigated. Vitamin D2 (VD2) used as a model drug, was efficiently entrapped in CS microcores using spray drying and was microencapsulated by coating of ethylcellulose. The morphology and release properties of microcapsules were tested. The factors which influenced the preparation, including molecular weight of CS, concentration of CS solution, concentration of acetic acid and loading of VD2, were discussed. The results of release in vitro showed that the microcapsules could realize sustained release in intestine juice.     

Gradient nanofibrous chitosan/poly ɛ-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering

One of the major challenges of tissue-engineered small-diameter blood vessels is restenosis caused by thrombopoiesis. The goal of this study was to develop a 3D gradient heparinized nanofibrous scaffold, aiding endothelial cells lined on the lumen of blood vessel to prevent thrombosis. The vertical graded chitosan/poly ?-caprolactone (CS/PCL) nanofibrous vessel scaffolds were fabricated with chitosan and PCL by sequential quantity grading co-electrospinning. To mimic the natural blood vessel microenvironment, we used heparinization and immobilization of vascular endothelial growth factor (VEGF) in the gradient CS/PCL. The quantity of heparinized chitosan nanofibers increased gradually from the tunica adventitia to the lumen surfaces in the gradient CS/PCL wall of tissue engineered vessel. More heparin reacted to chitosan nanofiber in gradient CS/PCL than in uniform CS/PCL nanofibrous scaffolds. Antithrombogenic properties of the scaffolds were enhanced by the heparinization of these scaffolds, as shown by activated partial thromboplastin time and platelet adhesion assay. Compared to the uniform CS/PCL scaffold, the release of VEGF from the gradient CS/PCL was more stable and sustained, and the burst release of VEGF was reduced approximately 42.5% within the initial 12 h. The adhesion and proliferation of human umbilical vein endothelial cells (HUVEC) were enhanced on the gradient CS/PCL scaffold. Furthermore, HUVEC grew and formed an entire monolayer on the top side of the gradient CS/PCL scaffold. Therefore, use of vertical gradient heparinized CS/PCL nanofibrous scaffolds could provide an approach to create small-diameter blood vessel grafts with innate properties of mammalian vessels of anticoagulation and rapid induction of re-endothelialization.     

Synthesis and characterization of chitosan-poly(acrylic acid) nanoparticles

Chitosan (CS)-poly(acrylic acid) (PAA) complex nanoparticles, which are well dispersed and stable in aqueous solution, have been prepared by template polymerization of acrylic acid (AA) in chitosan solution. The physicochemical properties of nanoparticles were investigated by using size exclusion chromatography, FT-IR, dynamic light scattering, transmission electron microscope and zeta potential. It was found that the molecular weight of PAA in nanoparticles increased with the increase of molecular weight of CS, indicating that the polymerization of acrylic acid in the chitosan solution was a template polymerization. It was also found that the prepared nanoparticles carried a positive charge and showed the size in the range from 50 to 400 nm. The surface structure and zeta potential of nanoparticles can be controlled by different preparation processes. The experiment of in vitro silk peptide (SP) release showed that these nanoparticles provided a continuous release of the entrapped SP for 10 days, and the release behavior was influenced by the pH value of the medium.     

The influence of spatial distribution on add-on therapy of designed Ca-Alg/CS MEMs system

To improve the efficacy and reduce the systemic toxicity of the diabetes mellitus, herewith, we developed a novel microparticles-embedded microcapsules (MEMs) system, synthesized from calcium alginate/chitosan (Ca-Alg/CS), by emulsion gelation using a high voltage electrostatic droplet generator. In our study, we selected two antidiabetic drugs insulin (INS) and metformin (MET) as model drugs to investigate different spatial distribution appropriate of MEMs system. Characterization based on particle size and morphology, encapsulation efficiency and drug loading, as well as drug delivery properties were carried out on the MEMs system. Typical multi-chamber structure was shown by SEM and the optical spectra. The average diameters of microparticles and Ca-Alg/CS MEMs were 2100 nm and 410 μm, respectively. Insulin and MET were embedded into MEMs via electrostatic reaction according to FT-IR spectra. Moreover, drug loading and encapsulation efficiency of INS were higher than that of MET in this system when drugs were loaded alone or together. More importantly, this system has potential for orderly drug release and well sustained release when MET in the inner and INS in the outer space could be applied as a combination therapy for diabetes. The obtained in vivo experimental data on diabetes rats has shown that the designed MEMs system resulted in a higher hypoglycemic effect within add-on therapy.     

The collagen-containing alginate/poly(L-lysine)/alginate microcapsules

A method of preparing microcapsules containing collagen fibrous network is reported in this study. This method takes advantage of miscibility of collagen and alginate and the ability of this mixture to form spherical gel beads in the presence of CaCl2. Collagen was then reconstituted within the microcapsules at 37 after alginate was liquefied with citrate. GH3 rat pituitary tumor cell, which can be cultured in both suspended and attached forms, were entrapped within the microcapsules. The cell proliferated faster in the collagen-containing capsule as compared to those in the conventional microcapsules.     

Chitosan microparticles for oral vaccination: preparation, characterization and preliminary in vivo uptake studies in murine Peyer's patches

Although oral vaccination has numerous advantages over parenteral injection, degradation of the vaccine in the gut and low uptake in the lymphoid tissue of the gastrointestinal tract still complicate the development of oral vaccines. In this study chitosan microparticles were prepared and characterized with respect to size, zeta potential, morphology and ovalbumin-loading and -release. Furthermore, the in vivo uptake of chitosan microparticles by murine Peyer's patches was studied using confocal laser scanning microscopy (CLSM). Chitosan microparticles were made according to a precipitation/coacervation method, which was found to be reproducible for different batches of chitosan. The chitosan microparticles were 4.3+/-0.7 microm in size and positively charged (20+/-1 mV). Since only microparticles smaller than 10 microm can be taken up by M-cells of Peyer's patches, these microparticles are suitable to serve as vaccination systems. CLSM visualization studies showed that the model antigen ovalbumin was entrapped within the chitosan microparticles and not only associated to their outer surface. These results were verified using field emission scanning electron microscopy, which demonstrated the porous structure of the chitosan microparticles, thus facilitating the entrapment of ovalbumin in the microparticles. Loading studies of the chitosan microparticles with the model compound ovalbumin resulted in loading capacities of about 40%. Subsequent release studies showed only a very low release of ovalbumin within 4 h and most of the ovalbumin (about 90%) remained entrapped in the microparticles. Because the prepared chitosan microparticles are biodegradable, this entrapped ovalbumin will be released after intracellular digestion in the Peyer's patches. Initial in vivo studies demonstrated that fluorescently labeled chitosan microparticles can be taken up by the epithelium of the murine Peyer's patches. Since uptake by Peyer's patches is an essential step in oral vaccination, these results show that the presently developed porous chitosan microparticles are a very promising vaccine delivery system.     

Entrapment of basic fibroblast growth factor (bFGF) in a succinylated chitosan nanoparticle delivery system and release profile

Basic fibroblast growth factor (bFGF) helps to regulate the proliferation and migration of fibroblasts, the proliferation of endothelial cells, and aids the development of angiogenesis. Its in vivo half-life is on the order of minutes due to extensive degradation and inactivation, which could be potentially reduced by controlled release vehicles. In this study, bFGF was entrapped into chitosan (CS) and N-succinyl-chitosan (SC) nanoparticles, with and without heparin, at two levels of initial loading, followed by further characterization of the particles. Release studies were conducted using radiolabeled bFGF-loaded nanoparticles. Both types of nanoparticles loaded similar amounts of bFGF (60.2 and 68.6% for CS and SC, respectively). The release profile varied greatly among the samples, and a burst release was observed in most cases, with the release amount approaching its final value in the first 6 h. The final amount released varied from 1.5 to 18% of the amount of bFGF-entrapped. The concomitant encapsulation of heparin and the use of SC as a nanoparticle matrix contributed to the largest amount of bFGF release (18%) over the time investigated.     

Novel protein-loaded chondroitin sulfate-chitosan nanoparticles: preparation and characterization

In this study, the potential of chondroitin sulfate (ChS)–chitosan (CS) nanoparticles (NPs) for the delivery of proteins was investigated. ChS–CS NPs were prepared by ionic cross-linking of CS solution with ChS. The aggregation line, particle size and zeta potential were investigated as a function of the pH, weight ratio and concentration. The water content and formation yield of the NPs were measured by gravimetry. Results indicated that ChS–CS NPs showed a higher degree of ionic cross-linking and formation yield than sodium tripolyphosphate–CS NPs. Fluorescein isothiocyanate conjugate bovine serum albumin (FITC–BSA), a model protein drug, was incorporated into the ChS–CS NPs. The encapsulation efficiency was obviously increased with the increase in initial FITC–BSA concentration and was as high as 90%. In vitro release studies of ChS–CS NPs showed a small burst effect following a continued and controlled release. Cytotoxicity tests with Caco-2 cells showed no toxic effects of ChS–CS NPs. The ex vivo cellular uptake studies using Caco-2 and HEK-293 cells indicated that NPs were found to be endocytosed into the cells. In conclusion, ChS–CS NPs are a potential new delivery system for the transport of hydrophilic compounds such as proteins.