自修复氧化海藻酸钠-羧甲基壳聚糖水凝胶的制备及药物缓释性能

本研究基于动态亚胺键合成了一种具有自修复性能的氧化海藻酸钠-羧甲基壳聚糖水凝胶(OSA-CMCS).通过海藻酸钠的糖醛酸,合成了OSA,并通过与CMCS的席夫碱反应制备了具有不同交联度的自修复OSA-CMCS水凝胶,研究了OSA-CMCS水凝胶的微观形态、黏弹性能、溶胀性能、自修复性能、酶促降解性能和体外药物释放性能....     

Controlled release of heparin from blended polyurethane and silk fibroin film

Polyurethane was blended with silk fibroin and heparin to prepare a heparin-releasing system. The release rate and the percentage of the cumulative amount of the released heparin can be controlled by the loading amount of heparin in the film, the composition ratio of silk fibroin to polyurethane, and the thickness of the film. The slower and more sustained release of heparin can be obtained by increasing the film thickness, the loading amount of heparin and the content of silk fibroin in the film. Thus the high bioactivity and long lasting antithrombogenicity of the raw heparin can be maintained for the blended film. The coagulation time tests showed that the composite film had good blood compatibility.     

以电纺丝蛋白纤维为模板的pH响应性介孔SiO2纳米管的制备及药物释放

以资源丰富的家蚕丝为原料,氯化钙/甲酸为溶解体系,利用静电纺丝法制得丝素蛋白（SF）纳米纤维;以SF纤维为模板在其表面涂覆SiO₂,经煅烧后获得了介孔SiO₂纳米管（MSNTs）;在MSNTs管壁上接枝醛基（-CHO）,利用醛基与盐酸阿霉素（DOXHCl）氨基之间的动态共价键制得了pH响应性药物释放体系。通过SEM、TEM、TG、比表面积（BET）分析、FTIR及紫外-可见吸收（UV-Vis）光谱对MSNTs的微观结构、功能化及载药体系的pH响应性进行了表征。结果表明:当SF浓度在15wt%~17wt%时,可获得圆柱状且直径在（113±27）~（134±32）nm范围内可调的SF纤维模板;通过调整涂覆液中十六烷基三甲基溴化铵（CTAB）的浓度来调节MSNTs管壁的厚度,当CTAB用量从1.25 mg/mL增加到3.75 mg/mL时,MSNTs管壁厚度从30~39 nm增加到63~65 nm,对应的比表面积从154 m2/g下降到98 m2/g,介孔平均孔径从12.5 nm下降到10.0 nm;醛基修饰的MSNTs载DOXHCl（MSNT-CHO-DOX）体系,在pH值分别为7.4、6.5和5.5的磷酸氢二钾-磷酸二氢钾（PB）缓冲溶液中进行释放,100 h时释药率分别达到23%、35%和75%,实现了MSNT-CHO-DOX载药体系的pH响应性释放。      

可注射原位凝胶的制备及性能表征

以聚琥珀酰亚胺(PSI)为原料,利用酰亚胺基开环反应,首先制备得到α,β-聚(N-羟乙基)-DL-天门冬酰胺(PHEA),再与丙烯酰氯反应,制备得到接枝丙烯酰胺基α,β-聚(N-羟乙基)-DL-天门冬酰胺(PHA).通过FT-IR、NMR对其结构进行了表征.这种大分子单体的溶液可在人体温度下发生原位的交联反应,形成凝胶.可通过改变接枝率、大分子单体浓度等因素控制凝胶化时间.当选用质量浓度为0.1g/mL的PHA1#(接枝率为19.6%)单体、交联剂质量浓度为4mg/mL、引发剂浓度为20mmol/L时,凝胶化时间为90s.该凝胶具有可注射性和疏松的大孔结构,并且凝胶化时间可控,在模拟体液中有轻微溶胀,是较理想的治疗干眼症注射式材料.     

Preparation and properties of calcium sulfate bone cement incorporated with silk fibroin and Sema3A-loaded chitosan microspheres

To search for new bioactive materials which can be used as the substitute of bone repairing and drug carriers, Sema3A-loaded chitosan microspheres (SLCM) and silk fibroin (SF) were mixed with calcium sulfate cement (CSC). SEM, particle size analysis and swelling rate determination were performed to study properties of the microspheres. The drug loading, encapsulation efficiency and drug release rate were determined by ELISA. Microspheres with different SLCM weight contents (0.5%, 1% and 5%) were prepared to determine which one has the strongest mechanical properties and the appropriate setting time. It was revealed that CSC/SF/0.5SLCM has satisfactory mechanical properties, and its in vitro biocompatibility was assessed by MTS. Chitosan microspheres (5--18 μm) were globular, the surface was smooth, and the swelling rate is (77.02±5.57)%. With this formula, the setting time was increased with the addition of SLCM in CSC/SF, and the cumulative drug release rate is 44.62% in 28 d. XRD results demonstrate that the main component is calcium sulfate. Also it was found that CSC/SF/0.5SLCM supports the growth of MC3T3 cells. Thus the preparation of CSC/SF/0.5SLCM was reliable, and the products had good structures, physical properties and biocompati-bility, appearing to be a promising bone substitute material.     

Surface sulfonation of silk fibroin film by plasma treatment and in vitro antithrombogenicity study

To improve the blood compatibility of Bombyx mori silk fibroin (SF) film, the film was modified by SO₂ gas plasma treatment, or by a two-step process including NH₃ gas plasma treatment and reaction with 1,3-propane sultone. XPS and ATR-FTIR were used to analyze the surface chemical elements. In vitro antithrombogenicity was determined by the method of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) tests. Percents of sulfur element on the surfaces of both modified SF films were 4.03% and 3.30%, respectively, while that of the control film was only 0.32%. Moreover, the antithrombogencity of treated films was increased remarkably due to surface sulfonation. The results implied a potential use of sulfonated SF for blood-contacting biomaterials.     

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system

Context: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.

Objective: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.

Materials and methods: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.

Results: LSH tablets exhibited dynamic swelling–deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.

Discussion: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.

Conclusions: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.     

同轴静电纺再生丝素/丝胶蛋白纤维的制备及其形态结构表征

模仿蚕丝的组成和结构,利用同轴静电纺丝法制备了以再生丝素蛋白（RSF）为＂芯＂、丝胶蛋白（SS）为＂皮＂的双组分静电纺纤维。通过扫描电镜和透射电镜研究了内层纺丝液流速（Qc）、电压（U）、接收距离（D）以及场强（E）等参数对同轴静电纺RSF/SS纤维形态结构的影响。研究结果表明纤维的平均直径在1400～2100nm左右,皮-芯层结构清晰;Qc对纤维皮-芯层结构的影响较大,过大的内层纺丝液流速会因外层丝胶对内层丝素的包裹不均匀而导致偏芯现象;随E的增加（U增加或D减小）,纤维的直径及其分布显著减小,皮-芯层结构清晰;相同E下,高电压、长距离利于纤维的细化,使直径变细且分布均匀,皮-芯层结构明显。     

双氯灭痛壳聚糖水凝胶微球的制备及其性能研究

在Span80与植物油形成的反相胶束体系中,通过戊二醛交联制备出壳聚糖水凝胶微球(CHM)。采用红外光谱和透射电镜等方法对CHM结构及粒子形态进行了研究。同时对CHM的溶胀度及其对模型药物双氯灭痛的体外释放行为进行了考察。结果表明,CHM具有较好的控制药物释放的作用。交联程度对微球粒径、溶胀度及药物释放性能影响较大。     

Small-diameter vascular grafts of Bombyx mori silk fibroin prepared by a combination of electrospinning and sponge coating

The present study aimed to produce small-diameter grafts made of a silk fibroin by electrospinning. In order to reinforce the electrospun silk fibroin graft (ES), the graft was coated with a silk sponge (ESSC). Physical properties such as a diameter of the electrospun silk fibers were influenced by a concentration of fibroin solution. Ultimate tensile strength (UTS) of the ESSC graft was improved compared to the ES graft. However, the ESSC graft was less compliant than the ES graft. Importantly, water permeability of the ESSC graft was within the range of which endothelialization was promoted in previous studies.     

Preparation and cytocompatibility of silk fibroin/chitosan scaffolds

One challenge in soft tissue engineering is to find an applicable scaffold, not only having suitable mechanical properties, porous structures, and biodegradable properties, but also being abundant in active groups and having good biocompatibility. In this study, a three-dimensional silk fibroin/chitosan (SFCS) scaffold was successfully prepared with interconnected porous structure, excellent hydrophilicity, and proper mechanical properties. Compared with polylactic glycolic acid (PLGA) scaffold, the SFCS scaffold further facilitated the growth of HepG2 cells (human hepatoma cell line). Keeping the good cytocompatibility and combining the advantages of both fibroin and chitosan, the SFCS scaffold should be a prominent candidate for soft tissue engineering, for example, liver.     

Preparation and cytocompatibility of silk fibroin / chitosan scaffolds

One challenge in soft tissue engineering is to find an applicable scaffold, not only having suitable mechanical properties, porous structures, and biodegradable properties, but also being abundant in active groups and having good biocompatibility. In this study, a three-dimensional silk fibroin/chitosan (SFCS) scaffold was successfully prepared with interconnected porous structure, excellent hydrophilicity, and proper mechanical properties. Compared with polylactic glycolic acid (PLGA) scaffold, the SFCS scaffold further facilitated the growth of HepG2 cells (human hepatoma cell line). Keeping the good cytocompatibility and combining the advantages of both fibroin and chitosan, the SFCS scaffold should be a prominent candidate for soft tissue engineering, for example, liver.     

Evaluation of dibutyrylchitin as new excipient for sustained drug release

Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and ¹H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.     

Genipin交联丝素蛋白纳米纤维膜的制备与性能

利用Genipin对再生丝素蛋白进行交联改性, 并通过静电纺丝法制备交联的丝素蛋白纳米纤维膜。利用场发射扫描电镜、 红外光谱仪、 X射线衍射仪、 热重分析仪以及拉力机等对其结构与性能进行表征与测试。结果表明, 随着交联剂Genipin质量比的增加, 交联度增加, 静电纺丝素蛋白纳米纤维平均直径增大, 标准偏差增大;Genipin交联对丝素蛋白纳米纤维结晶结构影响不大, 但热性能提高;常温条件下, 随着Genipin质量比从2%提高至15%, 丝素蛋白纳米纤维膜的力学性能逐渐增强, 质量比为10%时, 其力学性能较好, 拉伸强度和断裂应变分别为19.6 MPa和5.9%;随着试验温度从40 ℃升高到200 ℃, 丝素蛋白纳米纤维膜的拉伸强度和断裂应变先增大然后减小, 当试验温度为80 ℃时, 其力学性能较好, 拉伸强度和断裂应变分别为41.6 MPa和8.6%。     

Preparation and characterization of amphotericin B-loaded silk fibroin nanoparticles-in situ hydrogel composites for topical ophthalmic application

Journal of Materials Science - The objective of this study was to develop and characterize a novel combined systems of amphotericin B-loaded silk fibroin nanoparticles (AmB-FNPs) and in situ...     

己酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶的制备及其药物缓释性能

为减少泊洛沙姆水凝胶的溶胶-凝胶转变温度对浓度的依赖性,以泊洛沙姆(P₄₀₇)为基材,将己酰化乙二醇壳聚糖(HGC)与泊洛沙姆复合,制备了己酰化乙二醇壳聚糖/泊洛沙姆(HGC/P₄₀₇)复合水凝胶,利用FTIR、SEM及试管反转法探讨了HGC/P₄₀₇复合水凝胶的性能,并利用紫外-可见分光光度计(UV-vis)对HGC/P₄₀₇复合水凝胶的体外药物缓释性能进行表征。结果表明,通过控制HGC的加入量,基于3%泊洛沙姆的HGC/P₄₀₇复合水凝胶即可发生溶胶-凝胶转变现象,并使HGC/P₄₀₇复合水凝胶的溶胶-凝胶转变温度处于32~37℃。HGC/P₄₀₇复合水凝胶具有高度孔隙率,孔隙之间相互连通,孔径大小处于10~90μm的范围之内。HGC/P₄₀₇复合水凝胶对抗癌药物吉西他滨的释药量达到82.4%~90.6%,缓释时间可达80 h左右。HGC/P₄₀₇复合水凝胶在可注射药物载体领域具有重要的应用前景。     

纳米羟基磷灰石/丝素蛋白/聚己内酯复合超细纤维的制备及表征

通过静电纺丝法制备出纳米羟基磷灰石/丝素蛋白/聚己内酯复合超细纤维,利用扫描电镜、红外光谱仪、X射线衍射仪对纳米羟基磷灰石/丝素蛋白/聚己内酯复合超细纤维形貌和结构进行表征,并进行了拉伸测试。结果表明,随着超细纤维中羟基磷灰石含量的增加,纤维的直径逐渐降低,纤维中聚己内酯的结晶逐渐变差。相比于丝素蛋白/聚己内酯超细纤维,含有质量比为30%羟基磷灰石的复合超细纤维仍具有较好的力学性能。体外小鼠成纤维细胞(L929)培养表明,纳米羟基磷灰石/丝素蛋白/聚己内酯复合超细纤维对细胞没有毒性。     

Fabrication and characterization of fibroin solution and nanoparticle from silk fibers of Bombyx mori

The present investigation aims to study the effect of degumming time on the structural property of silk fiber obtained by silk cocoons of Bombyx mori, followed by preparation of the regenerated silk fibroin (RSF) solution which can be subsequently molded into silk nanoparticles. Silk fibers degummed with different media at different time intervals were investigated for the degumming loss and were characterized using Ffourier transform infrared (FTIR), differential scanning calorimetry (DSC), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Maximum degumming was observed when the fibers were treated with sodium carbonate for 60 min. SEM and atomic force microscopy (AFM) images of RSF solution showed aggregation of silk globules resulting in formation of solvated macrochains and giving it an appearance of island-like morphology. Blank silk nanoparticles prepared from the RSF solution showed a smooth and spherical surface devoid of any adhesion using SEM, AFM, and transmission electron microscopy (TEM). The prepared silk nanoparticles may further be explored for loading drug entities and targeting.     

Spray-dried O-carboxymethyl chitosan as potential hydrophilic matrix tablet for sustained release of drug

Objective: The aim of the present investigation was to evaluate the use of spray-dried O-carboxymethyl chitosan (OCMCS) as potential hydrophilic matrix excipient for sustained release of drug.

Methods: The polymer was synthesized from chitosan, then spray-dried and characterized. Tablets with different OCMCS concentrations (80, 50, 30, 5 and 2% w/w), containing diltiazem (DTZ) as model drug, were prepared for direct compression (DC) and after the wet granulation method (WG).

Results: The spray-dried OCMCS powder was spherical, with a smooth surface and an average size of 2.2?µm. The tablets prepared for WG disintegrated in time less than 30?min. The tablets obtained for DC presented high retention of the drug, with zero order or Higuchi release kinetic. There was a direct relationship between the OCMCS concentration and the release ratio, swelling degree and water uptake behavior. DC tablets containing 80% OCMCS presented behavior as an effective swelling-control system. The DC tablets with 5% OCMCS showed a similar release profile at formulations with 30% HPMC.

Conclusion: Spray-dried OCMCS showed great potential as hydrophilic matrices for drug-sustained release.     

Optical and photocatalytic properties of sulfide semiconductor quantum dots (QDs) synthesized by silk fibroin template

Bio-template method is a simple, controllable and environmental friendly strategy to synthesize nanomaterials. It also avails the formation of bioactive and biocompatible nanoparticle–biomolecule hybrid for biotechnical applications. In this paper, silk fibroin was first successfully used as biomolecule template for the biomimic synthesis of CdS and ZnS quantum dots (QDs). The QDs showed promising applications as fluorescence probes and nanocatalysts. The effect of preparation situation to their optical and photocatalytic properties was well researched and CdS QDs with satisfying catalytic activities could be achieved by adjusting the protein matrix. It offers us a low-cost and effective way to synthesize series of sulfide semiconductor nanomaterials using silk fibroin.