壳聚糖微球及壳聚糖-明胶复合物微球的制备及缓释性能研究

采用乳化-化学交联法制备壳聚糖微球及壳聚糖-明胶复合物微球,并通过实验确定了最佳的成球条件:即m(壳聚糖)∶m(明胶)=2∶1 span-80用量为10g/100 mL,乳化剪切速度为600 r/min,交联率为60％,固化时间为40min.该方法制备的壳聚糖微球球形圆滑,粘连度小,亲水性好.此外在对壳聚糖药物缓释的研究基础上,对壳聚糖复合明胶后,对药物缓释的影响情况进行了研究探索.以生物可降解性和生物相容性好的壳聚糖和明胶为载体承载阿司匹林,研制出阿司匹林壳聚糖-明胶微球,为阿司匹林提供了一种理想的缓释载体.     

吡虫啉/羧甲基壳聚糖凝胶球的制备及释放性能

以羧甲基壳聚糖为载体材料,吡虫啉为模型药物,采用双组分交联剂的悬浮交联法制备了吡虫啉/羧甲基壳聚糖凝胶球,采用扫描电镜和红外光谱对凝胶球进行了表征,探讨了制备工艺条件对凝胶球性能影响,利用体外释放实验测定了交联羧甲基壳聚糖凝胶球的释放特性。研究表明,采用氯化钙-戊二醛双组分交联剂可获得外形规整而表面带有皱褶的载药凝胶球;交联凝胶球中吡虫啉与羧甲基壳聚糖间无化学键合;交联凝胶球的载药量和包封率随交联时间和氯化钙浓度的增加呈先升后降趋势,随戊二醛体积分数的增加呈显著下降趋势;吡虫啉释放速度,随交联剂中氯化钙浓度和戊二醛体积分数的增加呈先降后增趋势;随交联时间变化不显著。在较佳条件下可制备载药量为25.71%的吡虫啉/羧甲基壳聚糖凝胶球,控释时间可达6 d;释放机理初步确定为Super CaseⅡ型传递机理。     

竹叶黄酮壳聚糖缓释微球的制备及其性能研究

以壳聚糖为载体材料,戊二醛为交联剂,竹叶黄酮作为模型药物,采用乳化交联法,制备了载竹叶黄酮壳聚糖缓释微球。研究了载药比对微球的形貌、药物收率、包埋率和载药量的影响。结果表明:竹叶黄酮-壳聚糖微球呈规则球形,粒径10~50μm;竹叶黄酮经壳聚糖加载后,其释放时间长,释药均匀,具有良好的缓释性能。     

壳聚糖止血微球的制备优化及表征

以壳聚糖为原料,采用乳化交联技术制备壳聚糖止血微球。在单因素实验结果的基础上,采用响应面法优化壳聚糖止血微球的制备条件,通过体外凝血法对其止血活性进行评价。结果表明,最优制备工艺条件为:壳聚糖浓度1.4%,壳聚糖分子量600 k Da和戊二醛与壳聚糖质量比1∶1。在此条件下,微球平均溶胀率为346.56%,与理论预测相当吻合;止血微球具有良好的外观形貌,分散性好;红外分析表明,壳聚糖止血微球已经成功地进行了化学交联,具有稳定的空间结构;壳聚糖微球具有显著的促凝血活性,呈现剂量相关性。将为开发新型壳聚糖高效止血材料奠定基础。     

壳聚糖止血微球的制备优化及表征

以壳聚糖为原料,采用乳化交联技术制备壳聚糖止血微球。在单因素实验结果的基础上,采用响应面法优化壳聚糖止血微球的制备条件,通过体外凝血法对其止血活性进行评价。结果表明,最优制备工艺条件为:壳聚糖浓度1.4%,壳聚糖分子量600 k Da和戊二醛与壳聚糖质量比1∶1。在此条件下,微球平均溶胀率为346.56%,与理论预测相当吻合;止血微球具有良好的外观形貌,分散性好;红外分析表明,壳聚糖止血微球已经成功地进行了化学交联,具有稳定的空间结构;壳聚糖微球具有显著的促凝血活性,呈现剂量相关性。将为开发新型壳聚糖高效止血材料奠定基础。     

交联壳聚糖微球对喹乙醇吸附性能的研究

以壳聚糖为原料,乙酸乙酯为致孔剂,环氧氯丙烷为交联剂,通过交联法制备出改性壳聚糖,考察了交联壳聚糖微球对喹乙醇吸附的影响。结果表明,V(壳聚糖)∶V(乙酸乙酯)∶V(环氧氯丙烷)=30∶1∶1时,制备的交联壳聚糖微球对喹乙醇吸附性能较好;红外光谱表明,环氧氯丙烷与壳聚糖发生反应;扫描电镜分析验证环氧氯丙烷用量对交联壳聚糖微球吸附性能有一定影响;吸附动力学曲线得知交联壳聚糖微球在3 h对喹乙醇吸附达到平衡,有较好的吸附速度;与类似物(喹烯酮和乙酰甲喹)吸附特性比较得知,交联壳聚糖微球对喹乙醇有较好的选择吸附性。     

壳聚糖聚乙烯醇复合载药微球的制备

以壳聚糖(CS)为基质,通过聚乙烯醇(PVA)的引入制备壳聚糖聚乙烯醇复合载体可以分别采用室温和高温酸催化反应两种方法制备出释药性能和结构形态不同的两种复合载药微球Ⅰ和Ⅱ。其中壳聚糖/聚乙烯醇复合载药微球Ⅰ的制备工艺是调节壳聚糖和聚乙烯醇质量比6/5,复合微球Ⅰ的平均粒径1～20μm,载药量13%,LVFX体外12h累积释放80%。而壳聚糖/聚乙烯醇复合载药微球Ⅱ的平均粒径1.69μm,载药量17.1%,LVFX体外6hr基本完全释放。     

离子交联法制备负载布洛芬的壳聚糖微球

以壳聚糖为药用载体,焦磷酸钠(TSPP)为离子交联剂,布洛芬为模型药物,采用离子交联法制备壳聚糖微球制剂,考察处方和工艺因素对载药微球的包封率和载药量的影响;采用扫描电子显微镜和红外光谱对微球结构进行表征。实验结果表明:在pH=3.68的壳聚糖溶液中,正负电荷摩尔比20∶1,转速为325r/min,投药量为0.05g是较理想的壳聚糖微球制备条件。而交联剂滴加时间在20～60min之间对微球的载药量和包封率的影响不大。     

甲磺酸沙喹那韦三甲基壳聚糖微球的制备

为了提高甲磺酸沙喹那韦的生物利用度,制备了甲磺酸沙喹那韦三甲基壳聚糖微球并考察其体外溶出度。用喷雾干燥法制备甲磺酸沙喹那韦三甲基壳聚糖微球,用红外光谱进行鉴定,采用PBS7.4缓冲液和0.1 mol/L盐酸溶液考察微球的体外药物释放速率,用HPLC法检测药物浓度。结果显示,制备得到的甲磺酸沙喹那韦三甲基壳聚糖微球在体外近中性及酸性条件下能够持续释放,无突释现象。甲磺酸沙喹那韦三甲基壳聚糖微球有利于口服给药后,药物的持续释放。     

羧甲基壳聚糖离子配位微球的制备及性能研究

以羧甲基壳聚糖(CMCHS)为主要原料,采用静电脉冲液滴发生器制备羧甲基壳聚糖离子配位微球。光学显微镜观察微球具备规整形貌,扫描电镜分析显示干球粒径约为100μm且表面呈多孔结构;红外光谱证明其内部具有由CMCHS上的羧酸根与Ca^2 配位形成的羧酸盐结构。溶胀实验表明,CMCHS溶液浓度、金属离子种类及其浓度等制备条件均影响微球的溶胀性能．且其溶胀行为对pH值较敏感。药物体外释放初步研究表明,CaCl2浓度和释放介质pH值均对微球的释放性能产生影响。研究对其进一步应用于药物释放等领域具有重要意义。     

盐酸小檗碱壳聚糖缓释微球

采用乳化交联法,合成盐酸小檗碱壳聚糖缓释微球。运用简单比较法,找出影响盐酸小檗碱壳聚糖缓释微球外观形态以及载药率的主要因素。再运用正交实验法,得出当制备条件为:50mL乙酸乙酯,20mL 1.5%的壳聚糖醋酸溶液,0.16g盐酸小檗碱,3mL Span-80,5mL 50%戊二醛时,能得到载药率达最大值为26.39%的盐酸小檗碱壳聚糖缓释微球。     

T型微通道装置制备尺寸均一壳聚糖微球

采用T型微通道装置制备尺寸均一的壳聚糖微球. 研究了乳化剂用量、油水两相流速比和流速等条件对乳液粒径的影响,尝试制备了不同分子量的壳聚糖乳液,并确定了交联固化方式. T型微通道装置的油相通道直径350 mm,水相通道直径65 mm,两通道接口处直径16 mm. 以1.5%(w)的壳聚糖醋酸水溶液为水相,以液体石蜡/石油醚(7/5, j)的混合物作为油相,水相流速20 mL/min,油水两相流速比为15:1,4%(w)的PO-500作为油相乳化剂,制备得到的壳聚糖乳液粒径分布系数<10%. 以戊二醛的甲苯溶液作为交联剂,当戊二醛所含醛基与壳聚糖所含氨基的摩尔比为1:1时,交联时间选择2 h.     

Investigation on Conjugation Capacity of New Chitosan Carriers Based on Conjugated Model Toward Enzyme Delivery

In this work, for the first time, the authors report their observations on cross-linking condition, and its effects on conjugation capacity of a bioactive model. Therefore, carriers of chitosan films and microspheres were produced by using glutaraldehyde as bifunctional cross-linking agent. The following stages were carried out: preparation of cross-linked chitosan films and microspheres, conjugation of drug model on films and microspheres, investigation on the properties of the synthesized carriers and finally enzyme immobilization studies. Based on our results, degree of cross-linking and drug conjugation capacity, as two important factors, affect simultaneously the thermal, morphological, and hydrolytic behavior of the carriers in film and microsphere forms. From the experimental data, with increasing the degree of cross-linking and drug conjugation capacity, the drug release was increased up to 12% w/w of glutaraldehyde; however, on further increasing the degree of cross-linking (18% w/w), the drug released in a burst manner. Also, regarding to the results from drug and enzyme conjugates, it is possible to design diversity of the chitosan derivatives based on different degree of cross-linking as well as enzyme conjugation capacity as reliable carriers.     

戊二醛与甲醛交联壳聚糖微球的比较研究

壳聚糖微球是肥料和农药的重要缓释载体之一。根据相关实验数据及文献显示,纯的壳聚糖成球性能差,易溶解,需要加入一定的交联剂、乳化剂和致孔剂对其进行交联改性,改善微球的性能。分别采用戊二醛、甲醛两种交联剂,通过乳化-化学交联方法制备壳聚糖微球。通过扫描电子显微镜对壳聚糖微球表面、内部结构及形态特征进行观察,测量壳聚糖微球粒径的大小。采用红外光谱(FT-IR)以及交联度测试对两种交联微球进行了对比。结果表明:以戊二醛为交联剂所制得的壳聚糖微球各个方面性能均优于以甲醛为交联剂所制得的壳聚糖微球。     

Novel blend microspheres of poly(vinyl alcohol) and succinyl chitosan for controlled release of nifedipine

Water-soluble succinyl chitosan (SCS) was synthesized by reacting succinic anhydride with –OH and –NH₂ reactive groups of chitosan (CS). The blend hydrogel microspheres were prepared from SCS with poly(vinyl alcohol) (PVA) by water-in-oil (w/o) emulsion cross-linking using glutaraldehyde (GA) as the cross-linking agent. Nifedipine (NFD), an antihypertensive drug having a plasma half-life of 2 h, was encapsulated giving encapsulation efficiency up to 92 % and its release was extended up to 12 h. Scanning electron microscopy (SEM) confirmed the spherical nature and smooth surfaces of the microspheres, while Fourier transform infrared spectroscopy (FTIR) confirmed succinylation of CS and chemical stability of NFD in the matrix. Thermogravimetry (TGA) and differential scanning calorimetry (DSC) characterized the SCS and the blend hydrogel microspheres. X-ray diffraction (XRD) and DSC were also used to study the crystalline or amorphous nature of NFD. Swelling and in vitro release experiments performed in pH 1.2 and 7.4 buffer media showed a dependence of blend composition, extent of cross-linking and pH of the media. The mechanism of drug release as analyzed by an empirical equation, suggested non-Fickian trends.     

壳聚糖-琼胶复合微球的制备及其药物释放性能

采用小分子离子交联法制备了pH值敏感的壳聚糖-琼胶复合微球,对壳聚糖-琼胶复合微球的粒径、形貌、pH值敏感性等进行了表征.以茶碱为模型药物研究了壳聚糖-琼胶复合微球的药物释放性能,结果发现一定量琼胶的引入有助于改善壳聚糖微球的药物缓释性能.     

壳聚糖/聚丙烯酸共聚物微球的制备及性能

以环己烷为油相,壳聚糖溶液为水相,运用反相乳液聚合法制得了具有pH敏感性的壳聚糖/聚丙烯酸共聚物微球。讨论了微球在pH=1～10缓冲溶液中的溶胀率变化,研究表明,微球在强酸性(pH≈1)和碱性(pH>7)条件下,溶胀率均在10倍以上;而在pH=2～6时溶胀较差,当pH=4时出现最低值,溶胀率低于1倍。光学显微镜所观察到的微球粒径均在40μm以内,且大小均匀。采用傅里叶红外光谱仪分析了不同配比样品特征峰的峰值和峰面积的变化。用722光栅分光光度计研究了共聚物微球包埋考马斯亮蓝的溶胀释放过程。     

凹凸棒石黏土/壳聚糖复合树脂微球的制备与表征

以壳聚糖(chitosan,CS)和凹凸棒石粘土(attapulgite,ATP)为原料,运用乳化交联法制备了一种具有高吸附性能的凹凸棒石黏土/壳聚糖树脂微球(attapulgite/chitosan resinmicrospheres,ACRM),利用扫描电镜和Fourier变换红外光谱对微球形貌和结构进行了表征.考...     

Genipin-cross-linked silk fibroin microspheres prepared by the simple water-in-oil emulsion solvent diffusion method

This work describes for the first time the preparation of cross-linked and non-cross-linked silk fibroin (SF) microspheres using the simple water-in-oil emulsion solvent diffusion method. Aqueous SF solution and ethyl acetate were used as water and oil phases, respectively. Span80, oil-soluble emulsifier was found to induce the formation of SF microparticles that are completely spherical in shape and smooth in surface. SF microsphere sizes were found to depend upon various process parameters. The SF microsphere matrices showed predominantly random coil conformation. It was possible to fabricate genipin-cross-linked SF microspheres by cross-linking SF solution with genipin before microsphere formation. Both non-cross-linked and genipin-cross-linked SF microspheres contained porous structures. Percentage of dissolution in water decreased and density values of the SF microspheres increased when increasing the genipin ratio and cross-linking time. The genipin cross-linking induced SF conformational transition from random coil to β-sheet form but the size and shape of the SF microparticles did not change. It is suggested that these SF microspheres might be suitable microcarriers for hydrophilic drug delivery.     

Drug Release Kinetics of Spray-Dried Chitosan Microspheres

The aim of this article was to investigate the drug release kinetics of spray-dried chitosan microspheres using various kinetic models. The mean particle size and encapsulation efficiency of cross-linked chitosan microspheres was between 3.8 and 4.2 μm and 96.3 and 98.7%, respectively. Spray-dried chitosan microspheres were spherical in shape with smooth surface. The surface morphology of spray-dried chitosan microspheres was affected by the crystallinity of the loaded drug and cross-linking agent. The release data of the spray-dried chitosan microspheres were treated with zero-order, first-order, Higuchi, Korsmeyer, and Kopcha kinetic models and best fit was observed with Higuchi model, indicating the release of drug from spray-dried chitosan microspheres followed Fick's law of diffusion.