海藻酸钠微囊栓塞治疗肾挫裂伤的实验研究

目的研究模拟野战条件下,在新型野战伤病综合手术救治方舱内应用海藻酸钠-壳聚糖微囊栓塞治疗肾挫裂伤的可行性。方法构建肾挫裂伤动物模型,在新型野战伤病综合手术救治方舱内,应用海藻酸钠-壳聚糖微囊对损伤的肾动脉血管进行栓塞模拟操作。观察栓塞后30min、1周的肾动脉造影检查结果,栓塞后1周的组织学表现,评价栓塞效果。结果 4只动物均存活,栓塞后血压波动于正常范围;血管造影检查与组织学表现显示,栓塞后30min栓塞侧肾动脉分支主干出现明显血栓影;栓塞后1周栓塞侧肾动脉完全闭塞;栓塞后1周健侧肾脏未发生任何变化,栓塞侧肾脏体积与重量减小,部分肾脏表面及剖面颜色变浅,剖面可见皮质变薄,皮质、髓质界限不清,髓放线模糊。结论新型野战伤病综合手术救治方舱,能满足野战条件下急重症伤员提供综合快速的诊治;海藻酸钠-壳聚糖微囊治疗肾挫裂伤疗效确切、直观、准确、便捷。     

流化床包衣法制备银耳多糖肠溶微粒

目的 考察并优化流化床包衣法制备银耳多糖肠溶微粒(ETPP)工艺条件.方法 以Eudragit L30-D55水分散体为包衣材料,柠檬酸三乙酯为增塑剂,滑石粉为抗黏剂,同时考察包衣后微粒的累计释放度,制备直径小于190 μm肠溶微粒.结果 载药量为40.62％,包封率为79.29％,酸中累计释放度小于10％,碱液中累计释放度大于75％,制备的微粒其平均粒径在115～190um之间,圆整度、堆密度、总收率均较理想.结论 应用流化床包衣法制备ETPP,其工艺简便,稳定可行,适合小鼠药物药理学和毒理学研究的需要和大工业生产.     

几丁糖预防术后肠粘连的临床对照观察

目的观察医用几丁糖预防术后肠粘连的效果。方法2004年9月～2006年2月共143例病人行剖腹手术,随机分成试验组和对照组,试验组(72例)应用医用几丁糖预防术后肠粘连,对照组(71例)术后直接关腹。结果试验组经过至少6个月的随访无1例发生肠粘连,对照组出现10例肠粘连症状,3例严重者出现粘连性肠梗阻。结论医用几丁糖是一种较理想的预防术后肠粘连的生物材料。     

壳聚糖-海藻酸盐纳米粒子的制备及其对BSA的载药与释放特性

带相反电荷的聚电解质在水溶液中能通过静电相互作用自组装形成壳聚糖-海藻酸盐纳米粒。利用动态光散射纳米粒度分析仪考察了钙离子及壳聚糖对粒子粒径的影响。结果表明：钙离子的存在可使粒子粒径从268．5nm降为203．4nm，但随着钙离子含量的继续升高，粒径迅速增大，当钙离子浓度大于0．45g／L时形成凝胶。壳聚糖含量的增加和蛋白的包裹均会使粒径增大。所制备的纳米粒对BSA具有较高的包栽能力，并有一定的缓释作用。当壳聚糖投料量增加时，可使BSA在pH=7．4的PBS中的释放减慢。     

骨髓间充质干细胞在壳聚糖凝胶中体外三维培养的实验研究

目的研究猪骨髓间充质干细胞在壳聚糖/β-甘油磷酸钠凝胶中体外三维培养的生长和增殖情况,探讨壳聚糖/β-甘油磷酸钠凝胶与骨髓间充质干细胞的细胞相容性。方法将间充质干细胞与壳聚糖/β-甘油磷酸钠凝胶混合,体外三维培养3周,采用倒置相差显微镜观察细胞在凝胶内粘附、生长和增殖等情况,复合物行组织形态学观察。结果间充质干细胞能良好地在壳聚糖/β-甘油磷酸钠凝胶内伸展、粘附、生长和增殖,细胞在新形成的组织内保持成活。结论壳聚糖/β-甘油磷酸钠凝胶与间充质干细胞具有良好的细胞相容性,可作为间充质干细胞的载体。     

胰岛素壳聚糖纳米粒的制备

 目的制备胰岛素壳聚糖纳米粒。方法采用酶水解和超滤膜分离技术，得到不同相对分子质量的壳聚糖，由凝胶渗透色谱法测定其相对分子质量；采用溶剂扩散法制备纳米粒，研究纳米粒的空间结构，测定其粒径、表面电位(zeta电位)、模型药物胰岛素包封率及体外释放。结果通过控制酶水解条件，经超滤分离得到3种不同相对分子质量的壳聚糖，凝胶渗透色谱法测得的重均相对分子质量(MW)分别为10 289，41500和101 870。经溶剂扩散法制备得到的壳聚糖纳米粒，呈类圆形球体，粒径分布较窄，且随制备工艺中乙醇加入量的增加、分散用超声次数的增多，以及壳聚糖分子量的降低，粒径变小。壳聚糖纳米粒带正电荷，zeta电位值大于+30 mV。放射免疫法测得的药物包封率为72.66%。在壳聚糖酶存在条件下，前1 h体外释放药物较快，1 h后趋于平稳，并能持续释放6 h。结论选用合适相对分子质量壳聚糖制备胰岛素壳聚糖纳米粒，方法简便，药物包封率高，并有一定的缓释作用。     

阿魏酸壳聚糖缓释微球的工艺优化及释药机制研究

 目的 优化离子凝聚法制备阿魏酸壳聚糖微球的工艺,并研究其缓释机制。方法 运用Doehlert设计、多重相应的渴求函数优化法对阿魏酸壳聚糖微球的工艺进行优化。通过显微镜观察和差示热分析研究微球结构和药物状态,探讨释药机制。结果 投药量和交联液pH值对包封率有很大影响。在优化条件下,阿魏酸壳聚糖微球的平均包封率为73.77％,平均载药量为8.08％,药物释放符合Higuchi方程和Weibull分布。药物以微晶状态分布于微球的骨架结构中,未与壳聚糖发生作用。结论 离子凝聚法制备的壳聚糖微球的缓释行为与其网状骨架结构相关。     

Formulation and evaluation of novel tableted chitosan microparticles for the controlled release of clozapine

Controlled release formulations of clozapine microparticulated tablets were prepared by using chitosan. Microparticles were characterized for particle size and size distribution. Microparticles were compressed into tablets using the directly compressible excipients. SEM photographs of the fractured part of the tablet revealed the presence of discrete particles in the tablets, suggesting that the system chosen is ideal for tableting. Drug release from the tableted microparticles exhibited an initial burst effect, but the release decreased with increasing extent of cross-linking. Tablets were coated with chitosan or cellulose acetate, which significantly lowered the initial burst effect when compared to uncoated tablets. Drug release from chitosan-coated tablets was slightly higher than the tablets coated with cellulose acetate. Tablets prepared were effective in delivering clozapine over a period of 12?h.     

DNA–chitosan nanoparticles improve DNA vaccine-elicited immunity against Newcastle disease virus through shuttling chicken interleukin-2 gene

In this study, pCAGG-ChIL2 plasmid DNA containing the chicken interleukin-2 (ChIL-2) gene was used to prepare DNA–chitosan nanoparticles (CNPs). The CNPs prepared were spherical, with mean diameters between 100 and 200?nm, have a positive surface charge, and could protect DNA against DNase I degradation. The CNPs prepared were successfully used to transfect the Df-1 cell line with almost no cytotoxicity. CNPs prepared at an amino group to phosphate group ratio (N/P ratio) of 16 provided the highest transfection efficiency (1.1%) in medium with a pH of 6.5. When pCAGG-ChIL2 CNPs were administered to chickens simultaneously with a DNA vaccine against Newcastle disease virus (NDV), haemagglutination inhibition antibody titers and serum interferon-γ (IFN-γ) levels were significantly higher than in chickens immunised with the NDV DNA vaccine alone (p?<?0.05). The results demonstrate that pCAGG-ChIL2 CNPs improve DNA vaccine-elicited immunity against NDV challenge.     

Induction of an in vitro reversible hypometabolism through chitosan-based nanoparticles

Objective: Chitosan-based nanoparticles (NPs) were prepared to promote intracellular sustained delivery of the synthetic delta opioid D-Ala(2)-D-Leu(5)-enkephalin (DADLE), prolonging peptide activity and inducing a safe and reversible hypometabolic state.

Materials and methods: NPs were prepared by combining ionotropic gelation and ultrasonication treatment. NP uptake studies and the effects of encapsulated DADLE on HeLa cells proliferation were tested by transmission electron microscopy (TEM) analysis, by immuno-fluorescence and immuno-cytochemistry.

Results: DADLE-loaded NPs are produced with suitable characteristics, a satisfactory process yield (55.4%?±?2.4%) and encapsulation efficiency (64.6%?±?2.1%). NPs are effective in inducing a hypometabolic stasis at a 10^?4?M DADLE concentration. Moreover, as seen from the immunofluorescence study, the effect persists through the recovery period (72?h). Indeed, NPs labelled by anti-enkephalin antibody inside cell nucleus reassert that the in vivo release of the peptide can be prolonged with respect to the case of free peptide supply.

Conclusion: The nanoparticulate drug delivery system described seems to be effective in inducing and prolonging a sort of hibernation-like state in the cells.