左旋多巴微囊胃内漂浮片犬体内药物动力学研究

目的建立左旋多巴微囊胃内漂浮片在比格犬体内的血药质量浓度的测定方法,并对其体内药动学行为进行研究。方法建立HPLC法测定血样中左旋多巴的质量浓度,流动相为水-甲醇(95∶5),其中水相含EDTA 0.08mmol·L-1、磷酸二氢钾70mmol·L-1、庚烷磺酸钠2.08mmol·L-1,流速为0.5mL·min-1,荧光检测,激发波长278nm,发射波长325nm。6只Beagle犬分别给予复方左旋多巴微囊胃内漂浮片,并在给药后多点前肢静脉采血。用该方法检测血浆中左旋多巴的质量浓度,用3P97计算药动学参数。结果该方法的线性范围为0.078²0μg·mL-1,最低定量限为0.078μg·mL-1,日内RSD<8.10%,日间RSD<13.52%,回收率为105.1%20μg·mL-1,最低定量限为0.078μg·mL-1,日内RSD<8.10%,日间RSD<13.52%,回收率为105.1%¹13.9%。左旋多巴微囊胃内漂浮片在犬体内的药时曲线符合单室模型,主要药物动力学参数分别为t1/2(1.09±0.46)h,tmax(1.32±0.54)h,Cmax(1.33±0.31)μg·mL-1;AUC为(3.31±1.26)μg·h·mL-1。结论该方法简单、快速,可用于比格犬的左旋多巴血药质量浓度的测定和药动学研究。     

乳化溶剂挥发法及在微囊化制剂中的应用

许多方法和技术被用来制备聚合物微粒。制备方法决定微粒的种类和粒径,影响微粒组成物之间的作用力。微囊化制剂不仅可以达到缓释及控释药物的作用,还可以掩盖药物的不良气味及口味,防止药物的降解,减少药物的毒副作用等。聚合物载体被广泛地应用于微粒的制备,可分为生物降解及非降解型。本文主要综述近几年乳化溶剂挥发法的作用特点及其制备的微粒制剂的研究进展。     

A New Approach in Gastroretentive Drug Delivery System Using Cholestyramine

We prepared cellulose acetate butyrate (CAB)-coated cholestyramine microcapsules as a intragastric floating drug delivery system endowed with floating ability due to the carbon dioxide generation when exposed to the gastric fluid. The microcapsules also have a mucoadhesive property. Ion-exchange resin particles can be loaded with bicarbonate followed by acetohydroxamic acid (AHA) and coated with CAB by emulsion solvent evaporation method. The drug concentration was monitored to maintain the floating property and minimum effective concentration. The effect of CAB: drug-resin ratio (2:1, 4:1, 6:1 w/w) on the particle size, floating time, and drug release was determined. Cholestyramine microcapsules were characterized for shape, surface characteristics, and size distribution; cholestyramine/acetohydroxamic acid interactions inside microcapsules were investigated by X-ray diffractometry. The buoyancy time of CAB-coated formulations was better than that of uncoated resin particles. Also, a longer floating time was observed with a higher polymer:drug resin complex ratio (6:1). With increasing coating thickness the particle size was increased but drug release rate was decreased. The drug release rate was higher in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). The in vivo mucoadhesion studies were performed with rhodamine-isothiocyanate (RITC) by fluorescent probe method. The amount of CAB-coated cholestyramine microcapsules that remained in the stomach was slightly lower than that of uncoated resin particles. Cholestyramine microcapsules were distributed throughout the stomach and exhibited prolonged gastric residence via mucoadhesion. These results suggest that CAB-coated microcapsules could be a floating as well as a mucoadhesive drug delivery system. Thus, it has promise in the treatment of Helicobacter pylori.     

微囊化异体坐骨神经组织细胞移植对大鼠脊髓损伤后c-fos表达的影响

目的探讨微囊化异体坐骨神经组织细胞移植对大鼠脊髓损伤后c-fos表达的影响。方法95只SD大鼠随机分为4组,A组为微囊化坐骨神经细胞移植组（30只）;B组为坐骨神经细胞移植组（30只）;C组为单纯损伤对照组（30只）,仅用明胶海绵填塞SCI腔隙;D组为正常对照组（5只）,仅打开椎管,暴露脊髓不作移植。用免疫组织化学的方法观察移植术后6h-14d脊髓中c-fos基因的表达情况。结果脊髓半横断损伤后对照组脊髓中6h、12h内表达c-fos阳性的神经元数增多,平均光密度值升高,至24h又明显增强。而A组脊髓后角内的c-fos表达明显低于同时间点的B组和C组（P〈0．05）。结论微囊化坐骨细胞移植可能降低c-fos的表达,并在一定程度上减轻脊髓的继发性损伤。     

壳聚糖相对分子质量对微囊及包裹肝细胞活性的影响

目的 观察壳聚糖相对分子质量对微囊机械强度和通透性及包裹肝细胞活性的影响.方法 通过微囊搅拌实验比较中、低分子量壳聚糖形成的微囊的机械强度,比较2种微囊对异硫氰酸荧光素标记的牛血清白蛋白(FITC-BSA)通透性,及细胞染色实验判断2种微囊包裹小鼠原代肝细胞活性的区别.结果 微囊搅拌100 min后中分子量壳聚糖微囊破损率100%,低分子量壳聚糖微囊破损率5%,两种微囊机械强度差异有统计学意义(P＜0.05),微囊溶液中加入HTC-BSA15 min后,低分子量壳聚糖微囊内荧光强度为4 AU,中分子量壳聚糖微囊内荧光强度为1.5 AU,两种微囊对FITC-BSA的通透性差异有统计学意义(P＜0.05),低分子量壳聚糖形成的微囊包裹肝细胞培养1周后细胞染色实验显示微囊中活肝细胞数为100%,中分子量壳聚糖形成的微囊包裹的活肝细胞数约为40%,两者差异有统计学意义(P＜0.05).结论 低分子量壳聚糖相对于中分子量壳聚糖更适合于作微囊的材料.

Abstract：

Objective To study the influence of molecular weight of chitosan on microcapsules and hepatocytes in microcapsules. Methods The mechanical strength, permeability to fluoresceine isothiocyanate-bovine serum albumin (FITC-BSA) and activity of hepatocytes in microcapsules were compared between two kinds of microcapsules made by low and middle molecular weight chitosan. Results After 100 min of stirring microcapsules, all middle molecular weight chitosan microcapsules were damaged, 5% low molecular weight chitosan microcapsules were damaged. There was significant difference in breakage rate of the mechanical strength between two microcapsules (P ＜ 0. 05). Fifteen min after addition of FITCBSA into microcapsule solution, fluorescence intensity in the low molecular weight chitosan microcapsules was 4 AU, and that in middle molecular weight of chitosan microcapsules was 1. 5 AU, suggesting there was significant difference in permeability to FITC-BSA between two kinds of microcapsules (P ＜ 0. 05).One week after culture of microencapsulated hepatocytes, staining test showed that 100% of liver cells in low molecular weight chitosan microcapsules were alive, while the number was about 40% in middle molecular weight chitosan microcapsules (P ＜ 0. 05). Conclusion Low molecular weight chitosan is more suitable as materials of microcapsules than molecular weight chitosan.     

APA微胶囊膜厚的理论计算与实验研究

以静电脉冲技术成功地制备了海藻酸-聚-L-赖氨酸-海藻酸（APA）生物微胶囊，结合元素分析方法，推导出膜厚的理论计算公式，通过扫描电子显微镜（SEM）和光学显微镜测定了囊膜厚度，实验结果表明膜厚的理论计算和实验测定值一致，APA微胶囊膜厚约为7-10μm。     

Complement Activation by Alginate–Polylysine Microcapsules Used for Islet Transplantation

Abstract: A foreign body reaction is frequently observed around implanted microcapsules of alginate–polylysine. Since complement activation can play a role in this reaction, we checked in vitro the ability of empty alginate–polylysine microcapsules to activate complement. Human serum was incubated with microcapsules, and complement activation was evaluated by two methods: the complement hemolytic activity (CH₅₀) and the assay of the C3adesArg fragment. The occurrence of complement activation in the presence of microcapsules was suggested both by a CH₅₀ decrease and by high C3adesArg levels despite C3adesArg adsorption to the capsule membrane. Capsule membrane protection against the cytotoxic effects of complement was also tested. No hemolysis occurred when microencapsulated sensitized sheep erythrocytes were incubated with activated complement. In conclusion, the microcapsule membrane can protect cells against activated complement fragments. Nevertheless, alginate–polylysine microcapsules do activate complement, and this effect must be considered for its use as an implant.     

马钱子碱微囊制备工艺的研究

目的制备马钱子碱微囊,考察其影响因素,找出最优方案。方法以壳聚糖和明胶为囊材,马钱子碱为囊心物,采用复凝聚法制备载药微囊。通过正交设计试验,以包封率、粒径为指标,确定最佳囊材比、囊心与囊材比及CaCl_2的浓度,确定最优配方。观察其形态,测定其包封率、粒径、载药量、Zeta电位等。结果通过正交实验,制备马钱子碱微囊的最优配方:壳聚糖浓度为5 mg/m L,明胶浓度为4 mg/m L,CaCl_2浓度为2%,囊心与囊材比为1∶3。3次平行制备所得的载药微囊的各参数的平均值:包封率为28.73%,粒径为2.15μm,载药量为10.6%,Zeta电位为12.61 mV。微囊分散性好,表面平滑完整,囊壁清晰,无粘连。结论以壳聚糖和明胶为原料的复凝聚法制备马钱子碱微囊具有较高的包封率,且稳定性好,制备工艺简单。     

应用人工神经网络研究制剂体内外相关性

以明胶为囊材制备了红霉素缓释微囊 ,并采用人工神经网络对微囊的体内外相关性进行研究 ,测定红霉素缓释微囊 12h的体外溶出数据 ,同时以家兔为实验动物 ,灌服微囊后测定血药浓度 ,所得数据训练神经网络系统 ,使之能够根据体外释放度的数据预测体内血药浓度。结果表明人工神经网络能够用于体内外相关性研究     

A review and current state of autonomic self-healing microcapsules-based dental resin composites

ObjectiveThis study systematically reviews the literature on self-healing microcapsule technology and evaluates the biocompatibility of self-healing microcapsules and the efficiency of crack repair within resin-based dental composites.MethodsAn electronic search was carried out using the following databases: MedLine (PubMed), Embase, the Cochrane Library and Google Scholar. All titles and abstracts of the articles and patents found were analysed and selected according to the eligibility criteria. Only studies published in English were included; the outcomes sought for this review were dental resin composites with self-healing potential. There were no restrictions on the type of self-healing system involved in dental resin composites.ResultsThe search yielded 10 studies and 2 patents involving self-healing approaches to dental resin composites. According to the current literature on self-healing dental resin composites, when a crack or damage occurs to the composite, microcapsules rupture, releasing the healing agent to repair the crack with a self-healing performance ranging from 25% to 80% of the virgin fracture toughness.SignificanceSelf-healing strategies used with resin composite materials have, to date, been bioinspired. So far, self-healing microcapsule systems within dental composites include poly urea-formaldehyde (PUF) or silica microcapsules. The main healing agents used in PUF microcapsules are DCPD monomer and TEGDMA-DHEPT, with other agents also explored. Silica microcapsules use water/polyacid as a healing agent. All self-healing systems have shown promising results for self-repair and crack inhibition, suggesting a prolonged life of dental composite restorations. More investigations and mechanical enhancements should be directed toward self-healing technologies in dental resin composites.