免疫磁性海藻酸钠载药纳米微球的制备与评价

靶向治疗系统是目前研究的热点,用微乳化-离子交联方法制备包覆阿霉素的碳包铁/海藻酸钠复合纳米微球,以水溶性碳二亚胺为交联剂,将载药微球与单抗Hab18连接,制备出了免疫磁性药物纳米微球.对该免疫磁性微球的理化性能进行了表征,同时检测了免疫磁性微球中抗体的活性和免疫磁性微球与靶细胞的体外结合情况,结果表明,免疫磁性药物纳米微球平均粒径约为171.2nm,外观为球型,铁含量为14.6%,载药量为10.8%,且具有强磁响应性和长时间药物缓释效果.同时在体外该微球能够与靶细胞特异性结合.这种免疫磁性药物纳米微球有望成为一种优良的靶向肿瘤药物载体.     

Haemorrhage-induced splenic vasodilation in the rat is mediated by sympathetic vasomotor nerves

A marked decrease in splenic vascular resistance, with an increase in blood flow to the spleen, occurs already 5 min after an acute and severe hypotensive bleeding in awake rats. This response is virtually abolished in rats pretreated with a β-adrenergic blocking agent. We have now studied the contribution of the sympathetic vasomotor innervation and of adrenal gland-derived catecholamines to the splenic vasodilation. Splenic blood flow was determined with the microsphere method in heavily bled (1.5% of body weight) awake rats. The sympathetic neurones in one group of rats had been chemically destroyed with 6-hydroxydopamine. In another group of rats we had removed the adrenal glands. In the control and in sympathectomized rats, splenic vascular resistance fell to 35 and 64%, respectively, of baseline 5 min after bleeding. Splenic blood flow about doubled during this period in the control rats, and then declined gradually to baseline over the next 24 h. In the sympathectomized rats, splenic blood flow decreased gradually over the first 12 h to reach 66% of baseline. The removal of the adrenal glands did not appreciably influence the splenic vascular response to bleeding. We conclude that an increased activity in the splenic sympathetic vasomotor neurones is a prerequisite for the observed vasodilation and concomitant large increase in splenic blood flow after haemorrhage in intact, awake rats. Catecholamines from the adrenal glands did not contribute detectably to the splenic vasodilation.     

生物降解性防术后粘连膜的实验研究

本文首次采用新型医用天然高分子材料壳聚糖作膜材料，制备了可降解吸收防术后粘连膜，并通过动物实验研究其生物降解性和生物相容性．初步研究结果表明，壳聚糖具有很好的成膜性。壳聚糖膜在小鼠体内可以缓慢降解，并具有较好的生物相容性，是一种很有发展前景的天然防术后粘连膜材料。     

微悬浮聚合法合成聚苯乙烯磁性微球

采用微悬浮聚合制备了聚苯乙烯磁性微球（简称磁球）。在苯乙烯磁流体中加入引发剂和交联剂,然后将此磁流体分散在水中,经过高速剪切乳化,形成较稳定的微悬浮液,然后进行聚合,可合成0.4μm-6μm,主要分布在0.7μm-2.0μm的磁性微球。利用激光粒度分布仪、透射电镜（TEM）以及热重仪（TG）研究了引发剂用量、初始单体用量、聚合温度、磁粉用量、二乙烯苯（DVB）用量等因素对磁球的粒径大小及其分布、凝结量以及磁含量的影响。     

5-氟尿嘧啶白及微球家兔肾动脉栓塞后体内药代动力学研究

以常规5-氟尿嘧啶(5-Fu)注射液为对照品,研究了5-Fu白及微球家兔肾动脉栓塞后体内药代动力学过程.血药5-Fu浓度采用反相高效液相色谱法,所得血药浓度数据用3P87药代动力学程序处理.实验结果5-Fu白及微球体内过程符合二室模型,t1/2a(6.27±6.10)min,t1/2β(203.6±97.5)min,Cmax(4.8±1.9)μg/ml.t1/2a,t1/2β均比注射剂明显延长(P<0.01).表明微球剂型具有靶向制剂长效、高效、低毒的特点.     

聚羟基丁酯酯缓释微球的制备及性能

用溶剂蒸发法制备了以新型生物可降解材料聚羟基丁酸酯为载体、以安定为模药的缓释微球,讨论了药物与载体之比对药物含量与包封率的影响,以及制备微球条件对药物释放性能的影响;微球平均粒径为３０～４０μｍ,粒径分布在１～１．５之间,最大载药量为１９．５１％;最高包封率为６７．１１％;体外累积释放曲线呈“两相”释放特征并拌随初始的“突释效应”。扫描电镜观察微球表面呈皱缩表观形态结构,微球内部横断面具有孔道与孔     

Toxicity of magnetic albumin microspheres bearing adriamycin

Magnetic albumin microspheres entrappingadriamycin ( ADM- MAM) is a novel chemothera-peutic compound with site- specific drug delivery,which was exploited and developed in 1 970 's[1] .However,there wasno detailinformation indexed onits toxicity[2 ] . In recentyears,we studied the toxici-ty of the compounds macroscopically and microscopi-cally and also gotits value of LD50 .1　METHODSAND RESULTSBased on the method previously reported[1] ,thecompound of ADM- MAM was synthesized[14 ]…     

Dose and Load Studies for Subcutaneous and Oral Delivery of Poly(lactide-co-glycolide) Microspheres Containing Ovalbumin

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 µm were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 µg of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fishers paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 µg OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freunds adjuvant.     

Polymeric Microspheres Prepared by Spraying into Compressed Carbon Dioxide

Purpose. The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO₂ (PCA-process) and to study the influence of various process parameters on their morphological characteristics. Methods. The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO₂ was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO₂ in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO₂ phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. Results. Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO₂. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. Conclusions. The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.     

5%声振人血白蛋白空气微球蛋白含量测定

采用高效液相凝胶色谱法（ＧＣ－ＨＰＬＣ）、醋酸纤维膜电泳和半微量定氮法测定５０％声振人血白蛋白空气微球制剂中球壁蛋白的含量。ＧＣ－ＨＰＬＣ确证了球壁蛋白主要成分为人血白蛋白;醋酸纤维膜电泳测定空气人血白蛋白微球制剂中人血白蛋白纯度＞９０％;半微量定氮法测出球壁蛋白含量平均值为３．５６％左右,９９％正常值范围为２．５２％－４．６０％。