Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle

PurposeTo evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization.Materials and MethodsUnilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100–150 μm and 90–315 μm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization. Kidneys were harvested for macroscopic and histologic analysis of embolization success, biodegradability, and biocompatibility.ResultsEmbolization was technically successful in 15 of 16 animals. One animal died of anesthesia-related circulatory failure. The 100–150 μm MS were injected easily through 3-F catheters; the 90–315 μm MS tended to clog with intermittent catheter obstruction. DSA and MR imaging showed successful target embolization in 13 of 15 animals. In 2 animals, the entire kidney was affected owing to catheter clogging, including a reflux of MS while flushing. Control DSA and MR imaging showed increasing vascular reperfusion with time. Macroscopic and histologic analysis revealed necrosis/infarction in areas in which embolization was achieved. MS were extensively degraded after 16 weeks, and overall inflammatory reaction was mild.ConclusionsBiodegradable PDO-MS induced effective embolization of target vessels while demonstrating good biocompatibility. MS increasingly dissolved at 16 weeks, partial reperfusion started at week 1, and complete reperfusion started at week 8, thus offering possible advantages as a temporary embolic agent.     

顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究

对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50～200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。     

低分子量聚合物电解质的合成与性能

研究了低分子量梳状聚合物电解质的合成方法及结构，性能。首先合成了不同分子量的甲基丙烯酸聚乙二醇单甲醚酯，并进一步合成了分子量一万左右的梳状聚合物电解质，结果表明：反应严格按照反应方程进行，精制产物是非晶的梳状聚合物，本聚合物体系均存在两个玻璃化转变温度，一个在100℃左右，归属为梳状聚合物主链的玻璃化转变，另一个在－20摄氏度以下，归属于侧链玻璃化转变，在室温下侧链可以运动，有利于电活性物质的迁移和扩散，并用超微电极研究了该电解质的行为。     

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

用乳剂—溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球。微球中药物的释放速度随丙烯酸树脂ＥｕｄｒａｇｉｔＲＬ／ＲＳ比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减小，释药５０％所需时间与微球粒径呈良好线性。微球的释药速率也随药物含量的增加（从４．２％到１６．７％）而增大，并快于药物结晶的溶解速率，但药物含量达２６．６％时，微球释药速率明显下降并低于药物结晶的溶解速率。用差热分析和Ｘ射线衍射分析证明，药物含量为４．２，９．４和１６．７％的微球中药物完全是以非晶态分散的，而含药２６．６％的微球中有药物结晶存在。不同微球释药低于７０％时，释放方式均符合Ｈｉｇｕｃｈｉ时间平方根方程。     

Effect of Glass Transition Temperature on the Stability of Lyophilized Formulations Containing a Chimeric Therapeutic Monoclonal Antibody

Purpose. The purpose of this study is to highlight the importance of knowing the glass transition temperature, T_g, of a lyophilized amorphous solid composed primarily of a sugar and a protein in the interpretation of accelerated stability data. Methods. Glass transition temperatures were measured using DSC and dielectric relaxation spectroscopy. Aggregation of protein in the solid state was monitored using size-exclusion chromatography. Results. Sucrose formulation (T_g ~ 59°C) when stored at 60°C was found to undergo significant aggregation, while the trehalose formulation (T_g ~ 80°C) was stable at 60°C. The instability observed with sucrose formulation at 60°C can be attributed to its T_g (~59°C) being close to the testing temperature. Increase in the protein/sugar ratio was found to increase the T_gs of the formulations containing sucrose or trehalose, but to different degrees. Conclusions. Since the formulations exist in glassy state during their shelf-life, accelerated stability data generated in the glassy state (40°C) is perhaps a better predictor of the relative stability of formulations than the data generated at a higher temperature (60°C) where one formulation is in the glassy state while the other is near or above its T_g.     

生物活性材料义眼台

由于病变和外伤等原因，使一些人眼球摘除，留下外现缺陷。医学上使用义眼台植入眼眶，在上面按装义眼以矫治外形。从前使用的义眼台用玻璃球或硅橡胶制作，使用中均有种类不同的缺点，即无生物活性、密度大等。医学界希望有新型医用材料临床应用。采用液态化学方法合成羟基磷灰石，使羟基磷灰石和微晶玻璃混匀，制成生物活性材料。生物材料和粘结剂、造孔剂，辅助剂一同制成生坯，以适当的温度焙烧成多孔结构义眼台。对材料进行了动物实验与临床应用。动物实验表明，材料具有优异的生物相容性和一定的生物活性。临床应用效果良好。本材料是制备义眼台的新材料。本文就材料研究、动物实验、义眼台的生产工艺进行了探讨。     

In vivo induction of CD4+ T cell responses by antigens covalently linked to synthetic microspheres does not require adjuvant

Macrophages, dendritic cells or B lymphocytes have been shownto play a major role in the presentation of soluble antigensto CD4⁺ T cells. In contrast, the capacity of these cells topresent particulate antigens such as bacterial or parasiticantigens to T cells remains controversial. To investigate thisquestion, well defined particulate antigens were prepared bycovalent linkage of proteins or peptides to 1 µm in diametersynthetic microspheres. The T cell immunogenicity of such particulateantigens was analyzed in vitro and in vivo. In vitro, a solubleprotein such as hen egg lysozyme (HEL) coupled to beads stimulateda strong proliferative T cell response of lymph node cells fromHEL-primed mice or of specific T cell hybridomas. HEL coupledto beads was presented to the specific T cell hybridomas bysplenocytes or by peritoneal macrophages, but not by lymphomaB cells. Immunization of mice with several different proteinantigens or with a synthetic peptide covalently linked to beadsinduced strong CD4⁺ T cell responses in the absence of adjuvant.The strong in vivo immunogenicity of proteins coupled to beadsdid not result from a non-specific adjuvant effect of beadssince covalent linkage of the antigen to beads was strictlyrequired to induce T cell responses in the absence of adjuvant.In vivo treatment by carrageenan showed that macrophages arerequired for the in vivo stimulation of T cell responses bythese particulate antigens. Thus, these results demonstratedthe role of phagocytic cells, especially macrophages, for invivo presentation of particulate antigens. These particulateantigens represent an interesting approach for the developmentof new vaccines, and for the in vivo analysis of the role ofvarious antigen presenting cells in T cell activation and differentiation.     

白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。