Preparation and evaluation of 188Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy

Radioembolization with radioactive microspheres has been an effective method for the treatment of liver lesions. The aim of this study was to prepare carrier‐free ¹⁸⁸Re loaded poly (L‐lactic acid) (PLLA) microspheres through ¹⁸⁸Re sulfide colloidal nanoparticles (¹⁸⁸Re‐SC nanoparticles). The formation of ¹⁸⁸Re‐SC nanoparticles was confirmed by ultraviolet‐visible spectrophotometry. The labeling yield of ¹⁸⁸Re‐SC nanoparticles was verified using the RTLC method. Effects of synthesis parameters on morphology and size of prepared ¹⁸⁸Re‐sulfide colloidal‐PLLA microspheres (¹⁸⁸Re‐SC‐PLLA microspheres) were studied by scanning electron microscopy. In vitro stability of ¹⁸⁸Re‐SC‐PLLA microspheres was investigated in normal saline at room temperature and in human serum at 37°C. In vivo distribution studies and gamma camera imaging were performed in healthy BALB / c mice. The microspheres could be prepared with sizes between 13 and 48 μm (modal value 29 μm) and radiolabeling efficiency >99%. After incubation, the microspheres were found stable in vitro up to 72 hours. The biodistribution after intravenous injection in healthy BALB / c mice showed high accumulation in lung as a first capture pathway organ for microsphere followed by great retention over 48 hours for these microspheres. These data show that ¹⁸⁸Re‐SC‐PLLA microspheres are suitable candidate for clinical studies.     

Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release

Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system.     

平阳霉素磁性微球靶向治疗的实验研究

本研究用自制的一种新型平阳霉素磁性微球对人粘液表皮样癌裸鼠模型进行了治疗实验。实验结果表明，在外磁场作用下治疗效果明显好于游离平阳霉素。平阳霉素磁性微球提高了药物在局部的浓度，减轻了平阳霉素的毒副作用，延长了裸鼠的存活期     

顺铂—白蛋白微球舌动脉导向治疗舌鳞癌的药物释放研究

目的　研究顺铂—白蛋白微球 (CDDP_AMS)舌动脉导向治疗舌癌时 ,顺铂 (DDP)在体内和肿瘤局部的释放情况。方法　采用自行研制的平均粒径为 5 6 3μm的CDDP_AMS 10 0mg(含CDDP 13 6mg) ,经舌动脉推注治疗舌部鳞癌患者 7例 ,分别测定患者外周静脉血和肿瘤切除标本组织匀浆中的铂含量 ,并与单纯CDDP给药组患者相比较 ,分析CDDP_AMS药物释放的特点。结果　CDDP_AMS舌动脉推注治疗舌部鳞癌组 ,患者外周静脉血平均血药浓度在 90min时达峰值 ,10d时血药浓度尚可测到 ;肿瘤局部药物浓度可较长时间维持恒定 ,到第 17天时尚可测到。结论　CDDP_AMS具有很强的缓释作用 ,起到了药物“贮存站”作用 ,达到肿瘤局部长时间高浓度、全身外周血低浓度的效果 ,消除了CDDP全身大剂量用药时的毒副作用 ,值得推广应用     

磁控血管内磁性微球栓塞实验研究

将三种不同粒径聚甲基丙烯酸甲酯磁性微球分别注入磁场控制的股动脉、进行血管内磁性微球栓塞研究，术后Ｘ片、股动脉造影及病理检查显示，磁控时间５ｍｉｎ，不能形成稳固磁栓，磁控时间１５ｍｉｎ，３０－５０μｍ磁性微球组有稳固磁栓形成；磁控时间３０ｍｉｎ，则均能形成稳固磁栓。     

Functionalized Polycaprolactone/Hydroxyapatite Composite Microspheres for Promoting Bone Consolidation in a Rat Distraction Osteogenesis Model

Distraction osteogenesis (DO) is an ideal model to study bone regeneration. The major limitation is the relatively long period required for new bone consolidation. Here, we investigated whether the application of polycaprolactone (PCL) and hydroxyapatite (HA) composite microspheres could enhance bone formation in DO. Pure PCL microspheres and composite PCL and 10% HA microspheres were synthesized. Bone mesenchymal stem cells isolated from green fluorescent protein rats (GFP-rBMSCs) were cultured with microspheres in a rotary bioreactor system. Scanning electron microscopy was used to examine the microstructures. Osteogenic differentiation of rBMSCs was confirmed. Moreover, PCL/HA (20 mg) and PCL (20 mg) were locally administered into the distraction gap in the rat DO model toward the end of the distraction period. Imaging detection, mechanical and histological examinations were performed to assess the quality of the 4-week regenerates. Results showed that the microspheres were of uniform size and monodisperse. After incubation with rBMSCs in culture, PCL/HA microspheres showed a better ability for cell adhesion and osteogenic differentiation compared with PCL microspheres. In vivo, bone volume/total tissue volume, bone mineral density, and mechanical properties of the new callus were significantly higher in the PCL/HA group compared with the PCL group. Histological analyses confirmed improved bone formation and vascularization in PCL/HA group. We presented an effective protocol for the generation of functionalized microspheres and demonstrated implantation of PCL/HA microspheres into the distraction regenerate could significantly enhance bone consolidation. Thus, the application of PCL/HA composite microspheres may be a novel approach for promoting bone regeneration. This article is protected by copyright. All rights reserved © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:961-971, 2020     

预防用药对激素性股骨头血流量和血液流变学的影响

目的探讨应用药物预防激素性股骨头坏死。方法给予类固醇激素,诱导出兔股骨头坏死动物模型,同时使用血塞通、脂必妥和阿仑膦酸钠治疗,观察血液流变学指标和股骨头血流量。结果该方法可增加模型动物股骨头血流量,改善血液流变学指标,其增加或改善幅度与激素组相比有显著差异(P<0．05)。结论在长程使用类固醇激素同时应用血塞通、脂必妥和阿仑膦酸钠可提高股骨头血流量,改善血液流变学指标预防或减缓激素性股骨头坏死。     

羟基磷灰石／壳聚糖复合微球的制备及其生物学作用的体外研究

目的：通过探究羟基磷灰石（HAp）壳聚糖（CS）复合微球支架对骨髓间充质干细胞体外生物学行为的影响,评估其作为骨组织工程支架的可行性。方法纳米 HAp 和CS 复合物通过微流体技术自组装成微球支架,显微镜下形态学观察。将 P2代骨髓间充质干细胞（BMSCs）与微球行体外共培养,计算前6 h 黏附率。培养1、3、6、9 d,计算增殖率并用 GraphPad Prism 6软件对数据进行处理;行扫描电镜及共聚焦扫描式显微镜检测,观察细胞黏附及分布。将细胞微球复合物填入自制模具中培养14～21 d,进行形态观察。结果显微镜镜下微球为完整的圆形,大小一致。BMSCs 与微球体外培养6 h,黏附率达90％以上。6 d 时,BMSCs 的增殖率达到最高。扫描电镜结果显示微球上有大量 BMSCs 黏附定植并分泌大量胞外基质将微球连接成整体;共聚焦扫描式显微镜结果可见明显的细胞骨架微丝蛋白。细胞微球体外模具培养18 d 后,形成了结构完整的组织块。结论HAp-CS 微球是一种良好的促BMSCs 种子细胞黏附定植的支架材料,是促进细胞生长的有效支撑载体,与共培养细胞形成的复合组织块有望应用于体内动物实验修复标准缺损。