SYNTHESIS OF MONODISPERSE HOLLOW POLYMER MICROSPHERES WITH FUNCTIONAL GROUPS BY DISTILLATION PRECIPITATION POLYMERIZATION

Monodisperse hollow polymer microspheres having various functional groups on the shell-layer, such as carboxylic acid, pyridyl and amide, were prepared by two-stage distillation precipitation polymerization in neat acetonitrile in the absence of any stabilizer or additive, during which monodisperse poly（methacrylic acid） （PMAA） afforded from the first-stage polymerization was utilized as the seeds for the second-stage polymerization. The shell layer with different functional groups was formed during the second-stage copolymerization of either divinylbenzene （DVB） or ethyleneglycol dimethacrylate （EGDMA） as crosslinker and the functional comonomers, in which the hydrogen-bonding interaction between the carboxylic acid group of PMAA core and the functional groups of the corresponding comonomers, including carboxylic acid, amide and pyridyl, played an essential role for the formation of monodisperse core-shell functional microspheres. The hollow polymer microspheres were then developed after the subsequent removal of PMAA cores by dissolution in ethanol under basic condition. Transmission electron microscopy （TEM） and scanning electron microscopy （SEM） were used to determine the morphology of the resultant PMAA core, functional core-shell microspheres and the corresponding hollow polymer microspheres with different functional groups. FT-IR spectra confirmed the successful incorporation of the various functional groups on the shell layer of the hollow polymer microspheres.

Elaboration of Materials with Functionality Gradients by Assembly of Chitosan-Collagen Microspheres Produced by Microfluidics

Biopolymers extracted from renewable resources like chitosan and collagen exhibit interesting properties for the elaboration of materials designed for tissue engineering applications,among which are their hydrophilicity,biocompatibility and biodegradability.In many cases,functional recovery of an injured tissue or organ requires oriented cell outgrowth,which is particularly critical for nerve regeneration.Therefore,there is a growing interest for the elaboration of materials exhibiting functionalization gradients able to guide cells.Here,we explore an original way of elaborating such gradients by assembling particles from a library of functionalized microspheres.We propose a simple process to prepare chitosan-collagen hybrid microspheres by micro-and milli-fluidics,with adaptable dimensions and narrow size distributions.The adhesion and survival rate of PC12 cells on hybrid microspheres were compared to those on pure chitosan ones.Finally,functionalized microspheres were assembled into membranes exhibiting a functionalization gradient.

Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

A method of elevated temperatures coupled with magnetic stirring to predict real time release from long acting progesterone PLGA microspheres

The object of the study was to develop a quick and reproducible accelerated in vitro release method to predict and deduce the function of the real time(37 °C) release for long acting PLGA microspheres. The method could be described in several steps. First, the release of the microspheres were studied using the sample and separate method at 37 °C with normal orbital shaking and elevated temperatures with magnetic stirring to further accelerate the release. Second, the most similar profile at elevated temperatures with the real time release was chosen with the help of the n value in the fitted Korsmeyer-Peppas Function. Third,the Weibull function and conversion ratio were used to deduce the function of real time release according to the chosen profile at elevated temperatures. The key point in this study was to provide a quick and precise method to predict the real time release for long acting progesterone PLGA microspheres. So the elevated temperatures coupled with magnetic stirring were used to accelerate the release further, and when there have many similar release profiles with the real time release at elevated temperatures, releasing time at elevated temperatures and the R2 of the final deduced function will be used to help choosing the most similar release profile with the real time release. Four different types of progesterone PLGA microspheres were used to verify the method, and all the deduced function correlated well with the real time releases, for R2 = 0.9912, 0.9781, 0.9918 and 0.9972, respectively.

Fabrication of Microporous Film and Microspheres Hybrids

Hybrids consisting of a microporous film and polymeric microspheres were fabricated via a simple method without a special apparatus. Highly ordered microporous polymer films with honeycomb structure were fabricated by a dissipative process utilizing amphiphilic poly(acrylic acid)- block-polystyrene, which was synthesized by atom transfer radical polymerization followed by an acid-catalyzed ester cleavage reaction. In order to embed the microsphere efficiently, the dried microporous films should be soaked in methanol to alter the surface functionality and to improve the wettability of the film surface. The introduction of amino functionality to polystyrene microspheres by seeded polymerization of N,N-dimethylaminoethyl methacrylate drastically improved the embedding efficiency. The effect of open pore size was also investigated.

Synthesis of Micron-size Functional Polystyrene Fluorescent Micro- spheres and their Adsorbability to Human Serum Albumin

Polystyrene microspheres with sulfo- or aldehyde- surface were synthesized through dispersion polymerization. Functional polystyrene fluorescent microspheres were prepared by the way of adding 2, 5-diphenyloxazole (PPO) into the reaction system directly and dying the blank microspheres in the ethanol solution of PPO. The influence of preparing matters on the encapsulating rate of PPO, and the influence of functional groups on the adsorbability to human serum albumin (HSA) were investigated.

基于纤维芯层流体力学方法制备聚合物功能微球研究进展

聚合物复合微球在医药、传感、光学、显示等领域,特别是在医药领域的临床诊断、病理成像和药物输送等方面具备重要应用价值。但是,聚合物复合微球的合成路线复杂、加工效率低下,常规工艺通常难以兼顾微球粒径单分散性、生产成本、产量等综合要求。近年来,纤维芯层流体力学方法依据纤维内发生的流体界面不稳定性(PRI)现象,可在微纳米尺度制备具有高度单分散性的聚合物微球,同时成本可控,适合批量生产。本文综述了流体界面不稳定性原理、纤维芯层PRI方法制备工艺、功能微球和结构微球的纤维芯层PRI方法制备等方面的最新进展,以及针对纤维芯层PRI方法的最新改进。

溶胶-凝胶法功能性有机硅微球研究进展

功能性有机硅微球既有无机骨架赋予的优异机械性能,也能通过有机基团实现功能化,在众多领域都很有应用前景。近年来,制备具有不同化学组成的功能性有机硅微球,调控微球的形貌结构并拓展其应用领域,已成为聚合物微球领域的研究热点之一。重点介绍了溶胶-凝胶法功能性有机硅微球的制备方法和特点,综述了其在色谱固定相、药物递送、光学材料、废水处理和改性剂等领域的应用研究进展,并展望了未来的发展方向。

流动聚焦型液滴微流控技术研究进展

功能性微球具有比表面积高、性能稳定、形貌多样等特点,广泛应用于药物控释、生物医学、污染物吸附和催化剂等领域。微球的制备方法有喷雾干燥法、悬浮聚合法、离子交联法、乳液蒸发法和液滴微流控法。液滴微流控技术试剂消耗量低,安全系数高,制备的微球单分散性高,其中利用流动聚焦型微流控技术制备液滴时可以有效防止液滴与壁面剪切,液滴尺寸更易调控。以流动聚焦型液滴微流控技术为立足点,综述了流动聚焦型的实验和数值模拟、功能性微球制备和集成放大的研究进展,为后续新型功能性微球的制备以及产业化大批量生产提供参考。

基于自转一阶非连续式微球双平盘研磨的运动学分析与实验研究

目的分析不同研磨压力、下研磨盘转速、保持架偏心距和固着磨料粒度对微球精度的影响,确定自转一阶非连续式双平面研磨方式在加工GCr15轴承钢球时的最优研磨参数,提高微球的形状精度和表面质量。方法首先对自转一阶非连续式双平盘研磨方式微球进行运动学分析,引入滑动比衡量微球在不同摩擦因数区域的运动状态,建立自转一阶非连续式双平盘研磨方式下的微球轨迹仿真模型,利用MATLAB对研磨轨迹进行仿真,分析滑动比对研磨轨迹包络情况的影响。搭建自转一阶非连续式微球双平面研磨方式的实验平台,采用单因素实验分析主要研磨参数对微球精度的影响,得到考虑圆度和表面粗糙度的最优参数组合。结果实验结果表明,在研磨压力为0.10 N、下研磨盘转速为20 r/min、保持架偏心距为90 mm、固着磨料粒度为3000目时,微球圆度由研磨前的1.14μm下降至0.25μm,表面粗糙度由0.1291μm下降至0.0290μm。结论在自转一阶非连续式微球双平盘研磨方式下,微球自转轴方位角发生突变,使研磨轨迹全覆盖在球坯表面。随着研磨压力、下研磨盘转速、保持架偏心距的增大,微球圆度和表面粗糙度呈现先降低后升高的趋势。随着研磨压力与下研磨盘转速的增大,材料去除速率不断增大,随着保持架偏心距的增大,材料去除速率降低。随着固着磨料粒度的减小,微球的圆度和表面粗糙度降低,材料去除速率降低。

Embosphere微球子宫动脉栓塞术与高强度聚焦超声对子宫腺肌病患者的影响

目的探讨Embosphere微球子宫动脉栓塞术(UAE)与高强度聚焦超声(HIFU)对子宫腺肌病(AM)患者的影响。方法回顾性分析2017年10月至2021年2月沧州市人民医院收治的120例AM患者的临床资料,根据不同治疗方法分为HIFU组和UAE组,每组60例。HIFU组采用HIFU治疗,UAE组采用Embosphere微球UAE治疗。比较两组治疗前后痛经情况、月经情况、子宫体积、病灶体积、临床疗效、卵巢功能、并发症发生率、1年内复发率及妊娠结局。结果治疗后6个月、1年,两组视觉模拟评分法(VAS)、月经失血图(PBAC)评分均低于治疗前(P<0.05)。治疗后6个月、1年,两组子宫体积、病灶体积均小于治疗前(P<0.05)。两组临床总有效率比较,差异无统计学意义(P>0.05)。治疗后6个月、1年,UAE组抗米勒管激素(AMH)、窦卵泡计数(AFC)均低于治疗前,且HIFU组AMH、AFC均高于UAE组(P<0.05)。两组并发症总发生率比较,差异无统计学意义(P>0.05)。HIFU组1年内复发率、妊娠率、活产率均高于UAE组(P<0.05)。结论Embosphere微球UAE与HIFU对AM的治疗效果相当,均可明显缩小病灶,有效改善痛经及月经量情况,Embosphere微球UAE远期复发率更低,HIFU对患者卵巢功能影响较小,有助于改善妊娠结局。因此,有生育意愿的患者首选HIFU治疗,无生育意愿的患者首选Embosphere微球UAE治疗。

Preparation of slightly crosslinked monodisperse poly(maleic anhydride-cyclohexyl vinyl ether-divinylbenzene)functional microspheres with anhydride groups via precipitation polymerization

Slightly crosslinked monodisperse poly（maleic anhydride-cyclohexyl vinyl ether-divinylbenzene） （MA-CHVE-DVB） microspheres were prepared via precipitation polymerization while using 2,2- azobisisobutyronitrile as an initiator in a mixture of methyl ethyl ketone and n-heptane without any stabilizer. The number-average diameter of the resultant poly（MA-CHVE-DVB） microspheres ranged from 0.478 to 1.386 μm with a polydispersity index of 1.00 to 1.02 that depended on the feed ratios of the MA/CHVE/DVB monomers. The introduction of one electron donor monomer cyclohexyl vinyl ether strongly affected the yield, size, and morphology of these slightly crosslinked microspheres. Quinoline- type chelating resins were obtained after combining the poly（MA-CHVE-DVB） with 8-hydroxyquinoline; the adsorption properties of these materials were measured through their ability to remove Cu^2＋ ions from water. The poly（MA-CHVE-DVB） microspheres with low degrees of crosslinking provided more effective functional groups and therefore better ion removal capabilities. These slightly crosslinked microspheres may have applications in water treatment as well as in sensing and drug delivery.

Amino-functionalized core-shell magnetic mesoporous composite microspheres for Pb(Ⅱ) and Cd(Ⅱ) removal

Amino-functionalized Fe3O4@mesoporous SiO/ core-shell composite microspheres NH2-MS in created in multiple synthesis steps have been investigated for Pb（Ⅱ） and Cd（Ⅱ） adsorption. The microspheres were characterized by transmission electron microscope （TEM）, scanning electron microscope （SEM）, N2 adsorption-desorption, zeta potential measurements and vibrating sample magnetometer. Batch adsorption tests indicated that NH2-MS exhibited higher adsorption affinity toward Pb（Ⅱ） and Cd（Ⅱ） than MS did. The Langmuir model could fit the adsorption isotherm very well with maximum adsorption capacity of 128.21 and 51.81 mg/g for Pb（Ⅱ） and Cd（Ⅱ）, respectively, implying that adsorption processes involved monolayer adsorption. Pb（Ⅱ） and Cd（Ⅱ） adsorption could be well described by the pseudo second-order kinetics model, and was found to be strongly dependent on pH and humic acid. The Pb（Ⅱ）- and Cd（Ⅱ）-loaded microspheres were effectively desorbed using 0.01 mol/L HC1 or EDTA solution. NH2-MS have promise for use as adsorbents in the removal of Pb（Ⅱ） and Cd（Ⅱ） in wastewater treatment processes.

Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels

We examined the effect of androgens on bladder blood flow （BBF）, bladder function and histological changes in castrated male rats. Male Wistar rats were classified into unoperated group （control group）, groups castrated at the age of 8weeks （group 8wPC） and groups castrated at the age of 4weeks （group 4wPC）. Each rat was used at the age of 20weeks. BBF was measured using fluorescent microspheres. Bladder cystometry was performed without anesthesia or restraint; the bladder was first irrigated with saline and then with 0.25% acetic acid （AA） solution. Maximum voiding pressure and voiding interval were measured. The bladder and lilac artery were histologically examined for differences in smooth muscle and quantity of collagen fiber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened （P 〈 0.001） following AA irrigation. No significant difference was noted in the maximum voiding pressure. Histological changes were observed in bladder and lilac artery. Smooth muscle/collagen ratio at the bladder was lower in groups 8wPC and 4wPC compared to the control group （P 〈 0.01）, while that at the lilac artery was decreased in group 4wPC compared to the control group （P〈 0.001）. In conclusion, our findings indicate that castration does not alter BBF, but leads to histological changes in the bladder as well as its associated blood vessels.

聚合物微球调驱剂研究进展

综述了聚合物微球调驱剂的聚合方法;根据聚合物微球的功能特点,重点介绍了荧光聚合物微球、磁性聚合物微球和智能聚合物微球的研究进展;论述了聚合物微球调驱性能和调驱机理主要的研究方法及研究现状;对聚合物微球调驱剂的未来发展趋势进行展望,提出多功能新型聚合物微球的设计合成及基于聚合物性质、流体性质等多种因素的调驱机理研究将成为未来的研究方向。

可吸收止血微球在前置胎盘剖宫产术中的应用效果

目的探究可吸收止血微球在前置胎盘剖宫产术中的应用效果。方法选取2018年1月至2021年3月海南省妇女儿童医学中心收治的80例行剖宫产术的前置胎盘孕妇,按照治疗方法不同分为观察组和对照组,每组40例。对照组采用常规预防性止血措施,观察组在对照组基础上加用可吸收止血微球治疗。比较2组患者术中和术后24 h出血量、出血时间、并发症发生率及子宫切除率,比较2组患者术前、术后24 h凝血功能[纤维蛋白原(FIB)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)]及应激指标[去甲肾上腺素(NE)、肾上腺素(E)、皮质醇(Cor)、血管紧张素Ⅱ(Ang-Ⅱ)]。结果观察组术中、术后24 h出血量均低于对照组(P<0.05),出血时间短于对照组(P<0.05)。术后24 h观察组APTT、PT、TT水平较对照组低(P<0.05),FIB水平较对照组高(P<0.05)。术后24 h观察组血清NE、E、Ang-Ⅱ、Cor水平较对照组低(P<0.05)。观察组并发症发生率较对照组低(P<0.05);2组患者子宫切除率比较差异无统计学意义(P>0.05)。结论可吸收止血微球应用于前置胎盘剖宫产术中效果显著,可有效减少术中及术后出血量,缩短出血时间,改善凝血功能,减轻术后应激,降低并发症发生率。

载药微球动脉灌注联合TACE治疗中晚期原发性肝癌的效果及对肝功能和生存率的影响

目的:观察载药微球动脉灌注联合肝动脉化疗栓塞术(TACE)治疗中晚期原发性肝癌的效果及对肝功能及生存率的影响。方法:选取2020年3月—2022年3月蚌埠医学院第二附属医院收治的70例中晚期原发性肝癌患者为研究对象,经随机数表法分为对照组与试验组,各35例。对照组应用TACE治疗,试验组应用载药微球动脉灌注联合TACE治疗。比较两组治疗效果、治疗前后肝功能[总胆红素(TBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(ALB)]指标、不良反应发生率及术后生存率。结果:试验组临床控制率、客观缓解率均高于对照组,差异有统计学意义(P<0.05)。治疗前、治疗1个月后,两组TBIL、ALT、AST及ALB水平比较,差异无统计学意义(P>0.05)。治疗1个月后,两组TBIL、ALT、AST及ALB水平均低于治疗前,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。术后3个月、6个月,两组生存率比较,差异无统计学意义(P>0.05),术后12个月,试验组生存率高于对照组,差异有统计学意义(P<0.05)。结论:中晚期原发性肝癌患者应用载药微球动脉灌注联合TACE治疗的效果确切,对肝功能影响较小,能够提升患者术后远期生存率。

基于聚偏氟乙烯复合结构色材料的制备与性能

以聚偏氟乙烯(PVDF)为黏结剂,将其填充于三维PS@SiO2光子晶体中,锁定PS@SiO2微球组装的有序阵列,成功构建了结构稳定且柔韧的新型PVDF/PS@SiO2结构色材料。使用纳米粒度与电位分析仪对PS@SiO2微球的多分散性指数以及Zeta电位进行了测试,采用SEM、TEM、固体紫外-可见光谱仪、预置式色牢度摩擦仪及拉伸测试仪对PVDF/PS@SiO2结构色材料的形貌、光学性质及稳定性进行了表征和测试。结果表明,该结构色材料在摩擦测试100次后,结构保持稳定,颜色稳定存在。同时材料易于图案化,具有优异的抗拉伸性能和柔性,材料的拉伸断裂应力达到22.28 MPa,断裂应变为28.49%,在卷曲100次后,依旧保持微观结构稳定。

聚乳酸-羟基乙酸共聚物微球在骨组织工程中的应用

背景:聚乳酸-羟基乙酸共聚物微球具有良好的生物相容性、生物安全性和生物降解性,作为载体已经被广泛应用于骨组织工程中,但其仍有缺乏亲水性、副产物酸性及缺乏功能化等缺点,因此需要进行不同的修饰改性方能更好地应用。目的:对聚乳酸-羟基乙酸共聚物微球在骨组织工程中的应用进行综述。方法:以“poly(lactic-co-glycolic acid)copolymer microsphere,PLGA microsphere,growth factor,drug deliver,modified,functional modification,composite scaffold,bone tissue engineering”为检索词在Web of Science和PubMed数据库检索自2000年1月至2022年6月收录的相关文献,并将其进行筛选和分析,最终选择83篇文献进行综述。结果与结论:①聚乳酸-羟基乙酸共聚物微球的理化性质与其乳酸和羟基乙酸比、分子质量和端基团等因素有关。目前,乳酸和羟基乙酸比例为75∶25、相对分子质量为75000-100000,端羧基的聚乳酸-羟基乙酸共聚物在制备微球时应用较多。②现在常用的制备方法主要包括乳化法、微流控技术、电喷雾、喷雾干燥和超临界流体法。具体的制备方法需结合微球的应用需求及生产条件来选择,随着技术的成熟与进步,未来会有更稳定、高效的生产方式。③聚乳酸-羟基乙酸共聚物微球的修饰改性包括负载生长因子和药物、功能化修饰以及以微球为基础构建复合支架。负载生长因子可促进细胞分化、血管生成,从而促进骨组织的修复与再生;负载药物可治疗多种骨骼类疾病;复合无机矿物可以提高聚乳酸-羟基乙酸共聚物的力学性能,而且提供骨组织生长所需的微量元素,更多的被用于骨缺损的治疗;通过增加微球调控细胞的分泌与活性的能力,参与疾病的免疫调控,为疾病治疗提供新思路;以聚乳酸-羟基乙酸共聚物微球为基础的复合支架,在支架原有的优点外,还能增加微创递送药物、缓释药物的能力,但是距离临床应用还需进一步研究证实。④聚乳酸-羟基乙酸共聚物微球在未来有望根据骨组织工程的不同需求,制定不同的修饰方法,从而生产出针对不同疾病具有特定功能的微球。