载体材料与载药微粒的释放性能：介观模拟和实验分析

选用可降解聚合物PLA,PLGA和固体脂三硬脂酸甘油酯、三嵛酸甘油酯为载体,制备包载布洛芬药物的载药微粒.通过DSC、XRD等测试分析和计算机介观模拟,从载体与药物的相容性、药物在载体中的分布状态等,探讨了载体材料对药物包封率和释放性能的影响.药物与载体的相容性好有利于药物的包封;药物均匀分布在载体中,将减缓药物的释放速率.以三硬脂酸甘油酯、三嵛酸甘油酯为载体时,药物分布在载体的外层空间,以PLA,PLGA为载体时,药物分布在载体内部,结果显示,聚合物载药微粒体外释放速率小于固体脂载药微粒.因而聚合物载药微粒更适合需要长时间缓慢释放的情况.     

不同溶剂条件下利用SEDS法制备乙基纤维素微粒的实验研究

分别利用二氯甲烷、丙酮和乙醇作为溶剂采用超临界流体增强溶液分散法(SEDS)制备了乙基纤维素微粒,考察了不同压力、温度和溶剂条件下所制备微粒的粒径大小及形态。实验表明:在体系亚临界和超临界状态下制备的微粒粒径及形态完全不同;聚合物的玻璃化温度的降低对微粒的形态影响比较大;溶剂对微粒粒径及形态也有较大影响,特别是对可制备微粒的压力及温度的范围的影响。     

超临界流体技术制备生物可降解聚合物/药物纳米微粒研究进展

生物可降解聚合物/药物纳米微粒在药物靶向递送、有效成分封装和医疗诊断等领域具有突出的优势。超临界流体超细微粒制备技术具有绿色环保、制备方法种类多、粒径易调节和后续分离纯化容易等特点,得到了广泛的研究。为了得到满足使用要求的聚合物/药物纳米微粒,超临界流体制粒技术是有效的手段之一。论述了生物可降解聚合物纳米材料的特点和应用情况,简要介绍了超临界流体及特性,重点介绍了超临界溶液快速膨胀(RESS)、超临界抗溶剂沉淀(SAS)、超临界CO₂辅助雾化(SAA)和超临界流体乳液萃取(SFEE)的工艺特点、制备方法、基本原理和研究进展,并对超临界流体技术制备聚合物/药物纳米微粒的发展方向进行了展望。     

氮气增强溶液雾化技术制备聚乙二醇微粒

以超临界流体增强溶液分散技术为基础,用N2取代C02以实现该过程更好的雾化效果.实验研究以聚乙二醇(PEG6000)/丙酮溶液制备PEG微颗粒,探讨预膨胀压力和溶液流量对粒径及粒径分布的影响.结果表明,超临界N2增强的溶液雾化技术可以制得形态基本上为球形的PEG微粒,并且粒径分布可以方便地控制在1～5μm.PEG微粒随预膨胀压力增大而减少,粒径分布变窄;低PEG/丙酮溶液流量下制备的微粒粒径分布较窄.     

超临界流体技术在制备复合载药微粒领域中的应用

介绍了超临界流体(SCF)技术制备复合载药微粒的原理、特点,总结了近几年SCF技术在制备药物复合微粒方面的研究情况,并就超临界流体技术应用于药物制剂方面的前景进行了探讨。     

星形共聚物聚己内酯-聚丙烯酸羟基乙酯的合成与载药性能

通过原子转移自由基聚合(ATRP)制备了两亲性线形共聚物聚己内酯-聚丙烯酸羟基乙酯(LPCLPHEA)及四臂星形共聚物聚己内酯-聚丙烯酸羟基乙酯(4s PCL-PHEA),以芘为荧光探针,测定两种聚合物的临界胶束浓度(CMC),并以阿霉素(DOX)为模型药物,分析探讨聚合物的载药能力。实验通过红外光谱(FT-IR)、荧光分光光度计、马尔文激光粒度仪等对聚合物的结构、粒径、Zeta电位、载药等性能进行表征。结果表明,两种聚合物都能形成稳定的载药胶束,其中四臂星形结构聚合物比线形聚合物具有较低的粒径和临界胶束浓度、较高的载药量和包封率,可作为药物载药材料进行进一步研究。     

交联聚合物微粒改性乳液聚合物工艺研究

采用乳液聚合法合成了成膜性很好的聚合物乳液和交联聚合物微粒 (CMP)乳液 ,并将二者共混 ,研究了CMP对聚合物乳液的成膜性及膜性能的影响 ,试验表明CMP对合成的乳液聚合物涂膜有增强作用 ,但其改性工艺仍需改进。对CMP的合成稳定性、成膜性和膜强度以及功能单体对CMP的改性性能也进行了讨论     

两步反相微乳液法原位制备纳米SiO2/聚甲基丙烯酸甲酯复合微粒

采用两步反相微乳液法原位聚合制备纳米SiO2／聚甲基丙烯酸甲酯(polymethylmethacrylate,PMMA)复合微粒。首先,通过混合2个分别增溶有2种反应物的微乳液,制备纳米SiO2粒子;然后,向混合后的微乳液中滴加单体及引发剂,通过单体的原位聚合反应得到SiO2,PMMA复合微粒。通过相图研究：确定了微乳液法制备复合微粒时初始组分的用量。通过透射电子显微镜、红外光谱、热重分析、X射线光电子能谱等手段对复合微粒进行了表征。结果表明：聚合后的PMMA包覆在SiO2表面．复合微粒的平均粒径为30nm．分散性良好。复合微粒中不能被抽提出来的聚合物占10．08％,这部分聚合物以Si-O-C键形式接枝在SiO2表面。     

长效载药微粒研究进展

长效载药微粒可使药物在几周或几个月内以一定速率释放,以维持有效血药浓度,减少给药次数,提高疗效。延长药物在体内的时间和有效控制药物的释放速率是长效载药微粒需要解决的两个基本问题。该文就延长载药微粒在体内的循环时间、延长载药微粒在吸收部位的停留时间、控制药物在释放初期的“突释”3个方面的研究进展进行了综述,并对长效微粒释药系统研究中的相关问题进行了讨论。引用文献42篇。     

新型非浸润模板法制备抗癌载药微粒的研究进展

近年来,能够精确控制尺寸、形态、组成的纳米微粒制备方法的研究成为科学研究的难点与热点。本文简述了一项新型的纳米微粒制备技术：非浸润模板微印制技术（PRINT,particle replication in non-wetting templates）,该技术是将微细加工技术应用到材料合成领域,以不亲水不亲油的含氟材料为模板,预先根据所需微结构的尺寸、形态设计制作模板,利用模板的空间局限作用,压印制备特定尺寸、形态、取向、排布的单分散载药微粒。重点阐述了PRINT技术微粒制备的方法以及在抗癌载药微粒的制备与应用,最后总结指出由PRINT技术制备的多种不同高宽比的形态抗癌载药微粒在病体细胞中具有不同的释药效果,该项技术在纳米微粒制备领域的突破有望推动纳米医药与生物诊断研究领域的巨大发展。     

Characterization of molecular interaionic and intraionic crosslinkable sulfonated poly(ether ether ketone‐alt‐benzimidazole) membrane

Lysozyme-loaded polymeric composite microparticles were successfully coprecipitated by solution-enhanced dispersion by supercritical CO₂ (SEDS), starting with a homogeneous organic solvent solution of lysozyme/poly(L -lactide)/poly(ethylene glycol) (lysozyme/PLLA/PEG). The effects of different drug loads (5, 8, and 12% w/w), PLLA Mw (10, 50, 100, and 200 kDa), PEG contents (0, 10, 30, and 50% PEG/(PLLA+PEG) w/w), and PEG Mw (400, 1000, and 4000 kDa) on the surface morphology, particle size, and drug release profile of the resulting composite microparticles were investigated. The results indicate that the size of the microparticles decreased and the rate of drug release increased with an increase in drug load, PEG content, or PEG Mw; the particle size first increased and then decreased with an increase in PLLA Mw, and the drug release was controlled by both particle size and PLLA Mw. The Fourier transform infrared spectrometer analysis and circular dichroism spectra measurement reveal that no significant changes occurred in the molecular structures during the SEDS processing, which is favorable to the production of protein–polymer composite microparticles for a protein drug delivery system. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Study on Precipitation of Astaxanthin in Supercritical Fluid

As health hazards of synthetic pigments are continuously found, more and more natural food pigments have been applied to the food industry. Astaxanthin is one of carotenoids that have been widely used in the food, cosmetic and pharmaceutical industries as natural colorants. In this paper, the micronization of astaxanthin in dichloromethane via the solution enhanced dispersion by supercritical fluids through prefilming atomization (SEDS-PA) process has been successfully performed. Morphologies and particle sizes (PSs) of the astaxanthin microparticles were analyzed by scanning electron microscopy (SEM). The results of micronization show that astaxanthin crystals with PSs about 20-30 µm have successfully been micronized to the microparticles with PSs about 0.5-6.0 µm by the SEDS-PA process. The effect of experimental variables on micronization of the astaxanthin has been studied. With the increase of initial solution concentration, the PSs of astaxanthin microparticles decrease initially, then increase. With the increase of solution flow rate and temperature, the PSs of astaxanthin microparticles increase. With the increase of pressure, the PSs of astaxanthin microparticles decrease. The nubbly particles were obtained in SEDS-PA process, and the crystallinity change of astaxanthin was showed by X-ray powder diffraction patterns (XRD).     

Preparation of Emodin‐Polyethylene Glycol Composite Microparticles Using a Supercritical Antisolvent Process

Emodin‐polyethylene glycol (PEG) composite microparticles were obtained from a dichloromethane‐methanol mixture via the solution‐enhanced dispersion by supercritical fluids through prefilming atomization (SEDS‐PA) process. Morphologies, particle sizes (PSs), and emodin contents of the composite microparticles were analyzed by scanning electron microscopy and UV‐visible spectrophotometry. The crystallinity change of emodin before and after the SEDS‐PA process was demonstrated by X‐ray powder diffraction (XRD). The composite microparticles present nubbly, rod‐like emodin dispersed in PEG or a nubbly, sheet emodin inlay on PEG, with PSs ranging between 3 and 12 μm. The PSs of the composite microparticles increase with the increase of temperature, decrease with the increase of pressure, and do not seem to depend on the emodin content of the initial solute and on the solution flow rate. The emodin contents of the composite microparticles increase with the increasing emodin content in the initial solute and temperature and decrease with increasing solution flow rate.     

稠密气体抗溶剂沉淀的过程特征及其放大中的若干思考

稠密气体抗溶剂沉淀在微粒制备中得到广泛应用,主要用于药物、食品、化妆品和一系列精细化学品中.介绍了GAS(SAS),ASES,SEDS和PGSS等过程的流程和特征.上述工艺不仅可以制备单组分微粒,还可以制备复合微粒,为活性物质的成功缓慢释放创造了条件.相对而言,稠密气体抗溶剂沉淀的实验室规模制备微粒已较成熟,但对有些实验现象尚难给出满意的解释,操作条件与产物粒径和形态间的比较准确的关系也尚未建立,距放大到工业规模形成生产力尚有相当大的差距,主要表现在缺乏定量描述过程的模型,即使是关联模型也鲜见报道,更不要说预测模型.因此难以建立在装置尺寸和结构与过程参数以及产品尺寸和形态间的有效联系.究其原因还是应用基础研究不足,对过程实质理解不深之故.在分析过程特征的基础上,讨论了过程放大的途径以及目前存在的问题和今后开发研究中应着重关注的各个层面.     

One-pot synthesis of gelatin-based,slow-release polymer microparticles containing silver nanoparticles and their application in anti-fouling paint

Gelatinous polymer matrix microparticles containing silver nanoparticles (AgNPs) were prepared by a novel method to obtain quasi non-swelling anti-fouling paint additives with slow-release characteristics. A w/o type dispersion were elaborated with the aqueous phase of gelatin, urea, silver-nitrate and formaldehyde dispersed in linseed oil. Gelatin was cross-linked by formaldehyde, together with urea for limiting the swelling of the product. Silver-nitrate was reduced with the assistance of gelatin and formaldehyde into homogenously dispersed AgNPs. The microparticles and embedded AgNPs were visualized by scanning and transmission electronmicroscopy. Encapsulated AgNPs with ∼18 nm crystallite size were identified by X-ray powder diffraction. Characterization of gelatin–urea–formaldehyde polymer matrices was carried out by attenuated total reflectance FTIR spectroscopy. Silver dissolution from microparticles and paints with AgNP-containing microparticles was measured by inductively coupled plasma spectrometer and resulted in highly sustained release, compared to unmodified gelatin microparticles and paints containing uncapsulated silver salts. A 7-month-long fouling experiment run in natural sweetwater media showed that solvent-based acrylic paint with AgNPs-containing gelatinous microparticles as additives offered resistance against biofouling at low Ag-release ratio.     

Sound absorption characteristics of polymer microparticles

A sound absorption material composed of polymer microparticles and polyurethane (PU) foam with certain geometry cavum has been developed. Its sound‐absorbing characteristic was investigated in the impedance tube, according to transfer function method. Measurements show that polymer microparticles have remarkable effect on the absorption performance of the composite material because of their microstructures and features. Several models established for acoustic properties have been adopted to fit the experimental data. The results show that these models fail to predict accurately the acoustic properties of the materials. The sound energy attenuation in polymer microparticles material may most likely consist of two parts, viscous attenuation of air inside the pores and the friction energy caused by the oscillation of polymer particles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2673–2679, 2006     

Micronization of Gefitinib Using Solution‐Enhanced Dispersion by Supercritical CO2

The antineoplastic gefitinib has a low aqueous solubility, leading to poor absorption rates. To overcome this problem, microparticles (MP) were prepared using solution‐enhanced dispersion by supercritical fluids (SEDS) with supercritical CO₂ and the cosolvents dichloromethane and ethanol. The results showed that the use of SEDS resulted in the formation of smaller particles and rendered the usually heterogeneous crystals of the crude drug pure and uniform. Furthermore, the reduction in the MP size increased the dissolution rate of gefitinib, and in vitro cytotoxicity assays indicated that the MP inhibited the proliferation of A549 cells to a larger extent than did the crude drug. Given the beneficial properties of the MP, SEDS could potentially be used to micronize drugs for therapeutic applications.     

基于超临界流体抗溶剂原理的造粒技术及其装置研究进展

超临界抗溶剂造粒技术由于具有操作条件温和、制得的微粒有机溶剂残留少、微粒粒径和形态可控等优点,已广泛地应用于药物运输体系的研究当中。本文简要介绍了超临界抗溶剂造粒技术的基本原理、装置组成和基本分类;从技术发展、喷嘴改进、技术结合、产品收集等方面,详细阐述了GAS、ASES、SEDS、SEDS-PA、SpEDS、SAS-EM、SAS-IJ、连续式RESS以及RESAS等基于超临界流体抗溶剂原理的造粒技术及其装置的改进过程;然后对目前其中存在的颗粒团聚、产品收集难和装置资源没有充分利用等问题提出了可能的解决方案;最后从数学模型的建立和规模化两方面,对超临界抗溶剂造粒技术基础理论的完善及其装置的改进进行了展望。     

Fabrication of composite microparticles of artemisinin for dissolution enhancement

The main aim of this study is to enhance the dissolution of a poorly water soluble antimalarial drug, artemisinin (ART) by fabricating its microparticles and composites with selected hydrophilic polymers using a spray drier with a modified multi-fluid nozzle. We investigated the spray drying of ART with polyvinylpyrrolidone (PVP) considering the effect of feed ratio (ART:PVP) on the physical properties and dissolution of spray dried ART. Other hydrophilic carriers such as polyethylene glycol (PEG) were selected for comparing the dissolution with that of spray dried ART with PVP. The drug and polymer solutions were supplied through different liquid passages of the modified four-fluid nozzle to fabricate ART and composite microparticles. Characterization of the original ART powder, spray dried ART microparticles and ART-polymer composite microparticles was carried out by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The DSC and XRD studies suggested that the crystallinity of ART decreased after spray drying and depended on the weight ratio of drug to polymer. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor (f₁) and similarity factor (f₂) were calculated for the statistical analysis. The dissolution of ART from the spray dried ART-PVP composite microparticles was more rapid than that from their respective physical mixture, spray dried ART-PEG composite microparticles and original ART powder. In the mathematical modeling, the Weibull and Korsmeyer-Peppas model were found to best fit to the in vitro dissolution data and the drug release kinetics could be recognized as Fickian diffusion. This study demonstrated that the modified multi-fluid spray drier can be used for the preparation of drug microparticles to improve the dissolution ability of poorly water soluble drugs and overcome the problem of finding a common solvent for drugs and carriers.