载阿霉素聚乳酸多孔微球的表征及释药性能

以阿霉素（DOX）为小分子化学药物模型,采用吸附法对聚乳酸（poly-L-lactide,PLLA）多孔微球进行载药,采用场发射扫描电子显微镜（FE-SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRPD）及差示扫描量热（DSC）对DOX-PLLA复合微球的形貌粒径及空气动力学性能、药物及材料的理化性能、载药性能进行表征,并且研究了其载药量、包封率和体外释放性能。结果表明,不同载药量之间的PLLA多孔微球粒径并无显著差异,均具有良好的空气动力学性能,适合肺部可吸入给药的条件;化学组成未见明显改变,物理结构由结晶态变为无定形态;随载药量的增加（2.9%,4.0%,4.6%）,包封率逐渐降低（56%,51%,44%）;药物的体外释放与原料药相比具有一定的缓释效果,最长释放时间可达5天,表明DOX-PLLA复合微球有望作为缓释制剂用于肺部给药。     

新型悬浮聚合法制备多孔磁性高分子微球的研究

采用新型悬浮聚合法制备了平均粒径为4.06 μm的多孔磁性高分子微球.以硅烷偶联剂KH-570对羰基铁粉颗粒进行表面修饰,并经一步聚合得到多孔磁性高分子微球.SEM结果表明该微球表面由纳米级聚合物粒子层层粘合而成,粒子间孔径在几十到几百纳米之间不等.采用红外光谱及X射线衍射表征了多孔磁性高分子微球的化学成分和晶体结构.用热失重方法测得多孔磁性高分子微球中磁性物质的含量可达26.7%.     

带孔壳聚糖微球的制备及其释药性研究

利用交联法制备了多孔壳聚糖微球,并借助扫描电镜观察了其物理形貌,考察了多孔载药微球的缓释性能。实验结果表明,制备的微球具有多孔结构且微球的药物缓释效果较好,其中释药速率随投料比增加和微球粒径的减小而增加,并且在酸性环境中由于壳聚糖微球的溶胀行为药物释药速率加快。     

磁性高分子微球制备研究进展

磁性高分子微球作为一种新型功能材料,具有强磁响应性、易生物降解、生物相容性好、无毒、可通过其他手段进行友好改性等特性。介绍了近年来磁性高分子微球的制备方法,对各种方法进行了简要分析,指出不同的制备方法可以制备出具有不同性能的磁性高分子微球。最后对磁性高分子微球的制备方法的发展趋势进行了展望。     

亲水性高分子磁性微球的合成和应用研究

对近年来国内外有关亲水性高分子磁性微球的研究成果和发展现状进行了综述,具体讨论了包埋法、单体聚合法及原位法等常用的合成制备方法及其优缺点,指出反相(微)乳液聚合是制备亲水性聚合物微球的有效方法。分析了亲水性高分子磁性微球在酶固定化和实现靶向给药等方面的应用及存在的问题,对磁性微球的发展前景进行了展望。     

微球中替莫唑胺含量测定方法的研究

随着对纳米靶向载药微球的重视,目前对纳米载药微球的研究也越来越多,但由于在制备过程工艺、药物种类、性质等的不同,给微球中药物含量的测定带来一定的困难,也很难形成统一的方法对载药微球中的药物含量进行测定,本实验结合自身工艺和药物性质,介绍一种间接测定微球中替莫唑胺含量的方法,通过验证,说明本方法具有较好的可行性和便捷性。     

药物偶联亲和高分子微球对牛血蛋白吸附性能研究

在制备亲和高分子乳液微球基础上,对其进行空间臂改性和药物分子偶联制得PSGN-MTA亲和高分子微球药物。为研究亲和高分子微球生物相容性,考察了高分子微球药物在缓冲液中药物释放行为及对BSA蛋白吸附能力。结果表明,亲和微球表面化学键合MTA药物浓度较高且分布均匀时,对BSA蛋白的吸附过程较符合一级动力学方程。还考察了pH值对BSA蛋白吸附的影响,中性条件时PSGN-MTA微球对于BSA吸附效果较好。     

微球中替莫唑胺含量测定方法的研究

随着对纳米靶向载药微球的重视，目前对纳米载药微球的研究也越来越多，但由干在制备过程工艺、药物种类、性质等的不同，给微球中药物含量的测定带来一定的困难，也很难形成统一的方法对载药微球中的药物含量进行测定，本实验结合自身工艺和药物性质，介绍一种间接测定微球中替莫唑胺含量的方法，通过验证，说明本方法具有较好的可行性和便捷性。     

氨基化PGMA高分子微球的应用及制备研究进展

PGMA(聚甲基丙烯酸缩水甘油酯)微球是一种富含大量环氧基的功能高分子材料,既具备良好的化学反应性能,又有特定的物理结构;并且经过氨基化的PGMA高分子微球可以作为吸附剂附剂多种物质,在不同的条件下可以只针对一种物质进行识别吸附,使得氨基化的PGMA高分子微球在各个方面的应用需求大幅度增加。下面将对氨基化PGMA高分子微球的应用领域及制备方法进行论述。     

磁性生物高分子微球的研究

生物高分子磁性微球是一种新型功能材料,在化工、生物工程、生物医学等许多方面有良好的应用前景。对磁性高分子微球的研究进展进行了综述,介绍了各类微球的制备方法及相关原理,并对磁性高分子微球的未来研究方向进行了展望。在此基础上,概述了生物高分子磁性微球的结构、性质及在固定化酶、靶向药物、细胞分离与免疫分析等领域的应用。     

泡沫相相分离制备多孔聚合物微球连续化工艺

采用在泡沫相进行溶剂挥发的方法，连续、高效制备聚甲基丙烯酸甲酯-丙烯酸丁酯[P(MMA-BA)]共聚物多孔微球。采用自制的连续化反应装置，在一定搅拌速率和反应温度下，向反应器连续加料，在出口处连续收集溢出的泡沫并进行消泡、分散，再经洗涤、过滤、干燥得到多孔聚合物微球。重点研究了油相进料速率、反应温度、搅拌速率、聚乙烯醇用量(PVA浓度)对平均泡沫溢出速率、微球收率、微球粒径以及多孔形态的影响规律。结果表明：在反应温度为45℃，搅拌速率为500 r/min，油相溶液进料速率为30 g/min，PVA浓度为1.0%(质量)，油相溶液中P(MMA-BA)∶二氯甲烷(DCM)∶正庚烷(HT)=10∶53∶6(质量比)的工艺条件下，聚合物微球的收率高达92%，平均粒径为130 μm，P(MMA-BA)微球球形饱满，呈多孔结构。     

Formulating Drug Delivery Systems by Spray Drying

The knowledge of the potential use of the spray-drying technology to prepare microparticulate drug delivery systems—microspheres and microcapsules—has been strongly improved over the last years. Various microparticulate spray drying systems used as vehicles for drug encapsulation and delivery that have been investigated for different purposes are presented here, including spray-dried powders formulated with hydrophilic polymers allowing controlled drug release, biodegradable microspheres prepared from aqueous systems, and spray-dried silica gel microspheres.     

基于纤维素模板的聚合物空心微球作为药物载体的性能研究及分析

以羟丙基纤维素为模板材料,分别采用不同的聚合方法制备了2种不同形态和结构的聚合物空心微球--聚N-异丙基丙烯酰胺-co-聚丙烯酸(PNIPAm-co-PAA)微凝胶和聚N-异丙基丙烯酰胺-聚丙烯酸(PNIPAm-PAA)水凝胶微囊。以盐酸阿霉素(Dox)作为模型药物,考察了聚合物空心微球作为药物载体的载药能力和体外释放性能。研究表明,PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊和Dox分子能够通过正负电荷的相互吸引实现有效结合;载药微球具有良好的缓释性能,并对Dox的释放表现出明显的pH值敏感性和温度敏感性。体外细胞毒性实验表明,载药PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊具有很高的抗肿瘤活性,细胞相对存活率均可达20%左右。PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊在作为水溶性药物或蛋白类药物载体方面,具有潜在的应用价值,同时有望应用于木材胶黏剂防腐等。     

生物降解聚合物药物微球的制备方法

综述了近年来生物降解聚合物药物微球的制备方法。随着药剂学的不断发展,传统的载药体系已经不能满足其需求。因此出现了许多新型的具有不同功能特性的药物载体。生物降解聚合物微球由于其结构组成可设计,并具有良好的安全性、生物相容性和生物降解性,可用作药物控释载体、表面改性、支架材料等,在生物医学领域获得了广泛的重视和应用。     

Fabricating colloidal crystals and construction of ordered nanostructures

Colloidal crystals of polymeric or inorganic microspheres are of extensive interest due to their potential applications in such as sensing, optics, photonic bandgap and surface patterning. The article highlights a set of approaches developed in our group, which are efficient to prepare colloidal crystals with ordered voids, patterned colloidal crystals on non-planar surfaces, heterogeneous colloidal crystals of different building blocks, colloidal crystals composed of non-spherical polyhedrons, and colloidal crystals of non-close-packed colloidal microspheres in particular. The use of these colloidal crystals as templates for different microstructures range from nanoscale to micron-scale is also summarized.     

Preparation and characterization of porous crosslinked microspheres of new aromatic methacrylates

The aim of this work was to prepare a new group of aromatic methacrylate monomers, utilise them in preparation of porous microspheres and study the influence of their chemical structure on the textural properties of porous methacrylate microspheres. Polymeric microspheres were prepared by suspension-emulsion polymerisation of four aromatic monomers: methacryloiloxybenzene, 1,2-dimethacryloiloxybenzene, 1,3-dimethacryloiloxybenzene and 1,4-dimethacryloiloxybenzene with another crosslinking agent—trimethylolpropane trimethacrylate. Mass median diameters of obtained beads are in the range 22–35 μm. The polymerisation reactions were carried out in the presence of a pore forming diluent. The influence of the diluent system on the porous structure of microspheres was studied in detail. To determine the textural properties of the studied microspheres, nitrogen adsorption–desorption and inverse sized exclusion chromatography measurements were used. Specific surface area of the obtained microspheres achieves value from 185 to 510 m²/g. Since obtained polymeric materials can be used as chromatographic packings for HPLC their porous structure in a swollen state was investigated. Significant differences in the porous structure parameters for dry and swollen microspheres were observed.     

开孔型聚合物微发泡材料研究进展

通过回顾目前几种微孔材料成型的主要方法,介绍了微发泡成型技术用于制备开孔型微孔材料的必要性。讨论了关于开孔型聚合物微发泡材料制备技术及研究方法的几种思路,分别是不相容聚合物共混、泡孔合并模型、熔融挤出发泡、开孔剂法和气体浓度阈(值)等方法,这些方法的微孔成型机理各不相同,所制备的材料微观结构也各有特点。文献分析表明:微发泡成型方法用于开孔型微孔材料的制备是一种非常有前景的技术。     

Span 60 as a Microsphere Matrix: Preparation and in Vitro Characterization of Novel Ibuprofen-Span 60 Microspheres

Microspheres are a potential delivery system for controlled and sustained drug release. Polymeric microspheres are commonly prepared by the solvent evaporation technique whereas waxy microspheres by the melt dispersion technique. The goal of this study was to prepare a surfactant (Span 60)—Ibuprofen microspheres using both techniques. Ibuprofen‐Span 60 microspheres were fabricated with different drug to polymer weight ratios of 3:1, 1:1 and 1:3 and characterized by particle size, in vitro dissolution, infrared spectroscopy, x‐ray diffraction and scanning electron microscopy. The actual drug content increased with increasing the concentration of anti‐aggregating agent (polyvinylpyrolidone). The actual drug content and drug encapsulation efficiency was markedly higher in case of microspheres prepared by a solvent evaporation technique compared to that prepared by a melt dispersion one using the same theoretical drug content. The microspheres were spherical with irregular surfaces. The in vitro release showed no burst effect and incomplete drug release. The rate and total drug released from the microspheres prepared by a solvent evaporation technique are higher than those prepared by using the melt dispersion technique. FTIR rolled out the chemical changes of the drug in Span 60 microspheres. The X‐ray diffraction pattern of the microspheres prepared by using a solvent evaporation technique showed a decrease in the drug crystallinity. The drug crystallinity in microspheres prepared by the melt dispersion technique decreased with increasing the theoretical drug content. The drug entrapment mechanism is responsible for the changes in drug physicochemical properties and in vitro release.     

Fabrication and surface characterization of electrosprayed poly(L‐lactide) microspheres

Electrospraying is a one‐step technique for fabricating polymeric microspheres/nanospheres, and the surface characterization of polymeric microspheres fabricated under high voltage is different from an emulsion method. In this study, biodegradable poly(l ‐lactide) (PLLA) microspheres were successfully fabricated by electrospraying, and electrospraying parameters were used to investigate the size and ζ potential of the electrosprayed PLLA microspheres. The results demonstrate that electrospraying was a one‐step method for fabricating monodispersed PLLA microspheres with a size of 1.92 ± 0.35 μm and that the enrichment of methyl groups on the surface of the microspheres contributed to the strong hydrophobicity of electrosprayed PLLA microspheres. Of all the electrospraying parameters investigated, the size and ζ potential of the PLLA microspheres increased with increasing solution concentration and flow rate and decreased with increasing injection voltage and collecting distance. The results provide a theoretical basis for preparing electrosprayed polymeric microspheres as drug carriers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Tamoxifen‐loaded microspheres based on mixtures of poly(D,L‐lactide‐co‐glycolide) and poly(D,L‐lactide) polymers: Effect of polymeric composition on drug release and in vitro antitumoral activity

Mixtures of different bioerosionable polyesters were used to prepare microparticulated tamoxifen delivery systems to achieve anticancer effects in breast malignant cancer cells. Tamoxifen (TMX) was included into microspheres (MS) formulated via spray‐drying. Mixtures of poly(D ,L ‐lactide‐co‐glycolide) (PLGA) of different lactide/glycolide proportions (50 : 50 and 75 : 25) and poly(D ,L ‐lactic acid) (PLA) were used. The average diameter of the resultant TMX‐loaded microparticles was in the range 1.04 ± 0.51–1.55 ± 0.95 μm. The encapsulation efficiency of TMX was between 97.8% [48.9 ± 0.1 TMX (μg)/MS (mg)] and 69.6% [36.6 ± 0.1 TMX (μg)/MS (mg)] depending on the polymeric composition of the formulation. Drug burst effect was not observed. TMX was released from the polymeric matrices in a sustained release manner between 11 and 58 days depending on polymeric composition of microspheres. TMX‐loaded microspheres showed high efficacy in causing cell death in MCF7 breast malignant cancer cells. Thus, these TMX‐loaded PLGA‐based microspheres hold potential to treat breast malignant cancer cells. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012