Distribution of Etoposide-Loaded Hydrophilic Albumin Microspheres in Mice

Abstract

Hydrophilic albumin microspheres of etoposide were prepared by the emulsion polymerization technique using glutaraldehyde as the cross-linking agent. The microspheres prepared had a mean diameter of 1.5 μm. The microspheres were injected into mice by the intravenous route. In all, 12 mice were selected for the study, out of which 10 were given the drug-loaded microspheres and 2 were kept as solvent control. The mice were sacrificed after 24 hr and the accumulation of drug was determined in lungs, liver, and kidney.     

表面可修饰的荧光复合微球的制备及表征

采用反相悬浮乳液法合成了丙烯酸(AA)含量不同的N-异丙基丙烯酰胺(NIPAM)共聚丙烯酸(AA)的聚合物模板P(NIPAM-co-AA), 以此作为微反应器, 分别用两种不同的方法制备了P(NIPAM-co-AA)-co-Alq3 (八羟基喹啉铝)荧光复合微球, 再用四乙氧基硅烷(TEOS)对其表面进行修饰, 获得了表面功能化的P(NIPAM-co-AA)-Alq3-SiO₂荧光复合微球。用SEM、 IR、 FM和XRD等手段对其结构和性能进行表征。结果表明: 所制备的荧光复合微球单分散性好、 荧光发光效率较高且性能稳定, 同时具有较大的比表面积; 功能化的荧光复合微球可用于高通量药物筛选和识别生物大分子等生物医学领域。      

壳聚糖微球的季铵化及其抗菌性能的研究

采用乳化交联法制备了壳聚糖微球,并对其进行季铵化表面改性。实验分别考察了溶剂、反应时间和季铵化试剂C_4H_9Br与壳聚糖微球物质的量之比对季铵化壳聚糖微球的影响。研究结果表明,壳聚糖微球在乙腈溶液中分散较好,反应时间为12h,季铵化试剂与壳聚糖微球的物质的量之比为3∶1时,制备的季铵化壳聚糖微球效果较好。对壳聚糖、壳聚糖微球、季铵化壳聚糖微球进行抗菌性能测试,发现其抗菌性能的强度大小依次为:季铵化壳聚糖>壳聚糖微球>壳聚糖,其中季铵化壳聚糖微球的抑菌率为52.1%。     

高效光催化降解气相苯纳米TiO2微球的制备EI北大核心CSCD

以四氯化钛为钛源,尿素为沉淀剂前驱物,硫酸钠为分散剂,利用水热法在水-醇体系中制备出纳米TiO2微球。运用X射线衍射、电子显微镜、N2吸附-脱附和紫外-可见光谱等手段表征样品的结构和性质,并考察了水热温度对纳米TiO2微球结构及光催化降解气相苯活性的影响。结果表明,此类微球由纳米颗粒组成,且比表面积大,介孔结构明显,光吸收出现明显的“蓝移”。光催化结果显示,微球具有很高的光催化活性,尤其是180℃下制备的微球仅用20min将苯完全去除,但生成CO2的量仍随时间有所增加,表明微球的强吸附性能促进其光催化降解过程,且矿化率高达5.5,是P25(2.7)的2倍。     

Gd_2O_3空心微球的制备及Gd_2O_3/丁基橡胶复合材料低频阻尼性能

以分散聚合法制备的聚苯乙烯(PS)微球作为模板,通过均相沉淀法制备前驱体PS-Gd(OH)CO_3复合微球,高温煅烧后得到Gd_2O_3空心微球,将其与丁基橡胶复合制备低频高阻尼Gd_2O_3/丁基橡胶复合材料。采用FTIR、SEM、TEM分析、TG分析仪、XRD分析和XPS对Gd_2O_3空心微球的形貌与结构组成进行表征。将Gd_2O_3空心微球与粉体分别作为填料加入丁基橡胶中制备Gd_2O_3/丁基橡胶复合材料。结果表明:Gd_2O_3空心微球由立方萤石结构的颗粒组成,外空心直径为0.9μm,壳层厚度约为100nm;添加空心微球的复合材料阻尼性能较好;与纯丁基橡胶相比,Gd_2O_3/丁基橡胶复合材料的低频阻尼性能明显提高。     

双马来酰亚胺交联单分散聚苯乙烯微球的制备及表征

采用分散聚合法,以苯乙烯为单体,二苯甲烷双马来酰亚胺(BDM)为交联剂,制备了单分散交联聚苯乙烯微球(St/BDM)。研究了分散聚合反应中单体(St)、引发剂(AIBN)、分散剂(PVP)、交联剂(BDM)用量对微球粒径和粒径分布的影响。通过优化反应条件,合成了平均粒径为3.03μm(ε=0.05)的单分散交联聚苯乙烯微球。热稳定性分析和耐溶剂性实验结果表明,二苯甲烷双马来酰亚胺(BDM)交联的聚苯乙烯微球热稳定性和耐溶剂性能比线性的聚苯乙烯微球有了很大的提高。当失重5%时,聚合物的热分解温度由交联前的306℃上升到交联后的328℃。     

PLLA-PEG-PLLA/Fe_3O_4磁性微球的制备及性能

以聚乙二醇为引发剂,L-丙交酯为单体,开环聚合得到聚乳酸-聚乙二醇三嵌段共聚物(PLLA-PEG-PLLA),采用溶剂挥发法制备了PLLA-PEG-PLLA/Fe_3O_4磁性微球,并通过扫描电镜对其形态进行了表征。利用振动样品磁强计和Tg研究了微球的磁含量和磁性能,结果发现,相同粒径不同磁含量的磁性微球,磁含量越高,升温速率越快,当磁含量为70.57%时,升温速率最快,能达到磁热疗的有效温度42℃。对于磁含量相同,粒径不同的微粒,粒径越小,升温速率越快,粒径约为10μm时升温速率最快。     

Cyclophosphamide Loaded Albumin Microspheres: Liver Entrapment and Fate in Mice

Abstract

Microspheres offer the possibility of target selectivity through choice of appropriate size or surface charecteristics, slow release of drug and also minimize systemic toxicity. The active substance of this investigation, cyclophosphamide (CP), interferes with the growth of cancer cells which are eventually destroyed. Since side effects of CP are frequently dose related, by incorporating low dose of CP to human serum albumin (HSA) microspheres, the normal body cells are not affected while the tumour cells are destroyed.

Cyclophosphamide microspheres were prepared by the modification of the method of Scheffel et al and Gürkan et al. 2,3-butanedione was used as a cross-linking agent. The albumin microspheres containing CP were labelled by ^99mTc by incorporating SnC1₂.2H₂0 at a concentration of 5% of the matrix material. All the microspheres used in this study ranged between 1–5 μm.

A suspension of ^99mTc labelled cyclophosphamide microspheres was injected into swiss albino mice intravenously. At 15 min, 30 rain, 6 h and 24 h mice were killed and the organs assayed for radioactivity accumulated in each organ. 1 hour later the radioactivity in the liver increased to 4.73 percent. By 24 hours, 2.68 percent of the radioactivity was found in the liver. Whereas the percentage of free cyclophosphamide at 1 and 24 hours was 2.22 and 2.57 percent, respectively. Based on the evidence obtained from these results, the application of CP loaded HSA microspheres seems advantages in accumulation in liver.     

煅烧温度对TiO_2中空微球光催化性能的影响

以分散聚合法制得的单分散阳离子聚苯乙烯（PS）微球为模板,钛酸丁酯为前驱体,采用溶胶-凝胶法在模板表面包覆TiO2壳层,并在不同煅烧温度下制备了晶相结构不同的微米级中空TiO2微球。采用TEM、SEM、FT-IR、XRD、UV-Vis DRS对样品的微观结构、相态组成及光催化性能进行了表征。结果表明TiO2中空微球平均粒径达到1.23μm,壳层厚度约为30nm;随着煅烧温度增加,锐钛矿晶粒尺寸会增加,并在700℃时出现混晶结构;在500℃煅烧得到的TiO2中空微球对甲基橙（MO）降解表现出比P25更好的光催化性能及光催化稳定性。     

pH dependent hydrolysis and drug release behavior of chitosan/poly(ethylene glycol) polymer network microspheres

Semi-interpenetrating polymer network (IPN) microspheres of chitosan and poly(ethylene glycol) PEG were prepared for controlled release of drugs. A new method for the chemical crosslinking of chitosan microspheres containing isoniazid (INH) as a model drug is proposed and evaluated. The method consists of the exposure of microspheres to the vapor of crosslinking agent that act in gaseous phase under mild conditions. The structural analysis of the microspheres was carried out by FTIR-analysis. The swelling behavior, hydrolytic degradation, structural changes of the microspheres and loading capacity (LC) of the microspheres for INH were investigated. The prepared microspheres have shown 93% drug loading capacity, which suggested that these semi-IPN microspheres are suitable for controlled release of drugs in an oral sustained delivery system. © 2001 Kluwer Academic Publishers     

微波辐射分散聚合制备单分散聚苯乙烯微球

微波辐射代替传统加热方法,进行苯乙烯分散聚合,制备拉径大小在200nm-500nm之间,且为单分散的聚苯乙烯微球;探讨了单体、稳定荆、引发荆的浓度对微球粒径大小和分布的影响。研究结果表明,微波辐射分散聚合制备的聚苯乙烯微球拉径,小于常规加热分散聚合制备的微球粒径,且微波辐射制得的微球单分散性更好。     

苯乙烯/甲基丙烯酸共聚微球的制备及其性能表征

以苯乙烯(St)为单体,甲基丙烯酸(MAA)为功能单体,采用无皂乳液聚合方法制备了聚(苯乙烯-甲基丙烯酸)共聚微球。运用傅立叶红外光谱(FT-IR)、透射电子显微镜(TEM)、场发射扫描电镜(FE-SEM)、电势与纳米粒径分析仪等手段,对微球的组成成分、表面形貌、粒径及其分布、表面电势进行了表征。结果表明,微球粒径均匀,在100～200nm之间,球形度良好且呈单分散性,poly(St-MAA)共聚微球zeta电势为-37.2mV,MAA的亲水性基团和引发剂KPS的残基共同作用提高了共聚微球乳液的稳定性。     

无皂乳液聚合法制备单分散聚苯乙烯微球

以苯乙烯(St)为单体,过硫酸钾(KPS)为引发剂,采用无皂乳液聚合法制备了聚苯乙烯微球。研究了单体、引发剂的浓度,引发剂加入方式,聚合温度对制备PS微球粒径的影响。运用傅立叶红外光谱(FT-IR)、透射电子显微镜(TEM)、场发射扫描电镜(FE-SEM)、电势与纳米粒径分析仪等手段,对微球的组成成分、表面形态、粒径及其分布、表面电势进行了表征。结果表明微球粒径均匀,在100～200nm范围内,球形度良好且呈单分散性。     

Cellulose acetate microspheres as floating depot systems to increase gastric retention of antidiabetic drug: formulation, characterization and in vitro-in vivo evaluation

Gastric emptying is a complex process that is highly variable and makes the in vivo performance of drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug delivery systems for more than 12 hours utilizing floating or hydrodynamically controlled drug delivery systems. The objective of this investigation was to develop a floating, depot-forming drug delivery system for an antidiabetic drug based on microparticulate technology to maintain constant plasma drug concentrations over a prolonged period of time for effective control of blood sugar levels. Formulations were optimized using cellulose acetate as the polymer and evaluated in vitro for physicochemical characteristics and drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in healthy male albino mice. The shape and the surface morphology of the prepared microspheres were characterized by optical microscopy and scanning electron microscopy. In vitro drug release studies were performed and drug release kinetics were calculated using the linear regression method. Effects of stirring rate during preparation and polymer concentration on the size of microspheres and drug release were observed. The prepared microspheres exhibited prolonged drug release (more than 10 hours) and remained buoyant for over 10 hours. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 73% to 98% were obtained. The release rate decreased and the mean particle size increased at higher polymer concentrations. Stirring speed affected the morphology of the microspheres. This investigation revealed that upon administration, the biocompatible depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain orally given drug. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.     

大分子单体参与分散聚合制备功能性微球的研究

由于大分子单体具有特殊的结构和性质，它代替传统的稳定剂参与分散聚合，具有实验操作过程简便，制得微球表面洁净，粒径呈单分散性等优点。近年来，大分子单体已成为高分子科学研究的热点之一。文中对在分散聚合反应中采用大分子单体技术制备功能性微球的研究进行了综述。     

Multiparticulate Drug Delivery System for the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation

Biodegradable microspheres of poly(?)caprolactone were prepared by solvent evaporation method for controlled release of repaglinide. The prepared microspheres were spherical in shape having smooth surface. The average diameter was in the range of 24 to 31.04 µm. Drug entrapment efficiency of the prepared microspheres was in the range of 68.81% to 79.30%. Differential scanning calorimetry and x-ray diffraction analyses indicated the amorphous dispersion of drug in the microspheres. The drug release was continued up to 24 h depending upon the formulation variables; drug release was slow from the microspheres which were prepared with higher concentration of polymer and as the initial drug loading was increased, the drug release was also increased. A non-Fickian transport was the mechanism of drug release for all the microspheres. The in vivo anti-diabetic activity performed on steptozotocin induced rats indicated that the plain repaglinide has shown maximum percentage of reduction in blood glucose at the end of 3 h and then the percentage of reduction in blood glucose was decreased. While in case of rats treated with PCL5 microspheres, the percentage of reduction in glucose level was slow as compared to plain repaglinide within 3 h, but it was gradually increased to 74.86% at the end of 24 h.     

纳米晶氧化锌微球的制备

通过醋酸锌在一缩二乙二醇中热醇解反应制备了纳米晶ZnO微球,探讨了在醋酸锌热醇解法制备过程中升温速率对醇解反应温度和ZnO微球粒径分布的影响.在此基础上采用种子法制备了ZnO微球,考察了种子液加入量和反应时间对ZnO微球粒径分布的影响,并尝试使用SJN-30硅溶胶和SiO2微球乳液为种子液制备核-壳结构ZnO复合微球.     

In Vitro Evaluation of Albumin Microspheres Containing Actinomycin D

Albumin microspheres containing actinomycin D were prepared by the heat stabilization method. The compata-bility of the drug with magnetite and the optimum stability of the drug in different pH were studied. Drug loaded albumin microspheres containing magnetite showed good magnetic response. Release of the drug was slow and continued for 7 days exhibiting sustained release property. The difference as regards to the size, shape, drug content and release rate from freshly prepared and freeze dried drug loaded albumin microspheres was negligible.     

Development of novel interpenetrating network gellan gum-poly(vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.     

Development of Novel Interpenetrating Network Gellan Gum-Poly(vinyl alcohol) Hydrogel Microspheres for the Controlled Release of Carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.