可降解聚合物包覆次血红素六肽微球的制备及生物活性

采用水包油包水(W₁/O/W₂)复乳溶剂挥发法制备了包覆次血红素六肽(DhHP-6)的2种聚酯微球. 通过扫描电子显微镜、 体外缓释行为、 高效液相(HPLC)检测、 酶活力测定和初步的动物实验等表征, 综合评价了载药微球的体外释放及体内生物活性. 实验结果表明, 载药微球球体圆整, 粒径分布均匀, 载药量高, 能够实现体外缓释, 并对细胞过氧化损伤和小鼠脑缺血损伤均有一定的保护作用.     

Acyclovir-Loaded Chitosan Microspheres for Gastroretention: Development and Evaluation

Mucoadhesive chitosan microspheres of acyclovir were prepared to prolong the gastric residence time using simple emulsification phase separation technique. The particle morphology of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (31.62 ± 4.64). The entrapment efficiency was found to be in the range of 40.24 to 67.29%. The concentration of the glutaraldehyde (25%v/v) as a cross-linker 2 ml and drug polymer ratio of 1:2 caused an increase in the entrapment efficiency and the extent of drug release. The optimized chitosan microspheres were found to possess good bioadhesion (79.89 ± 1.01%). The gamma-scintigraphy study showed the gastric residence time of more than 6 hours which revealed that optimized formulation could be a good choice for gastroretentive systems.     

作为细胞微载体的明胶基缓释微球的制备

用改良的乳化冷凝法制备载牛血清蛋白(BSA)的大粒径明胶微球. 结果表明, 明胶水溶液的质量分数为25%、水相与油相体积比3∶20、搅拌速度300 r/min、交联剂用0.1 mL质量分数为25%的戊二醛、 表面活性剂用0.1 g span-80为制备平均直径约250 μm明胶微球的理想条件. 所制备微球的后处理方法不同, 则明胶微球的表面形貌也不同, 细胞粘附率不同. 空白明胶微球在体外可以完全降解, 载BSA的明胶微球对BSA具有良好的缓释性, 释放时间可长达30 d. 显微镜观察成纤维细胞在明胶微载体上生长良好.     

聚L-谷氨酸担载胰岛素口服微球的制备与评价

以聚L-谷氨酸为载体材料, 采用无水乳液法制备了口服胰岛素微球, 微球直径在5~20 μm, 载药质量分数为5%~9%. 载药微球具有良好的pH敏感释放行为, 在胃模拟液中2 h释放量约为5%, 在肠道模拟液中2 h释放90%以上. 考察聚合物分子量、溶液浓度、理论投药量及混合材料对微球释放行为的影响.     

淫羊藿苷壳聚糖/明胶微球的制备及其体外释放研究

本试验以壳聚糖、明胶为载药基质,以中药淫羊藿苷为模拟药物,通过乳化交联的方法制备淫羊藿苷/壳聚糖/明胶微球。考察微球的理化特性,建立持续流动释放系统,检测了微球的体外释放特性和影响因素。微球的理化特性受工艺条件如搅拌速度、乳化剂用量、交联剂用量等因素影响。微球的体外释放速率与微球的粒径、交联度负相关,与载药量正相关。试验结果表明,壳聚糖、明胶可作为缓释微球的载体基质,微球制备工艺简单稳定,微球的释放速率可控,淫羊藿苷/壳聚糖/明胶微球是一种良好的药物释放体系。     

Encapsulation and characterization of flurbiprofen loaded poly(є-caprolactone)–poly(vinylpyrrolidone) blend micropheres by solvent evaporation method

Flurbiprofen loaded PCL/PVP blend microspheres were prepared by o/w solvent evaporation method using various concentrations of gelatin as emulsifying agent. Microsphere recovery decreased with a decrease in the concentration of the emulsifier in the dispersion. Encapsulation efficiency and drug loading of microspheres increased with decrease in concentration of emulsifying agent. Hydration rate, encapsulation efficiency and drug loading of microspheres increased with increase in concentration of PVP. Rheological properties showed free flowing nature of microspheres. SEM (Scanning electron microscope) revealed microspheres were discrete, spherical and became porous with decrease in concentration of emulsifying agent but smooth with higher concentration of emulsifying agent. FTIR (Fourier transform infrared spectroscopy) spectra of pure and encapsulated flurbiprofen in all formulation showed no significant difference in characteristic peaks, suggesting stability of flurbiprofen during encapsulation process. X-RD (X-ray powder diffractometry) of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating dispersion at molecular level and hence decrease in the crystallinity of drug in microspheres. Microspheres showed an enteric nature at pH 1.2 and a sustained release pattern at pH 6.8. Rapid drug release was observed in microspheres with higher concentration of PVP (polyvinylpyrrolidone), PVP acts as channeling agent. Formulation with low concentration of emulsifying agent also showed a fast release due to porous structure. Drug release kinetics followed zero order at pH 1.2 while at pH 6.8 Higuchi model was best fitted and was found non fickian.     

Preparations and properties of drug-eluting embolization microspheres based on modified gelatin

Embolization using microspheres plays an important role in interventional cancer therapy. The drug-eluting embolization microspheres were prepared via reverse suspension crosslinking of gelatin, followed by modification of the cross-linked microspheres. The microspheres displayed regular spherical shapes with size distribution ranging from 180 μm to 350 μm. The negatively charged groups (COO^?) were introduced into the microspheres which could load positively charged doxorubicin with loading rates as high as 26.1% and 34.0% in 1 and 12 h, respectively. The high drug-loading rates were ascribed to ionic interaction between carboxyl groups and doxorubicin. The drug release profile showed the modified microspheres (MMS) have a sustained release manner compared with non-MMS in phosphate buffered saline (PBS). The MMS were almost completely degradated after 20 days. Cytotoxicity assay certified that the MMS were non-cytotoxic, and could be potentially used as biocompatible materials.     

Biomimetic gelatin-octacalcium phosphate core-shell microspheres

Calcium phosphate/polymeric microparticles synthesized through a biomimetic approach are regarded with increasing interest for their various potential applications, including tissue engineering and regenerative medicine. Herein we report the synthesis and characterization of gelatin/octacalcium phosphate core/shell microspheres. Deposition of the calcium phosphate shell on the polymeric microspheres was obtained through bio-inspired mineralization on the surface of functionalized gelatin microparticles. Gelatin microspheres stabilized by alginate dialdehyde were prepared using an inverse microemulsion. Functionalization was achieved by enriching the microspheres composition with calcium ions or, alternatively, with alendronate, a bisphosphonate widely employed for the treatment of bone diseases. Functionalization and synthesis of the inorganic phase in the microemulsion environment were key factors for the achievement of a complete coating of the microspheres with calcium phosphate. The inorganic shell is constituted of small crystals of octacalcium phosphate, which control gelatin and alendronate release.     

Preparation and characterization of three types of cefquinome-loaded microspheres

The polymers of poly (lactic-co-glycolic acid), gelatin, and ethyl cellulose were used to control the microscopic structure of microspheres prepared by spray drying. We investigated controlled release by varying material concentrations, sprayer inlet temperatures and air velocities, and optimized process parameters of yield, particle size, and distribution. Three types of polymeric microspheres with a mean particle size range of 13–25?µm were loaded with cefquinome and characterized. In vitro drug release studies determined that microspheres were the most suitable structures for controlling release due to their high entrapment capacities and release times greater than 24?h.     

131I标记海藻酸钠包裹明胶微球的制备及性能评价

建立了明胶微球和海藻酸钠(SA)包裹微球的制备方法,并通过实验比较了明胶微球和包裹微球的各种特性,最后用氯胺T法将125I及131I分别标记在微球上.结果表明,包裹微球对碘有更高的负载量和稳定性;在相同条件下,包裹微球的降解时间比明胶微球的降解时间长;将标记后的明胶微球通过直接注射介入到新西兰大白兔的肝脏,采用发射单光...     

PLA/MSM缓释微球的制备及生物活性

采用膜乳化-液中干燥法制备出担载二甲基砜(MSM)的聚乳酸(PLA)微球(PLA/MSM), 并研究了膜孔径、 搅拌转速和MSM浓度对载药微球形貌、 尺寸、 载药量、 体外释放及细胞活性的影响; 采用场发射环境扫描电子显微镜(ESEM)观察微球形貌、 尺寸及分布, 用等离子体发射光谱(ICP-AES)法检测PLA/MSM微球载药量、 包封率及体外释放, 采用ESEM观察微球内部结构, 并通过体外细胞培养和噻唑蓝(MTT)法检测MC-3T3-E1细胞的增殖能力. 研究结果表明, 膜乳化法制备的载药微球规整, 呈典型的圆球状, 表面光滑, 内部有多孔结构. 当膜孔径为5.1 μm且搅拌转速为500 r/min时, PLA/MSM微球大小更为均一; 当体系中MSM质量分数为8.6%时, 载药量可达到77.43%. 随着膜孔径减小及药物浓度的增加, 体外释放速率加快, 但初期均无明显的突释现象, 约10 d后累积释放量达到89.2%. 细胞实验结果显示, 在膜孔径为5.1 μm且MSM质量分数为8.6%的条件下, 制备的载药微球在细胞培养7 d时表现出明显的促增殖作用.     

多孔磁性明胶微球的制备与结构表征

首先通过乳化法得到磁性明胶微球, 然后在高速搅拌条件下向乳液中直接加入正硅酸乙酯(TEOS), 制备出多孔磁性明胶微球. 用SEM, TEM观察了微球的微观形貌, 发现微球呈疏松多孔状结构. 用FT-IR, TGA, VSM等测试手段对微球的结构和性能进行表征. 结果表明, 二氧化硅掺杂于磁性明胶微球中. TEOS在反应中作为明胶微球的交联固化剂, 推测其固化机理是物理交联固化. 实验证实二氧化硅改性后, 磁性明胶微球内部磁性颗粒氧化速度有所降低. 所得到的多孔磁性明胶微球表现出铁磁性.     

载药微球释放规律的实验研究

磁性载药微球是将药物与磁性物质共同包埋于微球载体中,在外界磁场的作用下到达并固定在病变部位,使所含药物得以定位释放,从而达到高效、速效、低毒的新型药物制剂。是目前的一个热门研究课题,明胶微球具有生物可降解性,可以口服或注射［１］。我们以明胶为载体,以...     

Insulin-carrying microspheres, in vitro studies.

Loading and release characteristics of insulin-carrying albumin and starch microspheres have been studied in vitro. The sorption characteristics of 125I-labelled insulin onto albumin microspheres were studied and were found to be completed within 5h, and the loading capacity was found to be 0.14% w/w. Insulin did not show any sorption into the matrix of the starch microspheres. The release characteristics were analyzed by high performance liquid chromatography. About 80% was released within 5-10 min from albumin microspheres and starch microspheres, respectively.     

接枝微球CPVA-g-PSSS的制备及其对5-氟尿嘧啶载药及体外结肠定位释药特性研究

在具有生物相容性的交联聚乙烯醇(CPVA)微球表面,采用铈盐-羟基氧化还原引发体系,实施了对苯乙烯磺酸钠(SSS)的表面引发接枝聚合,制得了接枝有聚阴离子的接枝微球CPVA-g-PSSS,采用红外光谱(FTIR)、扫描电子显微镜(SEM)及zeta电位测定等法,对接枝微球的化学结构及物理化学特性进行了表征.在此基础上重点考察分析了接枝微球CPVA-g-PSSS对5-氟尿嘧啶(5-FU)的吸附(载药)性能与吸附机理,考察探索了载药微球在不同pH介质中的释放行为.实验结果表明,羟基-铈盐氧化还原引发体系可有效地引发SSS在CPVA微球的表面接枝聚合,在适宜的反应条件下,可制得PSSS接枝度为16.1 g/100g的接枝微球CPVA-g-PSSS.在酸性介质中,受强静电相互作用的驱动,接枝微球CPVA-g-PSSS对5-FU分子表现出很强的吸附能力,吸附容量达105 mg/g,可实现有效载药.载药微球的释药行为具有强烈的pH依赖性,在pH=1的介质中,基本不释药;而在pH=7.4的介质中,则发生突释,表现出良好的结肠定位释放行为.     

ZnS微米球的水热合成及光催化性能研究

以L-半胱氨酸为硫源,明胶作为组装剂,采用水热方法制备了粒径均一的ZnS微米球。利用XRD,TEM,FESEM,FTIR探讨了明胶、反应时间和反应温度对产物形貌和尺寸的影响,其结果表明ZnS微米球是由ZnS纳米颗粒组装而成的3D多级结构。光催化性能研究表明,明胶的加入提高了最终产物的光催化性能。利用产物的荧光发光性能解释了其光催化性能产生差异的原因。     

The influence of chitosan on in vitro properties of Eudragit RS microspheres

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.     

基于天然高分子基元的阻隔层对磁性载药聚乳酸微球的控释作用

利用层层组装技术构建了基于天然高分子壳聚糖和海藻酸钠的阻隔层, 并研究了该阻隔层对磁性载药聚乳酸微球的药物释放作用. 实验结果表明, 阻隔层能够有效抑制模型药物的突释, 具有延缓药物释放的效果. 具有阻隔层的磁性载药体系具有药物释放平缓和生物相容性高等特点, 是理想的磁靶向载药体系.     

pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate: swelling kinetics and drug delivery properties

Porous chitosan (CS) polyelectrolyte complex (PEC) hydrogel microspheres were prepared via either wet phase-inversion or ionotropic crosslinking with sodium tripolyphosphate (Na+ - TPP) and dextran sulfate (DS). The resulting microspheres were characterized using scanning electron microscopy (SEM) and elemental analysis (EA). The controlled release behavior of ibuprofen (IBU) from these microspheres was investigated. The PEC microspheres were about 700-950 microm in diameter with large pores and open porous structure. The CS/TPP/DS microspheres resisted hydrolysis in strong acid and biodegradation in enzymatic surroundings. The swelling kinetics for CS microspheres was close to Fickian diffusion, whereas those for CS/TPP and CS/TPP/DS were non-Fickian. Furthermore, the equilibrium water content (EWC) and water diffusion coefficient (D) increased with the pH of the media. The release profiles of IBU from CS/TPP/DS microspheres were slow in simulated gastric fluid (SGF, pH 1.4) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 6 h after changing media. Overall the results demonstrated that CS/TPP/DS microspheres could successfully deliver a hydrophobic drug to the intestine without losing the drug in the stomach, and hence could be potential candidates as an orally administered drug delivery system.     

Preparation, characterization, and application of multistimuli-responsive microspheres with fluorescence-labeled magnetic cores and thermoresponsive shells

Novel functional microspheres with multistimuli-responsive properties have been prepared and characterized. The as-prepared microspheres respond to an external magnetic field, environmental temperature, and ultraviolet radiation. The in vitro drug-loading efficiency and drug-release behavior of these microspheres demonstrated that they could be used as drug carriers for drug controlled release. The results of in vivo distribution investigations of these microspheres showed that they exhibit a high magnetic-targeting effect, which holds promise for applications in various fields such as magnetic drug targeting and tissue labeling, among others.