二氧化钛接枝聚（苯乙烯-二乙烯苯）/马来酸酐多孔纳米复合微球的制备及表征（摘要）

中孔聚合物微球,由于具有大的比表面积、小的孔径和孔容,并有与外界环境介质相通的多孔孔道等特点而被应用于化妆品活性物和药物的缓释载体,以提高药物及化妆品活性物的安全性和使用效率.在早期的工作中,我们报道了聚苯乙烯-二乙烯苯[P（St-DVB）]多孔聚合物微球的制备及其在化妆品活性物缓释中的应用[4].[P（St-DVB）]多孔聚合物微球用于化妆品活性物的负载取得了较好的缓释效果,但是此种多孔聚合物微球在负载如Pasorl-1789类易光解的活性组分时,由于聚合物本身的透明性,当在紫外线等强光照射下,     

二氧化钛接枝聚(苯乙烯-二乙烯苯)/马来酸酐多孔纳米复合微球的制备及表征 二氧化钛接枝聚(苯乙烯-二乙烯苯)/马来酸酐 多孔纳米复合微球的制备及表征

中孔聚合物微球, 由于具有大的比表面积、小的孔径和孔容, 并有与外界环境介质相通的多孔孔道等特点而被应用于化妆品活性物和药物的缓释载体, 以提高药物及化妆品活性物的安全性和使用效率. 在早期的工作中, 我们报道了聚苯乙烯-二乙烯苯[P(St- DVB)]多孔聚合物微球的制备及其在化妆品活性物缓释中的应用[4]. [P(St-DVB)]多孔聚合物微球用于化妆品活性物的负载取得了较好的缓释效果, 但是此种多孔聚合物微球在负载如Pasorl-1789类易光解的活性组分时, 由于聚合物本身的透明性, 当在紫外线等强光照射下, 易光解的活性物就会发生分解, 最终导致失去活性作用, 因此纯的聚合物微球对易光解的活性物起不到良好的保护和缓释. 纳米二氧化钛由于具有良好的紫外吸收和折射能力及无毒等优点而广泛地应用于化妆品的物理防晒剂. 因此, 将纳米二氧化钛均匀地覆盖在多孔聚合物微球的表面可以在聚合物微球表面形成一道阻挡紫外线的屏障, 有效防止负载于多孔聚合微球内部的活性物的分解. 本文通过开环反应方法制备了二氧化钛接枝聚(苯乙烯-二乙烯苯)/马来酸酐中孔复合微球. 首先用氨基基团对纳米二氧化钛粒子表面进行修饰, 一方面防止其团聚, 另一方面使纳米粒子具有与聚合物微球产生共价键合的基团. 然后对多孔聚合物粒子表面进行马来酸酐修饰, 使其在保持原有的多孔形貌的基础上产生可与纳米粒子表面氨基开环反应的马来酸酐基团. 制得的多孔纳米复合微球经红外光谱、扫描电镜、透射电镜、X光衍射能谱及紫外分光光度计等表征, 结果表明, 纳米复合微球表面均匀地覆盖了纳米二氧化钛粒子, 复合粒子比纯聚合物粒子和未经修饰的二氧化钛粒子具有更好的紫外吸收效果. 将制得的复合微球用于对活性物Parsol 1789 (一种化妆品活性组分, 见光易氧化)的负载和缓释结果表明, 纳米复合多孔微球对负载于多孔网络中的活性物具有屏蔽紫外防止氧化和缓释作用.     

二氧化钛接枝聚(苯乙烯-二乙烯苯)/马来酸酐多孔纳米复合微球的制备及表征

中孔聚合物微球,由于具有大的比表面积、小的孔径和孔容,并有与外界环境介质相通的多孔孔道等特点而被应用于化妆品活性物和药物的缓释载体,以提高药物及化妆品活性物的安全性和使用效率.在早期的工作中,我们报道了聚苯乙烯-二乙烯苯[P(St-DVB)]多孔聚合物微球的制备及其在化妆品活性物缓释中的应用[4].[P(St-DVB)]多孔聚合物微球用于化妆品活性物的负载取得了较好的缓释效果,但是此种多孔聚合物微球在负载如Pasorl-1789类易光解的活性组分时,由于聚合物本身的透明性,当在紫外线等强光照射下,易光解的活性物就会发生分解,最终导致失去活性作用,因此纯的聚合物微球对易光解的活性物起不到良好的保护和缓释.纳米二氧化钛由于具有良好的紫外吸收和折射能力及无毒等优点而广泛地应用于化妆品的物理防晒剂.因此,将纳米二氧化钛均匀地覆盖在多孔聚合物微球的表面可以在聚合物微球表面形成一道阻挡紫外线的屏障,有效防止负载于多孔聚合微球内部的活性物的分解.本文通过开环反应方法制备了二氧化钛接枝聚(苯乙烯-二乙烯苯)/马来酸酐中孔复合微球.首先用氨基基团对纳米二氧化钛粒子表面进行修饰,一方面防止其团聚,另一方面使纳米粒子具有与聚合物微球产生共价键合的基团.然后对多孔聚合物粒子表面进行马来酸酐修饰,使其在保持原有的多孔形貌的基础上产生可与纳米粒子表面氨基开环反应的马来酸酐基团.制得的多孔纳米复合微球经红外光谱、扫描电镜、透射电镜、X光衍射能谱及紫外分光光度计等表征,结果表明,纳米复合微球表面均匀地覆盖了纳米二氧化钛粒子,复合粒子比纯聚合物粒子和未经修饰的二氧化钛粒子具有更好的紫外吸收效果.将制得的复合微球用于对活性物Parsol1789(一种化妆品活性组分,见光易氧化)的负载和缓释结果表明,纳米复合多孔微球对负载于多孔网络中的活性物具有屏蔽紫外防止氧化和缓释作用.     

新型含苯硼酸基团的两亲性共聚物微球的制备及其糖敏感性能

将3-丙烯酰胺基苯硼酸与马来酸酐改性β-环糊精反应, 合成了一种新型的共聚物, 并采用13C NMR, IR和UV-Vis等技术对共聚物的结构进行了表征. 利用SEM研究了聚合物在甲醇中的自组装形态. 通过在不同溶剂中溶解性能的研究, 探讨了共聚物与甲醇的络合机理以及自组装机理. 以格列奇特为模型药物, 研究了聚合物微球在不同环境下的振荡释放行为. 结果表明, 载药微球在30 min内对葡萄糖刺激迅速响应, 在葡萄糖浓度为3 g/L和无糖环境之间的振荡释放呈“开-关”式自调释放.     

高分子多孔微球产品的制备及其在类病毒颗粒分离纯化中的应用

高分子多孔微球在医药领域的分离纯化中应用广泛,是重要的化工产品。高分子多孔微球的形成是一个复杂的过程,利用聚合物与有机溶剂致孔剂的相分离,可得到小于100 nm孔径的多孔微球;而水和疏水性聚合物之间相分离程度远大于有机溶剂与聚合物间的相分离程度,因此可获得大于100 nm孔径的多孔微球。针对不同应用领域选择不同的方法,设计并制备出合理的微球结构,对多孔微球的实际应用十分关键。本综述介绍了纳孔、介孔、大孔微球产品的制备方法悬浮聚合和种子聚合法,重点介绍本课题组制备超大孔微球的方法--反胶团溶胀法和W/O/W复乳法,上述两种方法解决了常规方法难以制备大孔径微球产品的问题,拓展了多孔微球在类病毒颗粒等大尺寸蛋白分离纯化领域的应用。在此基础上,以HB-VLPs为模型对比了不同孔径微球对类病毒颗粒吸附量、回收率、结构、以及纯化效果的差异,揭示超大孔微球产品在类病毒颗粒分离纯化中的优势。     

聚合物微球调驱剂的制备及其在多孔介质中的微观渗流规律

采用反相微乳液法/乳液法制备了聚合物微球调驱剂，并在微流控芯片中进行了物模实验评价及模拟，分析了聚合物微球调驱剂在岩石孔隙中的输运机理。结果表明：多孔介质的孔隙大于聚合物微球调驱剂直径时，大量微球在微通道中的运移会增加流动阻力及近壁面区域的剪切力；多孔介质的孔隙略大于聚合物微球调驱剂直径时，多个聚合物微球一同进入；在随机生成的多孔介质结构中，微球大颗粒的通过能够导致更大的压力波动，但微球数量越多，滞留情况越严重。     

微盘电极应用-聚在乙二醇离子导体中的伏安分析

在聚乙二醇离子导体中, 研究了二茂铁在其中的伏安性质, 结果表明如果电活性物质与聚合物溶剂不发生相互反应, 那么电活性物质在聚合物溶剂中的扩散仍然遵循Fick扩散方程, 其伏安结果可以定量描述。提出了在聚合物离子导体中不需要知道电活性物质的摩尔浓度就可估算扩散系数的伏安方法, 探索了在聚合物离子导体中电活性物质的扩散规律。     

微盘电极应用-聚在乙二醇离子导体中的伏安分析

在聚乙二醇离子导体中, 研究了二茂铁在其中的伏安性质, 结果表明如果电活性物质与聚合物溶剂不发生相互反应, 那么电活性物质在聚合物溶剂中的扩散仍然遵循Fick扩散方程, 其伏安结果可以定量描述。提出了在聚合物离子导体中不需要知道电活性物质的摩尔浓度就可估算扩散系数的伏安方法, 探索了在聚合物离子导体中电活性物质的扩散规律。     

利用酸敏感超支化聚缩醛制备聚乳酸多孔微球

通过缩醛转移聚合合成了一种具有酸敏感特性的超支化聚缩醛(HBPAs),对该聚合物降解行为的研究表明,该聚合物具有很强的酸敏感特性,在pH为5.0时,短时间内可发生迅速的降解,而在pH为7.4时,该聚合物基本不发生降解.利用该聚合物的酸敏感特性,其在弱酸性条件下降解速率远远超过PLA的降解速率,制备了多孔PLA微球.进一步研究发现,通过调控超支化聚缩醛(HBPAs)与PLA的投料比,可以线性调控PLA多孔微球的孔径尺寸,并拟合得到了线性方程.DSC结果以及对微球降解过程的观察表明,在共混微球内部,HBPAs与PLA会发生一定的相分离,使得在酸降解的过程中,更有利于微球内部的HBPAs组分发生降解.     

微盘电极应用在乙二醇离子导体中的伏安分析

在聚乙二醇离子导体中,研究了二茂铁在其中的伏安性质,结果表明如果电活性物质与聚合物溶剂不发生相互反应,那么电活性物质在聚合物溶剂中的扩散仍然遵循Fick扩散方程,其伏安结果可以定量描述.提出了在聚合物离子导体中不需要知道电活性物质的摩尔浓度就可估算扩散系数的伏安方法,探索了在聚合物离子导体中电活性物质的扩散规律.     

Pollutants leaching behaviour from solidified wastes: a selection of adapted various models

Leaching tests are essential in the environmental assessment of stabilized wastes. Research programmes were conducted on their interpretation in order to develop tools for the evaluation of long term release of pollutants contained in solidified wastes. Models for the leaching of porous materials are discussed in this paper according to the specificity of the chemical species (i.e. transport model with total dissolution of species-diffusional model; transport model with progressive dissolution of species due to limitation of solubility-shrinking core model; and the model coupling transport and chemical phenomena). The leaching behaviour of pollutants (i.e. lead) solidified in a cement matrix was studied under different chemical conditions. Results have shown that the release of species whose solubilities depend on the physico-chemical conditions, and especially the pH (e.g. amphoteric metals), is governed by the solubility of the species in the pore water at local conditions and by the pH evolution within the matrix. A coupled dissolution/diffusion model was developed to describe the release of chemically complex species contained in a porous medium in contact with water. Leaching tests of cement matrices and artificial porous matrices containing calcium hydroxide and pollutants were conducted in order to validate the coupled dissolution/diffusion model. A good assessment of the retention of some pollutants contained in cement matrices could then be obtained by the association of two tests: solubilization of the pollutants related to the chemical context (pH) under steady state conditions and monolithic long term dynamic leaching tests in order to characterize the evolution of the chemical context (pH) and consequently the release of pollutants. The objective is to integrate this approach in the standardization process (CEN TC 292- WG 6, in progress).     

Numerical study of a drug release profile in the transdermal drug delivery system

Drug release by diffusion from an unstressed thin polymer film with a dissolved crystallizable component was simulated using a kinetic Monte Carlo model. This model was used previously to study Ostwald ripening in a high crystallizable component regime and was shown to correctly simulate solvation, diffusion, and precipitation. In this study, the same model with modifications was applied to the drug transportation and release in the low concentration regime of interest to the transdermal drug delivery system (TDS) community. We demonstrate the model's utility by simulating diffusion, crystal precipitation, growth and shrinkage during storage, and drug release from the thin TDS to a surface under different conditions. The simulation results provide a first approximation for the drug release profile occurring from TDS to skin. It has been reported that growth of drug crystals in TDS occurs mainly in the middle third of the polymer layer at relatively higher temperatures. The results from the simulations showed that the release rate and concentration profile of a TDS depend on the dissolution process of the crystal. At low storage temperature, the drug precipitates to form small evenly distributed crystals throughout the thickness of the TDS patch. The release rate of these small, evenly distributed crystals most closely matched that of a completely dissolved drug.     

Dynamic Release of Riboflavin from Ethyl Cellulose Coated Barium Alginate Beads for Gastrointestinal Drug Delivery: An in vitro Study

The present work describes the dynamic release of model drug riboflavin form uncoated and ethyl cellulose coated barium alginate beads in the media of continuous varying pH at the physiological temperature 37°C. The drug release behavior has been studied in the simulating gastric fluid (SGF, pH 1.2) for 0–2 h and then in the simulating intestinal fluid (SIF pH 6.8) for 2–48 h. In addition to the traditional dissolution test (TDT, the dynamic release has also been studied by a newly developed method, called ‘flow through diffusion cell’ (FTDC). The release profiles, obtained by using these two methods have been found to differ appreciably from each other. Moreover, the nature of the solid mass surrounding the beads in the FTDC method also influences the release behavior of beads. The uncoated beads demonstrated faster drug release of drug in the medium of lower pH (i.e., 1.2) as compared to that in the medium of pH 6.8 and the release process was found to be diffusion controlled.     

Morphological changes of ethylene/vinyl acetate-based controlled delivery systems during release of water-soluble solutes

Thin slabs of theophylline and monomer albumin release systems were prepared by dispersing 212-300 μm and 300-25 μm particles respectively, of these bioactive agents in a methylene chloride solution of ethylene/vinyl acetate (EVAc) copolymer (40 wt% vinyl acetate), and evaporating the solvent at low temperatures according to the Langer—Folkman technique. Compositions containing 21.41 wt%, 31.04 wt% and 40.0 wt% albumin, and 19.32 wt% theophylline were prepared. Solute release experiments were performed in deionized water at 37 ± 0.1°C under perfect-sink conditions. The concentration of released solute was determined by measuring the absorbance of the UV spectra at 276 nm for albumin and 272 nm for theophylline. Both solutes could be released for long periods of time at controlled rates. The main mechanism of release was established to be solute dissolution and diffusion through the generated, waterfilled pore structure. Photomicrographs present the main features of this pore network. Mercury porosimetry was used to determine the pore volume and size of pores for freezedried slabs before, during and after the dissolution/diffusion/release process. Considerable pore collapse was observed and pore diameters of 8-650 μm were detected. In addition to solution diffusion through large pores, diffusion might occur through small constrictions between large pores or through a pore network of much smaller pores created in the matrix.     

Image analysis studies of dimensional changes in swellable hydrophilic polymer matrices

Studies of the fronts which are created by the process of swelling, their movement and the effect of drug solubility on release mechanisms, are presented. Tablets comprising solely of hydroxypropyl methylcellulose (HPMC) (Metolose 90 SH 100 000 SR), HPMC with sodium diclofenac (relatively soluble in the buffer solution used) and HPMC with furosemide (insoluble in the buffer solution used) were prepared. The tablets were made by direct compression in a manual hydraulic press and the matrix swelling was studied by an optical analysis technique. During the experimental procedure measurements were taken of the gel layer dimensions, the movement of the swelling, and the erosion and diffusion fronts at different time points. These measurements allowed the investigation of the possible mechanisms involved in the swelling/release process. The results showed that the rate and mechanism of drug release from swellable matrices depends on the following factors: the dissolution, the diffusion of the drug, the translocation of undissolved drug particles in the gel layer, and the solubility of the drugs used. This is supported by the following: (a) the diffusion layer thickness, which is observed as a result of the presence of undissolved drug in the gel layer, increases in the case of the water insoluble drug furosemide and as a result the diffusion front converges on the erosion front; (b) from the analysis of the dissolution data it appears that sodium diclofenac is released as a result of diffusion via the gel layer as well as due to polymer relaxation and/or matrix erosion. Conversely, the release of furosemide is only dependent on the polymer relaxation and/or matrix erosion. Copyright © 2004 John Wiley & Sons, Ltd.     

Flow Through Diffusion Cell Method: A Better Approach to Study Drug Release Behavior as Compared to Traditional Dissolution Test Method

Co‐polymeric hydrogels consisting of N‐vinyl‐2‐pyrrolidone (NVP) and acrylic acid (AAc) were synthesized and evaluated for release of a model drug, i.e., vitamin B₁₂. Release studies in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 7.4), at 37°C, showed the hydrogels to be pH sensitive. An in vitro release study by ‘traditional dissolution test’ (TDT) showed that percent drug released from the hydrogel was nearly 8.6±2.1 and 83.2±4.8 in the media of pH 1.2 and 6.8, respectively. However, in order to incorporate in vivo GI conditions such as acidic pH and high water content in the stomach, low water content and the presence of a semi–solid mass in the large intestine, a new test model, called flow through diffusion cell (FTDC) was also used. The two approaches yielded almost different release profiles. The gels were characterized by thermogravimetric analysis and FTIR spectroscopy.     

Disentanglement and reptation during dissolution of rubbery polymers

The dissolution mechanism of rubbery polymers was analyzed by dividing the penetrant concentration field into three regimes that delineate three distinctly different transport processes. The solvent penetration into the rubbery polymer was assumed to be Fickian. The mode of mobility of the polymer chains was shown to undergo a change at a critical penetrant concentration expressed as a change in the diffusion coefficient of the polymer. It was assumed that beyond the critical penetrant concentration, reptation was the dominant mode of diffusion. Molecular arguments were invoked to derive expressions for the radius of gyration, the plateau modulus, and the reptation time, thus leading to an expression for the reptation diffusivity. The disentanglement rate was defined as the ratio between the radius of gyration of the polymer and the reptation time. Transport in the second penetrant concentration regime was modeled to occur in a diffusion boundary layer adjacent to the polymer-solvent interface, where a Smoluchowski type diffusion equation was obtained. The model equations were numerically solved using a fully implicit finite difference technique. The results of the simulation were analyzed to ascertain the effect of the polymer molecular weight and its diffusivity on the dissolution process. The results show that the dissolution can be either disentanglement or diffusion controlled depending on the polymer molecular weight and the thickness of the diffusion boundary layer. © 1996 John Wiley & Sons, Inc.     

The Long-term Release of Antibiotics From Monolithic Nonporous Polymer Implants for Use as Tympanostomy Tubes

A technology is elaborated for the fabrication of a novel tympanostomy tube (TT) from solidified polymer melts (Elvax and Polyurethane) and antibiotics (Ciprofloxacin and Usnic acid) for insertion into tympanic membrane (ear drum) according to the established surgical procedure. The long-term in vitro release kinetics of the antibiotics into liquid water has been assessed using standard methods. The measured kinetic curves revealed two stages of antibiotic release into the finite space. During the first stage (fast), the fast release rate is almost invariant and is determined by the diffusion through the steady diffusion layer formed due to solution agitation. In this first stage, the influence of the initial internal transport is weak because it takes place at negligibly small distance from interface and accordingly, at negligibly concentration drop. After the antibiotic concentration decreases within the much broader layer of matrix near interface, the internal transport becomes important. This manifests itself as the second stage in measured kinetics of release curves which is characterized by a gradual decrease in rate. The minimum inhibition concentrations of three antibiotics/antimicrobial compounds for four bacterial species were measured. The first stage of fast release from the polymer implant lasts 6 days at a polymer loading by Ciprofloxacin (0.03 g/cm(3)) and this was sufficient for preventing biofilm formation on the surface of the implant material. The measured kinetic curves of drug release showed more rapid decrease in the release rate compared to the Higuchi approximation. Comparison with existing theories, which account for the finite rate of drug dissolution, showed that this may explain the observed deviation from the diffusion-controlled Higuchi model. Large dimensions of drug particles and their aggregation retard the dissolution stage and consequently the release rate. Melt blending was found to cause the drug particle aggregation within polymer matrixes which was confirmed by microscopic reexamination of the polymer implant materials.     

Development and validation of a mechanistic model for the release of embelin from a polycaprolactone matrix

Embelin is a natural agent with antimicrobial, antifungal and analgesic activities. This work presents a mechanistic model for the release of embelin from a polycaprolactone matrix. Based on the results of embelin release experiments and Raman microscopy measurements, the model assumes a dual dispersion of the embelin: agglomerated and dispersed. Embelin release mechanism combines the effects of the liquid migration into the matrix, the drug diffusion, and the drug dissolution within the wetted matrix. The model is formulated in terms of four partial differential equations that account for the mass balances of dispersed, agglomerated, and dissolved embelin, and aqueous solution. Model predictions show that the release mechanism involves three stages: a burst stage, in which dispersed embelin is rapidly released; a transition stage, in which dispersed and agglomerated embelin are simultaneously released; and, once the dispersed embelin depletion, a stable release stage until the agglomerated embelin exhausts.