药物从多孔骨架聚合物系统中控制释放的动力学模型

以组分的连续性方程为基础，建立了药物从多孔骨架聚合物系统中释放的数学模型。在模型中引入相对渗透速度来刻画药物释放过程中不同机理的影响，并用摄动方法对方程进行了求解。对所得结果进行了分析，特别对药物溶出机制控制的恒速释药现象进行了解释。     

亲水聚合物凝胶系统中药物控制释放两类特殊情况的数学模型

对药物从亲水聚合物凝胶系统中释放的机理进行了研究，建立了药物释放的数学模型。同时考虑溶剂渗透引起材料松驰膨胀，在模型中引入了反映应力应变关系的弹性体方程，用摄动方法对方程进行了求解。同时利用溶胀界面数和扩散德伯拉数，对不同机理控制下的介质移动过程和药物释放过程，特别是材料松驰控制的药物释放过程进行了分析。     

用于药物释放系统载体内的智能聚合物

用于药物释放系统载体内的智能聚合物［英］／ＢｉｏｍｅｄｉｃａｌＭａｔｅｒｉａｌｓ．——１９９４，２美科技人员介绍，由智能聚合物制取的药物释放系统，可用于治疗多种疾病。据研究人员介绍，智能聚合物，尤其是系水性网络，对物理环境很敏感。智能型聚合物有特殊结...     

丙烯酰胺与葡萄糖烯丙基酰胺共聚水凝胶的合成与释药性能研究

用葡萄糖内酯与烯丙基胺反应制备了葡萄糖烯丙基酰胺单体 (AAG) ,然后与丙烯酰胺和亚甲基双丙烯酰胺共聚得到含糖结构的水凝胶。以阿司匹林为模型药物 ,制备水凝胶缓释骨架片。通过对Peppas经验式中n值的详细考察 ,研究阿司匹林在不同骨架片中的释放度。证实骨架片中药物的释放是随着糖基单体的含量增加而减少。     

用水凝胶作粘膜粘附剂和生物粘附剂材料

用生物粘附技术控制的药物释放的主要目的是在体内某一部位放置一个释放装置，使药物能在某一特定部位增加药物的吸收。生物粘附剂受聚合物释放装置的性质以及药物自身等生物环境协同作用的影响。释放部位的选择和装置的设计要根据药物的分子结构和药理学性质来考虑。本文将讨论几个以生物粘附剂释放为中心的研究命题。其次，简短的回顾一下生物粘附的各项技术。继之，讨论几个粘附机理。同时，对聚合物系统的主要机理，包括吸附和扩散作详细的介绍。     

一种新型可降解缓释微系统的优化设计

多腔体的微型可降解高分子聚合物药物缓释系统是一种新型给药技术,其载体结构是利用MEMS工艺的制备特点,结合药物释放的要求和高分子聚合物生物降解特性进行设计的.为了达到该系统在体内长期释药的性能,对释药载体的结构进行参数优化十分必要.文中建立了具有多腔体的微型可降解高分子聚合物给药载体的释药模型以及载体的结构优化模型,仿真及优化结果表明该模型可以用来指导基于可降解材料的结构优化设计.     

琥珀酸美托洛尔HPMC骨架片释放影响因素研究

以羟丙基甲基纤维素（HPMC）为骨架材料，乙基纤维素（EC）为阻滞剂，采用湿颗粒压片法制备琥珀酸美托洛尔亲水凝胶骨架片，考察HPMC用量、HPMC黏度、EC用量、制备方法、压片压力、释放介质及转速对琥珀酸美托洛尔（MS）骨架片体外释药的影响。结果表明，MS骨架片体外释药符合Higuchi方程，药物释放机制是骨架溶蚀和药物扩散的综合效应；HPMC用量与黏度、阻滞剂用量、制备方法、压片压力对释放速率均有显著性影响；释放介质的pH值及转速对释放速率无显著性影响。     

用水凝胶作粘膜粘附剂和生物粘附剂材料

用生物粘附技术控制的药物释放的主要目的是在体内某一部位放置一个释放装置，使药物能在某一特定部位增加药物的吸收。生物粘附剂受聚合物释放装置的性质以及药物自身等生物环境协同作用的影响。释放部位的选择和位置的设计要根据药物的分子结构和药理学性质来考虑。本文将讨论几个以生物粘附剂释放为中心的研究命题。其次，简短的回顾一下生物粘附的各项技术。继之，讨论几个粘附机理。同时，对聚合物系统的主要机理，包括吸附和扩     

丝素材料的药物吸附释放性能与调控研究

为了了解丝素材料对药物等的吸附释放性能 ,并探讨对丝素材料的吸附释放性能的调控 ,用不同离子型化合物作为药物模型 ,比较了分别用未修饰和经羧基进行酰胺化修饰后的丝素制作成的多孔丝素凝胶对不同离子型的化合物的吸附释放行为。结果表明 :经修饰后丝素蛋白质的等电点为 pH6 .0左右 ,而天然的为pH4.0左右。未修饰和经修饰的多孔丝素凝胶都随着溶液 pH的上升 ,对阳离子化合物的吸附量增加 ,释放速度减慢 ;对阴离子化合物吸附量减少 ,释放速度加快。但在相同 pH下与未修饰相比 ,经修饰的多孔丝素凝胶所吸附的阳离子化合物的释放速度加快 ,释放量也增加 ;所吸附的阴离子化合物的释放速度和释放量则明显降低。用羧基酰胺化修饰的方法 ,可在一定程度上改变丝素材料对离子型化合物的吸附释放行为     

抗生素—多孔玻璃陶瓷(A-PGC)药物释放系统(DDS)的研制

目的研制抗生素多孔玻璃陶瓷(A-PGC)药物释放系统(DDS)为骨髓炎治疗提供一种新方法.方法将两种多孔玻璃陶瓷(PGC)浸于抗生素(含庆大霉素和头孢唑林钠)溶液,真空吸附,制得A-PGC.同法制得抗生素多孔羟基磷灰石陶瓷(A-PHA)作对照.测定其体外、体内释放抗生素的药物浓度及持续时间.结果A-PGC体外释放有效浓度的庆大霉素达42天以上,而A-PHA为28天.三种陶瓷洗脱液中头孢唑林浓度均低于庆大霉素浓度.A-PGC在兔股骨中维持有效浓度庆大霉素达8周以上且有良好的骨传导作用.结论A-PGC可望成为治疗骨髓炎的一种新方法.     

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film’s surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer’s degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer’s weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.     

Dexamethasone-loaded scaffolds prepared by supercritical-assisted phase inversion

The aim of this study was to evaluate the possibility of preparing dexamethasone-loaded starch-based porous matrices in a one-step process. Supercritical phase inversion technique was used to prepare composite scaffolds of dexamethasone and a polymeric blend of starch and poly(l-lactic acid) (SPLA) for tissue engineering purposes. Dexamethasone is used in osteogenic media to direct the differentiation of stem cells towards the osteogenic lineage. Samples with different drug concentrations (5–15 wt.% polymer) were prepared at 200 bar and 55 °C. The presence of dexamethasone did not affect the porosity or interconnectivity of the polymeric matrices. Water uptake and degradation studies were also performed on SPLA scaffolds. We conclude that SPLA matrices prepared by supercritical phase inversion have a swelling degree of nearly 90% and the material presents a weight loss of ～25% after 21 days in solution. Furthermore, in vitro drug release studies were carried out and the results show that a sustained release of dexamethasone was achieved over 21 days. The fitting of the power law to the experimental data demonstrated that drug release is governed by an anomalous transport, i.e., both the drug diffusion and the swelling of the matrix influence the release of dexamethasone out of the scaffold. The kinetic constant was also determined. This study reports the feasibility of using supercritical fluid technology to process in one step a porous matrix loaded with a pharmaceutical agent for tissue engineering purposes.     

Dexamethasone-releasing biodegradable polymer scaffolds fabricated by a gas-foaming/salt-leaching method

Dexamethasone, a steroidal anti-inflammatory drug, was incorporated into porous biodegradable polymer scaffolds for sustained release. The slowly released dexamethasone from the degrading scaffolds was hypothesized to locally modulate the proliferation and differentiation of various cells. Dexamethasone containing porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds were fabricated by a gas-foaming/salt-leaching method. Dexamethasone was loaded within the polymer phase of the PLGA scaffold in a molecularly dissolved state. The loading efficiency of dexamethasone varied from 57% to 65% depending on the initial loading amount. Dexamethasone was slowly released out in a controlled manner for over 30 days without showing an initial burst release. Release amount and duration could be adjusted by controlling the initial loading amount within the scaffolds. Released dexamethasone from the scaffolds drastically suppressed the proliferations of lymphocytes and smooth muscle cells in vitro. This study suggests that dexamethasone-releasing PLGA scaffolds could be potentially used either as an anti-inflammatory porous prosthetic device or as a temporal biodegradable stent for reducing intimal hyperplasia in restenosis.     

Sustained release system for highly water-soluble radiosensitizer drug etanidazole: irradiation and degradation studies

Etanidazole (one nitro-imidazole hypoxic radiosensitizer) is formulated as polymer matrix type controlled release devices in this study. A novel double polymer drug carrier, unlike the double wall microparticles, is fabricated for the purpose of drug delivery, with the following objectives in mind: (1) to have a high encapsulation efficiency, (2) to achieve a pusatile release profile suitable for the radiation schedule of radiotherapy, (3) to elucidate the degradation profile of these microparticles. Irradiation of the microparticles were also studied to investigate effects on release and degradation. At a dosage of 50 Gy (total dosage during a radiotherapy treatment period) showed no apparent effects on the tri-phase release profile. It consists of an initial burst in the first 72 h, followed by a slow and steady drug release phase, and finally a faster degradation controlled phase corresponding to the degradation state of the different microparticles. At 25 kGy (sterilization dosage), the release profiles of the drug carrier were drastically modified. The faster erosion of the polymer with high dosage irradiation hastened the drug release and shortened the release time span, accompanied by decreases in the polymer molecular weight and glass transition temperatures, which was not apparent from SEM imaging. Degradation studies suggested a heterogeneous degradation process, with the outer layer and inner matrix degrading at different rates. The modifiable tri-phase release profile using microparticles of different polymer blends implies that the release properties of the drug carriers can be modified for different treatment regimes.     

In vivo release of testosterone from vinyl polymer composites prepared by radiation-induced polymerization

Polymer-testosterone composites with long periods of controlled slow release were made by radiation-induced polymerization in a supercooled state at low temperature using glass-forming monomers. The in vitro release of testosterone from various vinyl polymer composites was found to follow a matrix-controlled process (Q-t1/2). The rate of drug delivery was accelerated with increasing water content of polymers. In experiments in vivo, the composites were implanted subcutaneously in the back of castrated rats during the 30 day test period. The in vivo release rate of testosterone was a little smaller than in vitro. This difference between two releases also increased with the increase of hydrophilicity of polymer. The physiological response in rats was investigated by measuring the weight of ventral prostate and serum testosterone concentration with testosterone-containing composites. The weight of ventral prostate increased linearly with increasing rate of drug release and the serum testosterone concentration could be correlated with the release and with the weight increase of ventral prostate. It was found from microscopic observation that the used polymer carriers had relatively good biocompatibility to cause little foreign body reaction.     

Paclitaxel-eluting composite fibers: drug release and tensile mechanical properties

New core/shell fiber structures loaded with paclitaxel were developed and studied. These composite fibers are ideal for forming thin, delicate, biomedically important structures for various applications. Possible applications include fiber-based endovascular stents that mechanically support blood vessels while delivering drugs for preventing restenosis directly to the blood vesel wall, or drug delivery systems for treatment of cancer. The core/shell fiber structures were formed by "coating" dense core fibers with porous paclitaxel-containing poly(DL-lactic-co-glycolic acid) (PDLGA) structures. Shell preparation ("coating") was performed by freeze-drying water in oil emulsions. The present study focused on the effects of the emulsion's formulation (composition) and processing conditions on the paclitaxel release profile and on the fibers' tensile mechanical properties. In general, the porous PDLGA shell released approximately 40% of the paclitaxel, with most of the release occurring during the first 30 days. The main release mechanism during the tested period is diffusion, rather than polymer degradation. The release rate and quantity increased with increased drug content or decreased polymer content, whereas the organic:aqueous phase ratio had practically no effect on the release profile. These new composite fibers are strong and flexible enough to be used as basic elements for stents. We demonstrated that proper selection of processing conditions based on kinetic and thermodynamic considerations can yield polymer/drug systems with the desired drug release behavior and good mechanical properties.     

Interpolymer complexes of poly(acrylic acid) and chitosan: influence of the ionic hydrogel-forming medium

Non-covalent polyionic complexes were developed for localized antibiotic delivery in the stomach. Freeze-dried interpolymer complexes based on polyacrylic acid (PAA) and chitosan (CS) were prepared in a wide range of copolymer compositions by dissolving both polymers in acidic conditions. The influence of hydrogel-forming medium on the swelling and drug release was evaluated. The properties of these complexes were investigated by using scanning electron microscopy, dynamic swelling/eroding and release experiments in enzyme-free simulated gastric fluid (SGF). The electrostatic polymer/polymer interactions generate polyionic complexes with different porous structures. In a low pH environment, the separation of both polymer chains augmented as the amount of cationic and carboxilic groups increased within the network. However, the presence of higher amount of ions in the hydrogel-forming medium produced a network collapse, decreasing the maximum swelling ratio in SGF. PAA:CS:A (1:2.5:2)-1.75 M complexes released around 54% and 71% of the amoxicillin in 1 and 2 h, respectively, in acidic conditions. A faster drug release from this interpolymer complex was observed when the ionic strength of the hydrogel-forming medium increased. Complexes with a high amount of both polymer chains within the network, PAA:CS:A(2.5:5:2), showed a suitable amoxicillin release without being affected by an increased amount of ions in the hydrogel-forming medium. These freeze-dried interpolymer complexes could serve as potential candidates for amoxicillin delivery in an acidic enviroment.     

Porous silicon-poly(ε-caprolactone) film composites: evaluation of drug release and degradation behavior

This work focuses on an evaluation of novel composites of porous silicon (pSi) with the biocompatible polymer ε-polycaprolactone (PCL) for drug delivery and tissue engineering applications. The degradation behavior of the composites in terms of their morphology along with the effect of pSi on polymer degradation was monitored. PSi particles loaded with the drug camptothecin (CPT) were physically embedded into PCL films formed from electrospun PCL fiber sheets. PSi/PCL composites revealed a release profile of CPT (monitored via fluorescence spectroscopy) in accordance with the Higuchi release model, with significantly lower burst release percentage compared to pSi microparticles alone. Degradation studies of the composites, using gravimetric analysis, differential scanning calorimetry (DSC), and field emission scanning electron microscopy (FESEM), carried out in phosphate-buffered saline (PBS) under simulated physiological conditions, indicated a modest mass loss (15%) over 5 weeks due to pSi dissolution and minor polymer hydrolysis. DSC results showed that, relative to PCL-only controls, pSi suppressed crystallization of the polymer film during PBS exposure. This suppression affects the evolution of surface morphology during this exposure that, in turn, influences the degradation behavior of the polymer. The implications of the above properties of these composites as a possible therapeutic device are discussed.     

Preparation and characterization of TAM-loaded HPMC/PAN composite fibers for improving drug-release profiles

The present paper reports the preparation and characterization of composite hydroxypropyl methylcellulose/polyacrylonitrile (HPMC/PAN)-medicated fibers via a wet spinning technique. Tamoxifen (TAM) was selected as a model drug. Numerous analyses were conducted to characterize the mechanical, structure and morphology properties of the composite fibers. The drug content and in vitro dissolution behavior were also investigated. SEM images showed that the TAM-loaded HPMC/PAN composite fibers had a finger-like outer skin and a porous structure. FT-IR spectra demonstrated that there was a good compatibility between polymer and drug. Results from X-ray diffraction and DSC suggested that most of the incorporated TAM was evenly distributed in the fiber matrix in an amorphous state, except for a minority that aggregated on the surface of fibers. The drug content in the fibers was lower than that in the spinning solution and about 10% of TAM was lost during spinning process. In vitro dissolution results indicated that, compared to TAM-PAN fibers, HPMC/PAN composite systems had weaker initial burst release effects and more drug-loading. The combination of hydrophilic polymer HPMC with PAN could improve the performance of polymer matrix composite fibers in regulating the drug-release profiles.