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。     

药物从片状溶胀控制释放系统中释放的数学模型

本文对药物从可溶胀高分子材料中释放的机理进行了研究。建立了药物从可溶胀高分子材料中释放的数学模型。同时考虑溶剂渗透引起材料松驰膨胀，在模型中引入了刻画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。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，特别对材料松驰控制的过程进行了分析。     

药物从片状溶胀控制释放系统中释放的数学模型

本文对药物从可溶胀高分子材料中释放的机理进行了研究.建立了药物从可溶胀高分子材料中释放的数学模型.同时考虑溶剂渗透引起材料松驰膨胀,在模型中引入了刻画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.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,特别对材料松驰控制的过程进行了分析.     

药物从多孔骨架聚合物系统中恒速释放的机理

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。对药物从多孔骨架聚合物系统中non -Fickian扩散现象进行了研究 ,特别对药物溶出机制控制的恒速释药现象进行了解释。     

球型双层储库式恒速药物释放系统释放机理的研究

本文对由粒状核心与外涂层构成的储库式释放系统进行了研究，建立了药物从此双层系统中释放的数学模型，利用此模型研究了内层基质和外层膜的扩散系数对药物释放的影响，此外还研究了温度对此的影响。结果发现当内层扩散系数大于外层扩散系数时药物的释放为零级释放     

盐酸四环素/α-TCP骨水泥载药体系的体外释放研究

对盐酸四环素/磷酸钙骨水泥药物释放体系进行了体外释放研究。XRD分析结果表明，一定含量的盐酸四环素的存在不会影响α-TCP的水化。在体外释放实验中，各种药物含量的载药体系均表现出了良好的缓释性能，持续释放时间超过1200h；由于盐酸四环素同磷酸钙的吸附与结合，当药物在体系中的含量发生改变时，释放控制机理发生改变。当抗生素在固相中含量较大时，药物释放速率以扩散控制为主。药物释放量满足时间平方根关系；当药物含量较低时，在释放前期，药物释放速率仍然以扩散控制为主；释放后期、药物分子从磷酸钙表面的解脱溶出与扩散对药物释放形成混合控制。     

药物从玻璃状高分子材料中控制释放的机理研究

本文对药物从玻璃状高分子材料中扩散的机理进行了研究。将药物扩散方程和溶剂扩散方程结合起来。对药物采用Fick扩散定律得到扩散方程，考虑到溶剂的渗入引起材料粘弹性的改变，以及状态的改变对扩散的影响，将扩散方程与粘弹性模型结合起来构成扩散方程，最终得到一个能刻画药物从不同状态材料中扩散的模型。所得结果与实验结果相符。     

壳聚糖复合微胶囊的研制及在维生素D2可控释放中的应用

研究了以壳聚糖为核心壁材，以乙基纤维素为包衣材料的控制释放体系，以．维生素D2为模型药物，采用喷雾干燥方法对其进行有效包覆，并用乙基纤维进行了涂覆。对不同制备方法的微胶囊的形态及释放效果进行了测试。并探讨了制备过程中壳聚糖浓度，壳聚糖分子量，乙酸浓度，维生素D2负载量等因素对药物释放方式的影响。所制备的微胶囊不仅在肠液中具有显著的缓释效果。并且大大降低了维生素D2在胃中的释放，达到肠溶的目的。     

辉光放电等离子体沉积抗菌素控释膜的研究

研究了在聚氨酯、环丙沙星复合物基质上，通过射频辉光放电，沉积等离子体膜层，借以控制药物释放速率的方法，测定了膜的结构，并在体外对药物释放规律进行了讨论。     

药物从溶蚀性高聚物基质内释放的双动边界问题

采用修正积分法，得到了药物从溶蚀性高聚物基质内释放的双动边界问题的近似解析解，给出了扩散边界和药物释放分数的计算公式及其在不同初装浓度和溶蚀速度下的计算结果，给出了药物满足零级释放的近似条件。这对研究药物从高聚物基质内的释放问题以及控释制剂的设计具有重要的意义。     

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.     

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.     

Preparation of porous scaffolds by using freeze-extraction and freeze-gelation methods

Freeze-fixation and freeze-gelation methods are presented in this paper which can be used to prepare highly porous scaffolds without using the time and energy consuming freeze-drying process. The porous structure was generated during the freeze of a polymer solution, following which either the solvent was extracted by a non-solvent or the polymer was gelled under the freezing condition; thus, the porous structure would not be destructed during the subsequent drying stage. Compared with the freeze-drying method, the presented methods are time and energy-saving, with less residual solvent, and easier to be scaled up. Besides, the problem of formation of surface skin can be resolved and the limitation of using solvent with low boiling point can be lifted by the presented methods. With the freeze-extraction and freeze-gelation methods, porous PLLA, PLGA, chitosan and alginate scaffolds were successfully fabricated. In addition to the presentation of the morphologies of the fabricated scaffolds, preliminary data of cell culture on them are as well included in the present work.     

Repair of long intercalated rib defects in dogs using recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate

Long intercalated defects in canine ribs can be repaired successfully using porous beta-tricalcium phosphate (beta-TCP) cylinders, infused with a biodegradable polymer (poly D,L-lactic acid-polyethylene block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). We previously reported the successful regeneration of bony rib and periosteum defects using beta-TCP cylinders containing 400 microg of rhBMP-2. To reduce the amount of rhBMP-2 and decrease the time required for defect repair, we utilized a biodegradable polymer carrier, in combination with rhBMP-2 and the porous beta-TCP cylinders. An 8 cm long section of rib bone was removed and replaced with an implant comprised of the porous beta-TCP cylinders and the polymer containing 80 microg of rhBMP-2. Six weeks after surgical placement of the beta-TCP cylinder/polymer/BMP-2 implants, new rib bone with an anatomical configuration and mechanical strength similar to the original bone was regenerated at the defect site. The stiffness of the regenerated ribs at 3, 6, and 12 weeks after implantation of the composite implant was significantly higher than that of ribs regenerated by implantation of rhBMP-2/beta-TCP implants. Thus, addition of the synthetic polymer to the drug delivery system for BMP potentiated the bone-regenerating ability of the implant and enabled the formation of mechanically competent rib bone. This new method appears to be applicable to the repair of intercalated long bone defects often encountered in clinical practice.     

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.     

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.     

Fabrication and in vitro characterization of porous biodegradable composites based on phosphate glasses and oligolactide-containing polymer networks

Degradable porous composite materials for use as temporary bone replacement or tissue engineering scaffolds were produced using a methacrylate-modified oligolactide polymer network and phosphate invert glasses in the system P2O5-CaO-MgO-Na2O-(TiO2). Porous glasses with an open interconnective porosity were produced by a salt sintering process. Compressive strengths were significantly enhanced by polymer coating of the inner surface of the porous glasses or by fabrication of glass powder-reinforced porous polymer specimens. In vitro degradation in simulated body fluid showed a degradation pattern of the composites which could be modulated by the composition and resulting solubility of the incorporated glass phase. Cytocompatibility of the composites was investigated in a FDA/EtBr viability assay using an MC3T3-E1 osteoblast-like cell line and showed good biocompatibility of the materials in vitro.     

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.     

Bone growth in biomimetic apatite coated porous Polyactive 1000PEGT70PBT30 implants

We recently, developed a simple one-day one-step incubation method to obtain bone-like apatite coating on flexible and biodegradable Polyactive 1000PEGT70PBT30. The present study reports a preliminary biological evaluation on the coated polymer after implantation in rabbit femurs. The porous cylindrical implants were produced from a block fabricated by injection molding and salt leaching. This technique provided the block necessary mechanical integrity to make small cylinders (diameter 3.5 x 5 mm2) that were suitable for implantation in rabbits. The coating continuously covered the surface of the polymer, preserving the porous architecture of outer contour of the cylinders. Two defects with a diameter of 3.5 or 4 mm were drilled in the proximal and distal part of femur diaphysis. The implants were inserted as press-fit or undersized into the cortex as well as in the marrow cavity. The polymer swelled after implantation due to hydration, leading to a tight contact with the surrounding bone in both defects. The adherence of the coating on the polymer proved to be sufficient to endure a steam sterilization process as well as the 15% swelling of the polymer in vivo. The coated Polyactive 1000PEGT70PBT30 has a good osteoconductive property, as manifested by abundant bone growth into marrow cavity along the implant surface during 4-week implantation. A favorable bioactive effect of the coating with an intimate bone contact and extensive bone bonding with this polymer was qualitatively confirmed. Concerning the bone ingrowth into the porous implant in the defect of 4 mm diameter, only marginal bone formation was observed up to 8 weeks with a maximal penetration depth of about 1 mm. The pore interconnectivity is important not only for producing a coating inside the porous structure but also for bone ingrowth into this biodegradable material. This preliminary study provided promising evidence for a further study using a bigger animal model.