聚天冬氨酸水凝胶合成及其应用于药物控释的研究进展

聚天冬氨酸是一种新型的聚合氨基酸材料,具有很好的生物相容性、生物降解性。本文综述了聚天冬氨酸及其衍生物水凝胶的研究现状,介绍了化学交联、光交联、γ射线交联3种交联方法合成的聚天冬氨酸及其衍生物水凝胶,以及近年来聚天冬氨酸基凝胶对大分子蛋白药物、小分子抗炎性药物、抗癌和基因药物控释的研究进展,并对该凝胶在药物控释领域的发展方向进行了预测。     

智能型高分子水凝胶在药物控释中的应用研究进展

智能型高分子水凝胶因为能感应到外界环境因素的变化,并且发出响应—凝胶的体积或其他性质发生显著变化,从而导致药物可在定点位置,定时、定量的释放,所以近年来受到普遍重视.本文综述了近年来智能型高分子水凝胶中温度敏感型、pH敏感型以及葡萄糖、电场、磁场、光、微波等敏感型水凝胶及其在药物控释中的应用,介绍了其控释作用机理及应用...     

农药控释水凝胶的研究进展

水凝胶具有独特三维网络结构,可以容纳大量的水和流体物质,所以被广泛应用于农药控释领域.与合成材料相比,天然高分子材料具有可生物降解、环境友好、经济易得等优点,因此大量被用于水凝胶制备.综述了目前几种常见的天然农药控释水凝胶的研究进展,同时对农药控释水凝胶的发展前景进行了展望.     

快速响应智能水凝胶的研究进展

能响应外界刺激的智能水凝胶由于其特有的响应性,具有广泛的应用前景。做为药物控制释放载体的智能水凝胶,通常由于差的机械性能和慢的响应速度限制了它的实际应用。近年来,许多研究工作者围绕提高智能水凝胶的响应速度作出了大量的工作。综述了近年来提高智能水凝胶响应速度的研究进展。     

智能水凝胶应用研究进展

智能水凝胶是指在外界环境（如温度、pH、电场、溶剂性质、光强度和光波长、压力、离子强度等）发生变化时,性质随之发生相应变化的水凝胶,即具有环境响应性。作者详细介绍了智能水凝胶在药物控制释放、组织工程、物质分离、酶的固载及调光材料5个方面的应用研究情况。并对智能水凝胶未来的研究方向及应用前景进行了展望。     

智能水凝胶在生物载药领域的研究进展

智能水凝胶是一类具有三维网络结构、膨胀性好、吸水性强、易保水、超仿生等特点的新型功能高分子材料。由于其合成过程中加入了具有特殊结构、基团的单体或者大分子原料,如聚丙烯酰胺(PNIPA)类大分子、酸/碱基团(如羧基和氨基)、丙烯酸、聚氨类、偶氮苯(As)、聚电解质(高分子链上有可以离子化的基团)等,因此智能水凝胶是能够根据环境的温度、酸度、电场、磁场等变化做出有规律的结构和体积调整,或者导致凝胶组成发生变化的新型智能生物化学水凝胶材料,具有较高的智能性和响应性。本文根据水凝胶对外界环境的刺激不同表现出不同的响应情况,将凝胶分为:温度敏感性水凝胶、pH敏感性水凝胶、光敏感性水凝胶、压力敏感性水凝胶、电场敏感性水凝胶等。近年来,随着人们对医用水凝胶和药物缓释研究的深入,具有环境敏感性和较好生物相容性的智能水凝胶成为临床上药物控释材料的首选。     

纤维素/海藻酸钠基双膜水凝胶的制备及其药物控释研究

用阳离子纤维素(CC)和阴离子海藻酸钠(SA)制备出具有双膜结构的生物相容性水凝胶,探究了水凝胶在不同pH值环境下的药物控制释放行为。结果表明,在pH为7.4,进行单膜水凝胶释放牛血清白蛋白时,纯海藻酸钠水凝胶SA、SA/CC-1水凝胶、SA/CC-2水凝胶的药物释放时间分别为3,6,8 d,累积释放量分别为86%,84%,83%,即纤维素阳离子化程度更高的水凝胶释放药物更缓慢;在pH为2.0的条件下,单膜水凝胶释放牛血清白蛋白的累积释放量的最大值仅为6%,水凝胶的药物释放行为表现出pH敏感性。此外,在pH为7.4条件下,复合药物从双膜水凝胶中有序释放出来,外膜中的茶碱在药物释放的第3 d达到释放平衡,累积释放量为87%;内膜中的牛血清白蛋白在第4 d开始释放,在第11 d达到平衡,累积释放量为84%。该水凝胶有明显的药物控释作用,在生物医学领域有很大的应用前景。     

纤维素/海藻酸钠基双膜水凝胶的制备及其药物控释研究

用阳离子纤维素(CC)和阴离子海藻酸钠(SA)制备出具有双膜结构的生物相容性水凝胶,探究了水凝胶在不同pH值环境下的药物控制释放行为。结果表明,在pH为7.4,进行单膜水凝胶释放牛血清白蛋白时,纯海藻酸钠水凝胶SA、SA/CC-1水凝胶、SA/CC-2水凝胶的药物释放时间分别为3,6,8 d,累积释放量分别为86%,84%,83%,即纤维素阳离子化程度更高的水凝胶释放药物更缓慢;在pH为2.0的条件下,单膜水凝胶释放牛血清白蛋白的累积释放量的最大值仅为6%,水凝胶的药物释放行为表现出pH敏感性。此外,在pH为7.4条件下,复合药物从双膜水凝胶中有序释放出来,外膜中的茶碱在药物释放的第3 d达到释放平衡,累积释放量为87%;内膜中的牛血清白蛋白在第4 d开始释放,在第11 d达到平衡,累积释放量为84%。该水凝胶有明显的药物控释作用,在生物医学领域有很大的应用前景。     

智能水凝胶的研究进展

智能水凝胶是指在外界环境(如温度、pH值、电场等)发生变化时,性质随之发生相应改变的水凝胶,即具有环境响应性。水凝胶尤其是智能水凝胶由于其迷人的性质及潜在的应用引起广大科技工作者的研究兴趣。根据智能水凝胶对环境的响应情况,作者详细介绍了pH敏感性水凝胶、温度敏感性水凝胶、光敏感性水凝胶、电场敏感性水凝胶、磁敏感性水凝胶、盐敏感性水凝胶、化学物质敏感性水凝胶以及多重敏感性水凝胶的研究情况,同时对智能水凝胶的研究方向和应用前景进行了展望。     

智能型水凝胶材料及其应用

本文综述了智能型水凝胶的制备方法及该凝胶对环境的刺激响应性,重点介绍了它的温敏效应、pH敏效应、压敏效应、光敏效应及电敏效应。最后介绍了它的应用现状。     

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(l-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and the release data suggested that both the pH and PNH content played important roles in the drug release behaviors of the hydrogels.     

新型不饱和聚酯基亲水性药物缓释材料的制备

采用本体熔融聚合方法,以三羟甲基丙烷二烯丙基醚（TMPDE）对不饱和聚酯酰胺脲树脂进行封端,得到了一种药物缓释载体的亲水性预聚物,以盐酸环丙沙星为模型药物,制备了盐酸环丙沙星-不饱和聚酯酰胺脲树脂药片。研究了尿素含量和饱和二元酸对材料降解性能和亲水性的影响。体外降解和药物释放（37℃,pH 7.4 PBS缓冲溶液）结果表明,该空白材料的降解速率可通过改变尿素含量来调节;缓释药片释药平稳,持续释药时间可达30 d。     

Controlled drug release via minimization of burst release in pH-response kappa-carrageenan/polyvinyl alcohol hydrogels

Kappa-carrageenan/polyvinyl alcohol cross-linked hydrogels was formulated using genipin as a natural and non-toxic cross-linker to achieve a controlled drug release. β-Carotene was immobilized and the release study was evaluated under in vitro conditions. Monitoring β-carotene release was carried out by structure modification using cross-linker and minimization of burst release. It was found that using genipin can stop burst release in the hydrogels and control active material better than native films as a result of structural modification. This suggests that the burst release is depended highly on the degree of cross-linking and the mesh space available for drug diffusion. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are carried out to study the characteristics changes of native and cross-linked hydrogels. Also, field emission scanning electron microscope (FESEM) was performed to study microstructure of hydrogels. The transport mechanism seems to be determined by the strength of the gel network due to genipin concentration changes. Finally, diffusion coefficient is determined for native and cross-linked hydrogel.     

pH敏感型半纤维素水凝胶的制备及释药性能研究

利用自由基聚合方法制备了丙烯酸和丙烯酰胺共聚接枝半纤维素水凝胶,研究了水凝胶在不同pH(1.5、7.4、10)缓冲液中的溶胀动力学,并以阿司匹林作为模型药物,研究了其在模拟胃肠液(pH=1.5、7.4)中的释放性能。结果显示,制备的半纤维素水凝胶对阿司匹林具有明显的缓释效果,有望实现药物的控制释放。     

Diffusion and controlled release characteristics of pH-sensitive poly(2-(dimethyl amino)ethyl methacrylate-co-2-hydroxyethylacrylate) hydrogels

The authors describe a facial development of pH-responsive hydrogels composed of 2-(dimethylamino)ethylmethacrylate and 2-hydroxyethylacrylate via free-radical polymerization at 29°C. The hydrogels were characterized by FTIR, SEM, and XRD studies. The diffusional exponent (n), hydrogel network parameters such as average molecular weight between crosslinks (M_c), and polymer-solvent interaction (χ) were calculated by using swelling data. The hydrogels were encapsulated with 5-fluorouracil, the in vitro release data indicated that the maximum drug release was significantly achieved in pH 1.2 rather than in pH 7.4 and it was enhanced up to 30 h. These results suggested that the gels are highly useful for anticancer drug delivery applications.     

Chitosan tablets for controlled release of theophylline: Effect of polymer—drug wet or dry blending and anionic—cationic interpolymer complex

Chitosan tablets containing theophylline were prepared by directly compressing the wet or dry blended polymer—drug powders. The effects of the viscosity and swelling ability on the release rates of drugs were examined. The theophylline releasing rates of tablets prepared by polymer—drug wet blending increase with a decrease in the viscosity of the blending chitosan solution. On the other hand, the swelling ability of the polymer greatly influences the release kinetics of the tablets prepared by polymer—drug dry blending. Tablets prepared by both polymer—drug wet and dry blending were acid-nonresisted. Tablets in simulated gastric fluid disintegrated quickly, and the drugs were released within four hours. To retard the disintegrated rate of chitosan tablets in acid medium, interpolymer complex of chitosan with anionic polyelectrolyte (alginate) is needed. By this treatment, the swelling and erosion rate of the chitosan tablets could be reduced, then controlling the release rate of the theophylline can be achieved. Drug release mechanism of the various tablets were investigated by the model of Peppas; in addition, a nuclear magnetic resonance imagine microscopy is also introduced to examine the swelling or diffusion mechanism of various tablets. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 2495–2505, 1997     

Properties of hydrogels of atactic poly(vinyl alcohol)/NaCl/H2O system and their application to drug release

In order to prepare cost‐effective physically cross‐linked hydrogels including food salt sodium chloride, samples, were prepared with various concentrations of NaCl and respective atactic poly(vinyl alcohol) (a‐PVA), and were evaluated. It had been observed that hydrogels containing NaCl concentration (9–11 wt%) along with a‐PVA concentration 9–5% respectively exhibited higher melting points (91.5–95.1 °C). A higher melting point characterizes the hydrogel composition of a system like a‐PVA(7%)/NaCl(11%)/H₂O. The swelling degree of this hydrogel was found to be comparatively better at 37 °C than at any other temperature studied here. However, irregular Fickian swelling was found at this temperature. The UV light absorption maximum at 362–364 nm and minimum at 351 nm for this hydrogel had been found as evidence of physical cross‐linking. A drug, theophylline was loaded by solvent‐sorption and feed‐mixture dissolving methods. The feed‐mixture dissolving method is better than solvent sorption because of high drug loading, comparatively low fraction release rate and more sustained‐release of drug than that of solvent‐sorption. Theophylline was released twice as fast from the hydrogel after solvent‐sorption drug loading (3 h) than from that which used the feed‐mixture dissolving method (6.5 h). Theophylline‐loaded hydrogels of this system (feed‐mixture dissolving) were then prepared at high temperature (60 °C) thawing for 6 h followed by chilling at 0.4 °C for 3 h as one cycle. And the drug release behaviour and mass transfer were found almost the same as for chilling (24 h at 0.4 °C)–thawing (48 h at room temperature). Drug release behaviour was studied as apparently irregular Fickian diffusion (Higuchi Matrix Dissolution Model). © 2002 Society of Chemical Industry     

Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix^® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise^®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix^® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.     

Effect of hydrophobicity of a drug on its release from hydrogels with different topological structures

The effect of the topological structure; that is, the network heterogeneity, of hydrophobically modified, slightly acidic hydrogels on the binding and release of low molar mass drugs has been studied using ibuprofen and ephedrine as model compounds with varying water solubility. The difference in the heterogeneity of the gels has been produced by the choice of the hydrophobe copolymerized into the polymer network. The effect of the drug loading on the release kinetics has been investigated as well. The release of hydrophobic ibuprofen was slower from a strongly aggregated heterogeneous gel than from a more homogeneous one, because of the strong hydrophobic interaction between ibuprofen and the heterogeneous hydrogel. The release of hydrophilic ephedrine from the homogeneous gel with an initial drug content of 30 wt % of dry polymer showed negative time dependence, indicating that during and after the swelling of the gel, ephedrine started to bind to the polymer. However, the release of ephedrine from a heterogeneous hydrogel increased with time. This shows that the heterogeneous, aggregated polymer binds the hydrophobic substance more strongly than the homogeneous one does, and that the homogeneous network has higher affinity for the basic hydrophilic substance than the heterogeneous one does. The loading contents of ibuprofen and ephedrine affect the release rates in different ways because of the different binding and release mechanisms. The number of binding sites accessible for ephedrine inside the polymer network is assumed to change upon the swelling of the gel. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1031–1039, 1999