智能响应型水凝胶药物控释体系及其应用

药物控释体系可改善药物分子在机体内的释放、吸收、代谢和排泄过程,显著提高药物利用率并减弱药物的毒副作用。智能响应型水凝胶凭借其刺激响应性、亲水性和无毒性在药物控释方面得到了广泛的关注。本文介绍了智能响应型水凝胶药物控释体系的概念、机理和应用,详细归纳了智能响应型水凝胶药物控释体系的研究进展。按照刺激源不同将智能响应型水凝胶药物控释体系分为pH响应型、温度响应型、光响应型、生物分子(如葡萄糖、酶)响应型、外场(如电场、磁场)响应型、压力响应型、氧化还原响应型及多重响应型水凝胶药物控释体系。进一步介绍了智能响应型水凝胶药物控释体系在治疗癌症、急性肾损伤、眼病、糖尿病等疾病及抗菌、防止伤口感染等方面的应用。最后,基于目前智能响应型水凝胶药物控释体系存在的一些问题(如生物相容性差、存在突释或滞释现象、不可降解等)对其发展做出了展望。     

智能水凝胶研究最新进展

综述了近几年国内外智能水凝胶研究现状,重点介绍了对pH、温度、光、电、磁和特定生物分子敏感的水凝胶的研究创新以及智能水凝胶在药物控释载体、组织工程支架、血红蛋白氧栽体、生物传感器、蛋白质检验等生物医学领域应用的最新进展.     

明胶-聚异丙基丙烯酰胺水凝胶的pH、温度敏感性

用明胶(Gel)和N 异丙基丙烯酰胺(NIPAM)为原料,制备了Gel/聚异丙基丙烯酰胺(PNIPAM)水凝胶;研究了不同含量的水凝胶的温度、pH敏感性。结果表明:温度对水凝胶pH敏感性的影响取决于水凝胶的组成。明胶含量高的水凝胶,其pH敏感性几乎不受温度的影响;当0.500.90时,pH值几乎不影响水凝胶的温敏性。     

温度和pH双敏性PVME/CMCS水凝胶辐射交联制备及其性能

以聚甲基乙烯基醚(PVME)和羧甲基壳聚糖(CMCS)为原料, 采用电子束辐照交联方法制备聚甲基乙烯基醚/羧甲基壳聚糖(PVME/CMCS)水凝胶, 研究了温度、pH值、CMCS含量等对PVME/CMCS水凝胶溶胀度的影响, 同时以5-氟尿嘧啶(5-Fu)作模型药物, 初步探讨了凝胶药物释放性能. 结果表明, 辐射剂量在20—40 kGy时, 凝胶分数随辐射剂量的增加而快速增加, 辐射40 kGy以后趋于平衡. 在相同辐射剂量下, 随着体系中CMCS含量的增加, 凝胶分数反而减少. 该水凝胶具有一定的温度和pH敏感性, 其低临界溶解温度(LCST)在35 ℃左右, 并且在相同时间内和25及37 ℃下的溶胀反复可逆, 表现出较快的响应性. pH<3.0和pH>5.0时, 溶胀度较大; pH值为3.0~5.0时, 凝胶网络由于静电力收缩, 溶胀度较小. CMCS含量的增加和辐射剂量的减小均可提高凝胶载药量. 药物释放时间可通过改变体系中CMCS的含量和辐射剂量来调节.     

智能水凝胶双抗癌药物控释体系

近年来,基于联合用药策略的双药物控释体系的研究为降低抗癌药物毒性和提高疗效提供了有效途径。水凝胶作为一类高临床应用价值的药物载体,在药物控释方面具有广泛的应用前景。癌症是危害人类健康和生命的疾病之一,当人体内正常细胞发生癌变后,癌变细胞周围会发生一些显著的变化。因此,根据肿瘤细胞与正常细胞在体内环境及体外环境的差异,发展了多种智能型水凝胶双抗癌药物控释载体。它能够在感知外界因素的刺激下发生内部结构的变化,从而实现对药物的可控释放。与此同时,随着新的治疗手段的兴起和更多抗癌作用靶点的发现,水凝胶载体也成功实现了化学药物和生物治疗因子的同时负载和可控释放。本文将从不同智能型水凝胶载体如何负载、控释双抗癌药物及水凝胶药物载体中药物的组合方式两方面综述智能型水凝胶双抗癌药物控释体系最新研究进展,并展望其发展前景。     

壳聚糖基智能水凝胶的研究进展

壳聚糖是一种天然高分子,含有氨基和羟基等特征基团;水凝胶是一种高分子交联网络体系,具有亲水性,在水中能够溶胀并保持大量水分而不溶解;“智能化”是自发地对外界环境刺激产生响应的一种特性.壳聚糖基智能水凝胶具有良好的生物相容性和可降解性,正倍受广大研究学者的关注.文章综述了近年来关于pH敏感型、温度敏感型以及pH/温度双重敏感型壳聚糖基智能水凝胶的研究概况,介绍了壳聚糖基水凝胶在医学领域如组织工程、药物释放方面的应用并对其未来的发展方向进行了探讨.     

温度及pH值敏感水凝胶的合成和应用

直接将丙烯酸单体与N-异丙基丙烯酸胺共聚交联合成了温度及pH值敏感的水凝胶。包埋于水凝胶中的药物的释放随温度升高和pH值增大而加快，药物的释放兼有温度和pH值敏感性，对pH值的响应更加显著。     

磁场敏感性水凝胶研究进展

磁场敏感性水凝胶是一类由聚合物三维网络和磁性组分所构成的复合凝胶,其在药物控制释放、人工肌肉、酶的固定与蛋白质分离等领域具有良好的应用前景。本文综述了磁场敏感性水凝胶的制备方法及其在上述领域的应用。     

CS-PMA30水凝胶对考马斯亮蓝控释性能的研究

壳聚糖(CS)是自然界中唯一的聚阳离子碱性多糖,具有良好的组织相容性、生物可降解性、无毒、无刺激、pH响应性等优点,因而在药物控释领域的具有潜在的应用价值。将聚阳离子壳聚糖与聚阴离子甲基丙烯酰氧乙基磷酰胆碱-甲基丙烯酸二元共聚物(poly(MPC-co-MA),PMA30)进行静电复合,制备CS-PMA30聚离子水凝胶。以考马斯亮蓝为模型药物,对CS-PMA30水凝胶的控释性能进行研究。结果表明,该CS-PMA30体系是通过静电作用形成的物理交联水凝胶,具有pH响应性,有望在药物控释、组织工程等领域得到广泛应用。     

pH/温度双重敏感性微凝胶的合成与应用

智能微凝胶是一类具有独特物理、化学性质的聚合物网络和溶剂组成的体系, 在众多的领域具有潜在的应用.本文介绍了近年来pH和温度双重敏感性微凝胶的研究概况、制备方法及其在药物控制释放、分离纯化和光子晶体方面的应用.     

温敏性抗菌水凝胶的制备与控释技术研究进展

温敏水凝胶是一类通过感知温度变化使自身发生相变的智能型聚合物凝胶,通过负载抗菌剂或抗菌性单体制备抗菌水凝胶是近年来药物控制释放、组织工程以及生物免疫等领域关注的热点。本文概述了负载抗菌剂型温敏性抗菌水凝胶的物理交联和化学交联制备技术的研究概况,着重阐述了温敏性抗菌水凝胶的孔径调控、制备材料调控、载药模式调控等技术的研究进展,并对温敏性抗菌水凝胶的控释技术应用前景,特别是在生物质材料领域的应用前景进行了展望。     

Effect of Sodium Alginate on the Properties of Thermosensitive Hydrogels

Sodium alginate (SA ) was combined with poly(N ‐isopropylacrylamide) (PNIPAAm ) to prepare thermosensitive hydrogels through semi‐interpenetrating polymer network (semi‐IPN ) and fully interpenetrating polymer network (full‐IPN ). The thermosensitive, swelling, mechanical, and thermal properties of pure PNIPAAm , SA /PNIPAAm semi‐IPN , and Ca‐alginate/PNIPAAm full‐IPN hydrogels were investigated. The formation of semi‐IPN and full‐IPN significantly improved the hydrogels’ swelling capability and mechanical properties without altering their thermosensitivity. 5‐Fluorouracil (5‐Fu) was selected as a model drug to study the release behaviors of the hydrogels. It was found that in vitro controlled drug release from semi‐IPN hydrogels showed an initial release burst, followed by a slower and sustained release, before reaching equilibrium. Full‐IPN hydrogels showed slow and sustained release during the whole process. Temperature and pH were found to affect the rate of drug release. Ca‐alginate/PNIPAAm full‐IPN hydrogels have potential application as drug delivery matrices in controlled drug release.     

Factors affecting prednisolone release from hydrogels prepared with water-soluble dietary fibers, xanthan and locust bean gums.

The release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums was investigated. Newly developed equipment was employed in order to increase the gum concentration in the hydrogels. The apparent release rate of prednisolone from the hydrogels decreased with increasing gum concentration, suggesting that the diffusion of drug molecules was mainly controlled by the density of the three-dimensional network structure in the matrix. The effect of additives such as glycerin and sucrose on the release behavior of prednisolone was also investigated in detail. Drug release was significantly lowered by the addition of these compounds to these hydrogels. A linear relation was observed between the apparent release rate of prednisolone and microscopic viscosity of the hydrogels. These results indicated that the drug release could be controlled not only by the density of the network structure but also by the microscopic viscosity of the hydrogels.     

Chitosan based hybrid hydrogels for drug delivery: Preparation,biodegradation, thermal,and mechanical properties

In the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5-fluorouracil. The fabricated hydrogels were characterized via FT-IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5-FU due to these properties.     

Ion Exchange Controlled Drug Release from Polymerized Ionic Liquids

In this work ion functionalized hydrogels as potent drug delivery systems are presented. The ion functionalization of the hydrogel enables the retention of ionic drug molecules and thus a reduction of burst release effects. Timolol maleate in combination with polymerized anionic 3‐sulfopropylmethacrylate potassium and ibuprofen combined with cationic poly‐[2‐(methacryloyloxy)ethyl] trimethylammonium chloride are investigated in respect to their drug release profile. The results are showing an ion exchange depending release behavior instead of a diffusion‐controlled drug release as it is known from common drug delivery systems. Furthermore, the suitability of such hydrogels for standard methods for sterilization is investigated.     

可注射水凝胶的制备与应用

可注射水凝胶在再生医学和药物控释等方面有着广泛的用途,是近年来生物医用材料领域新的研究方向.本文综述了近年来人们在可注射水凝胶制备和应用方面的研究进展,最后展望了其发展前景.     

Software control of intelligent drug releases using stimuli-responsive release systems and IR data communication

Intelligent drug delivery systems using UV polymerized hydrogels controlled by software were developed. The conditions of drug releases such as drug concentration, timing and amount of released drug could be controlled. It was also shown that the release threshold and the program design could be modified by IR data communication.     

Biodegradable and antibacterial poly(azomethine‐urethane)‐chitosan hydrogels for potential drug delivery application

In this study, biodegradable and antibacterial poly(azomethine‐urethane) (PAMU)‐ and chitosan (CS)‐based hydrogels have been prepared for controlled drug delivery applications. Structural and morphological characterizations of the hydrogels were performed via Fourier transform‐infrared and scanning electron microscopy analyses. Thermal stability, hydrophilicity, swelling, mechanical, biodegradation, protein absorption properties, and drug delivery application of PAMU‐ and CS‐based hydrogels were also investigated. The swelling performance of the hydrogels was studied in acidic, neutral, and alkaline media. Swelling results showed that the hydrogels have higher swelling capacity in acidic and alkaline media than neutral medium. Biodegradation experiments of the hydrogels were also studied via hydrolytic and enzymatic experiments. The drug release property of the hydrogel was carried out using 5‐fluoro uracil (5‐FU), and 5‐FU release capacity of the hydrogels was found in the range from 40.10% to 58.40% after 3 days.     

A controlled-release strategy for the generation of cross-linked hydrogel microstructures

Microscale hydrogels of controlled sizes and shapes are useful for cell-based screening, in vitro diagnostics, tissue engineering, and drug delivery. However, the rapid cross-linking of many chemically and pH cross-linkable hydrogel materials prevents the application of existing micromolding techniques. In this work we present a method for fabricating micromolded calcium alginate and chitosan structures through controlled release of the gelling agent from a hydrogel mold. Replica molding was employed to generate patterned membranes, whereas microtransfer molding was used to produce microparticles of controlled shapes. To explore the viability of this technique for producing complex tissue engineering micro-architectures, this approach was used to generate cell-laden size- and shape-controlled 3D microgels as well as composite hydrogels with well-defined spatially segregated regions. In addition, shape-controlled microstructures that can exhibit differential release properties were loaded with macromolecules to verify the potential of this approach for drug delivery applications.     

Orthogonal Enzymatic Reactions to Control Supramolecular Hydrogelations

Enzyme‐responsive hydrogels have great potential in applications of controlled drug release, tissue engineering, etc. In this study, we reported on a supramolecular hydrogel that showed responses to two enzymes, phosphatase which was used to form the hydrogels and esterase which could trigger gel‐sol phase transitions. The gelation process and visco‐elasticity property of the resulting gel, morphology of the nanostructures in hydrogel, and peptide conformation in the self‐assembled nanostructure were characterized by rheology, transmission electron microscope (TEM), and circular dichroism (CD), respectively. Potential application of the enzyme‐responsive hydrogel in drug release was also demonstrated in this study. Though only one potential application of drug release was proved in this study, the responsive hydrogel system in this study might have potentials for the applications in fields of cell culture, controlled‐drug release, etc.