温敏凝胶原位植入给药系统：进展与挑战

采用温敏凝胶的原位给药系统是理想的长效给药系统。本文从凝胶材料和给药系统的制备、凝胶的机体反应和体内降解以及药物控释三方面,综述了该给药系统的研究进展,总结了关键技术和科学问题,分析了面临的挑战与解决途径。水凝胶网络的不规则形态和较低的机械轻度,其植入后引起的机体炎性反应、组织融合与水分快速流失及这些反应造成的凝胶网络结构和降解速率的个体差异性变化,是控制药物释放的主要困难。通过提高凝胶表面亲水性,降低其表面正电荷,或在其表面修饰抗炎性多肽,可减轻炎性作用、减缓组织融合;通过与亲水性高分子形成共混凝胶或互穿凝胶网络,以及共价交联等方式,可提高凝胶强度,保持凝胶网络的空间结构和水分;通过在凝胶表面建立扩散屏障、加强药物和凝胶骨架的相互作用、构建微粒/原位凝胶复合释药系统等技术,可进一步改善药物释放特征。     

缓控释制剂给药系统的研究进展

就现存的缓控释制剂给药系统做了综合的概述和评价,总结了近年来有关的应用研究进展,同时对其发展趋势与应用前景做了展望.     

天麻素温敏型鼻用原位凝胶的制备研究

以天麻素为主药,泊洛沙姆P407和P188为凝胶材料制备凝胶,考察P407、P188的浓度及药物的加入对胶凝温度和体系黏度的影响,优化处方组成;采用无膜溶出法,扩散池法和透析袋法考察凝胶的体外释药行为。确定天麻素含量为10%,以P407 20%,P188 1. 5%或2%为优化的处方组成,平均凝胶温度分别为31. 5℃和33. 6℃。体外释放结果显示三种方法药物均释放完全,无膜溶出法显示药物的释放量与溶蚀量具有良好的相关性;透析袋法表明药物以扩散和溶蚀相结合的方式释药,且以扩散方式为主。天麻素原位凝胶制备工艺简单,药物释放具有缓释行为,适合鼻腔给药。     

纳米温敏凝胶的研究进展

查阅近几年有关纳米温敏凝胶的文献资料,对其新载体新剂型的研究进展进行了综述。主要概述了温度敏感型原位凝胶与纳米载体相结合的复合体系的相关研究并进行总结,对该复合体系的进一步开发研究具有一定参考价值。     

注射型原位成型药物传递系统的研究现状

注射型原位成型药物传递系统在近年来得到了广泛关注。注射型原位凝胶植入局部位置并使多聚物以半固体形式贮存药物,这种形式相比其它传统的给药方式具有很多优点。本文重点介绍了原位系统中原位沉淀凝胶的贮药机制,特性及其优缺点。     

干扰素鼻腔给药系统的研究进展

干扰素鼻腔给药系统是目前研究的热点。干扰素作为细胞因子被用来治疗 30多种疾病 ,其鼻腔内给药可预防和治疗呼吸道病毒感染 ,如病毒性感冒和病毒性肺炎等。鼻腔局部给药使干扰素通过和鼻粘膜上的相应受体结合而得到良好的吸收 ,具有吸收迅速、完全 ,能避免肝脏首过效应等优点 ,扩大了干扰素的应用范围 ,减少毒副作用的发生。     

葛根素新型给药系统的研究进展

以葛根素为研究对象,通过查阅近几年的葛根素相关文献,对其新载体新剂型的研究进展进行总结与概述。结果显示:将葛根素与新型给药系统结合,为中药有效成分葛根素的推广和应用提供了一个有利的平台,有助于加快葛根素新剂型的研究和应用进程。最后总结了葛根素在药物制剂现代研究中的应用,并展望了其发展前景。     

穿心莲内酯新型给药系统的研究进展

目标:以穿心莲内酯为研讨对象,为制备新型给药系统的进一步探索与开发提供重要参考依据。措施:经查阅近几年有关穿心莲内酯的研究文献,对它新载体新剂型的研究进度做进一步的概述、对比及总结。结果与讨论:通过把穿心莲内酯和新型给药系统进行联合,为中药有效成分穿心莲内酯的推行和运用提供了一个有利的平台,有利于穿心莲内酯新剂型的研究及其应用进程的成果提高。总结了穿心莲内酯在药物制剂现代研究中的应用,并瞻望了发展前景。     

碳纳米管在壳聚糖温敏凝胶中的应用研究进展

随着复合材料的功能化和智能化的发展,温度敏感性凝胶的研究也不断深入。碳纳米管具有良好的热传导、电磁、光学性能,而且具有较大的比表面积和吸附性能,将功能化碳纳米管与各种聚合物复合制备温敏凝胶,可以增强温敏凝胶的缓释性、温度敏感性、pH响应性等,同时温敏凝胶也可增加碳纳米管的生物相容性,本文综述了碳纳米管和温敏凝胶在生物医学领域中的相关研究进展。     

葡萄糖敏感性给药系统的研究进展

基于糖尿病病理特点而设计的葡萄糖敏感性给药系统能够根据体内血糖浓度的变化而自主调节药物释放,从而有效地控制体内血糖浓度,极具应用前景。目前,葡萄糖敏感性给药系统主要为载有葡萄糖氧化酶、刀豆蛋白A和苯硼酸体系三种。本文综述了近些年来葡萄糖敏感性给药系统的研究及应用,为后期开发基于糖尿病理特点的智能给药系统的实验研究提供一些参考。     

Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.     

甲基纤维素湿敏水凝胶中溶菌酶微球性质的体外评价

Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.     

温敏凝胶的合成和应用

综述了近几年来温敏水凝胶的研究进展，并对温敏凝胶的合成方法、应用研究和发展前景进行了探讨。     

Thermosensitive PCL‐PEG‐PCL hydrogels: Synthesis,characterization, and delivery of proteins

In this work, a biodegradable and injectable in situ gel‐forming controlled drug delivery system based on thermosensitive poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) (PCL‐PEG‐PCL) hydrogels was studied. A series of PCL‐PEG‐PCL triblock copolymers were synthesized and characterized by ¹H‐NMR and gel permeation chromatography (GPC). Thermosensitivity of the PCL‐PEG‐PCL triblock copolymers was tested using the tube inversion method. The in vitro release behaviors of two model proteins, including bovine serum albumin (BSA) and horseradish peroxidase (HRP), from PCL‐PEG‐PCL hydrogels were studied in detail. The in vivo gel formation and degradation of the PCL‐PEG‐PCL triblock copolymers were also investigated in this study. The results showed that aqueous solutions of the synthesized PCL‐PEG‐PCL copolymers can form in situ gel rapidly after injection under physiological conditions. The PCL‐PEG‐PCL hydrogels showed the ability to control the release of incorporated BSA and HRP. The released HRP was confirmed to conserve its biological activity by specific enzymatic activity assay. The in vivo gel formation and degradation studies indicated that PCL‐PEG‐PCL copolymers hydrogels can sustain at least 45 days by subcutaneous injection. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PCL‐PEG‐PCL copolymers hydrogels show promise as an in situ gel‐forming controlled drug delivery system for therapeutic proteins. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Studies on Glutaraldehyde Crosslinked Chitosan Hydrogel Properties for Drug Delivery Systems

Chitosan was crosslinked with different amount of glutaraldehyde to prepare appropriate hydrogels to be used as drug delivery system. The swelling behavior of freeze-dried hydrogels in aqueous media at different temperature and pHs has been examined. The swelling, porosity and biocompatibility behavior of samples were investigated to check effects of polymer/polymer and polymer/drug interactions on these system characteristics. Obtained experimental results illustrates that with increasing crosslinking agent from 0.068 to 0.30, swelling of the prepared samples degrees from 1200% to 600% and pore diameters change from 100 to 500 µm. To investigate systems biocompatibility in gastric conditions, effects of crosslinker concentration on the pepsin enzyme activity have been studied using variation of relative viscosity of the system. Presented results also show that with increasing crosslinker agent concentration activity of enzyme reduces considerably and so crosslinker molar ratio to amine functional groups of chitosan must be less than 0.2.     

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization,Ex-Vivo Imaging,and In Vivo Evaluation

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CD_C-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CD_C-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CD_C-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CD_C-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.     

微/纳米药物给药系统的研究进展

在过去的几十年中,探索高效的微/纳米给药系统一直是药剂学领域的研究热点。不同的微/纳米颗粒已被用于药物输送的研究,以期实现有效靶向给药,最大限度地减少副作用,从而提高治疗效果。本文主要综述了微/纳米药物输送给药系统及在药物制剂领域应用。     

体内植入型药物释放系统研究进展

体内植入型药物释放系统为一类经手术植入体内或皮下,或经穿刺导入皮下的控制释药制剂,适用于靶向给药或长期给药。本文根据系统植入形式和释药机制的不同,将植入型药物释放系统进行了分类,并对各种植入药物体系的特点和存在的问题作了评述。反向温敏型注射式原位凝胶植入系统是一类最具潜力的长期释药系统,可实现药物的长期、安全、有效释放,具有广泛的应用前景。     

氟脲嘧啶微粒-壳聚糖微敏性水凝胶复合释药系统的制备

The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate formulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate （GP） solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profilles of a hydrophilic drug, 5-fluorouracil （5-FU）. Morphological examination by scanning electron microphotography demonstrated that large ＂pores＂ occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug （85% in f＇LrSt 8h）. Poly-3-hydroxybutyrate （PHB）, a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content （75%, by mass）. The release could sustain for about 10 months. Tiffs study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.