聚氨基酸材料在药物控释系统中的应用

聚氨基酸材料是一类具有良好生物相容性的高分子材料,在控释药物领域有独特的用途,我们就氨基酸材料在控释药物中类型,侧链修饰性,剂型,结构及生物相容性等方面作一简要的综述。     

可生物降解聚合物作为药物载体的应用进展

目前作为控制释放体系的药物载体材料大多是高分子聚合物材料。生物降解聚合物在一定时间内能被水解或酶解成小分子,可通过生理途径代谢排出体外,不需二次手术取出载体材料,因此比生物惰性材料更安全、更可靠,有更好的生物相容性,成为了药物载体的首选材料。简要综述了主要常用生物降解性聚合物在药物控释体系中的应用进展。     

药物缓释涂层支架的材料学特点及其生物相容性

目的:阐述药物涂层支架的材料学特点,分析其生物相容性。方法:检索PubMed数据库和中国期刊全文数据库有关药物缓释涂层支架材料学特点及生物相容性的文献,以"心血管,药物缓释,雷帕霉素,紫杉醇,冠状动脉,生物相容性,支架材料"为检索词,对资料进行初审,并查看文献后的引文文献。排除重复研究或Meta分析类文章。结果:①心血管支架中药物涂层支架材料的改进更新均以改善生物相容性和生物力学性能为目标。②心血管支架的生物相容性是一个复杂的连锁过程,血液相容性和组织相容性是评定生物相容性的两项基本内容。③利用有限元分析心血管支架材料的力学特性可为未来支架的优化设计提供有益的帮助。结论:药物涂层支架的研究涉及药物学、生物学、材料学多学科交叉,研究药物缓释载体的控释机制,寻找血液相容性更好的药物缓释载体,加强缓释载体与机体的结合强度是当前支架药物缓释载体研究所要解决的问题。     

脂肪族聚酯类生物材料亲水性改性的研究进展

主要综述了丙交酯、乙交酯或ε-己内酯与亲水性的聚乙二醇、氨基酸、N-乙烯基吡咯烷酮和聚乙烯醇等亲水性物质进行嵌段或接枝共聚合反应,制备具有亲水性、温敏性或PH敏感性的共聚物.为缓控释药物、组织工程和体内植入器械提供组织相容性好、保持蛋白药物活性、无毒的生物医用材料.     

聚乳酸-聚乙二醇共聚物的生物学效应研究

目前报道最多用于药物控释系统的载体材料是聚乳酸（PLA）及其共聚物聚乳酸-聚乙醇酸（PL-GA）。它们虽然生物相容性好，降解产物可被人体代谢吸收，也是FDA批准可用于人体的生物降解材料，但存在疏水性太强，对亲水性药物的亲合力弱导致包裹效率低，药物的活性易遭到破坏等缺点。     

中国科学家成功制备新颖金纳米囊泡

<正>据Ha W[Nanotechnology,2013,24(49):495103-495103.]报道,中国科学院成都生物研究所李帮经副研究员长期致力于基于环糊精主客体识别的自组装生物医药材料研究,针对金纳米粒子杂化囊泡研究中存在的问题,利用环糊精修饰的金纳米粒子和客体分子修饰的聚合物,成功制备了一类新颖的、具有优异生物相容性的聚乙二醇(PEG)和聚异丙基丙烯酰胺(PNIPAM)同时修饰的纳米囊泡。探索自身具有示踪功能的智能药物控释材料,实现药物可控释放是目前药物载体研究的热点和难点。针对金纳米粒子的优越     

应用于3D生物打印的甲基丙烯酸酐化明胶水凝胶相关理化性能的研究进展

甲基丙烯酸酐化明胶（GelMA）水凝胶由明胶和甲基丙烯酸（MA）聚合反应合成。GelMA水凝胶的制备方法简单，并具有良好的生物相容性及机械性能可调节性，受到众多研究者的关注。其在伤口敷料、药物释放支架及组织工程等生物医学工程领域具有巨大的应用潜力。文章对GelMA水凝胶的制备及其性能进行概括，对近年来利用纳米材料、天然聚合物和合成聚合物与GelMA水凝胶结合对材料改性进行综述，并对应用于3D生物打印的多功能GelMA水凝胶未来发展方向进行总结与展望。GelMA水凝胶属于多肽类水凝胶，脆弱易碎裂的特征极大限制了其应用，经过后期的改性提高力学性能的同时，可能将造成其生物相容性的降低，使材料的最终临床转换面临重大挑战。未来将通过不断探索复合天然/合成聚合物的混合水凝胶，提升支架的机械性能，同时保留GelMA优越的生物相容性。特别是纳米材料与GelMA水凝胶结合，将支架实现智能功能，尤其是在敷料支架领域的研究。     

聚-(3-羟丙基)-DL-天冬酰胺组织相容性的初步观察

药物控释高分子材料要求有良好的生物相容性。我们对聚－（３－羟丙基）－ＤＬ－天冬酶胺（ＰＨＰＡ）材料进行了皮下埋植实验、组织病理学观察、血生化和微核等检测,早期,在埋植部位出现了异物反应,第１３天部分小鼠肝组织小血管边出现轻度炎症反应,３４ｄ上述反应逐渐减轻或消失,肝肾组织细胞形态和功能基本正常,实验表明,ＰＨＰＡ具有良好的生物相容性。     

壳聚糖及衍生物在药物制剂中的应用

目的：总结近年壳聚糖及衍生物在药物制剂中的应用现状。 方法：由作者应用计算机检索维普数据库,检索时限1999-01/2010-10。检索关键词：壳聚糖,缓释,药物,应用。纳入有关壳聚糖的制备方法及其在药物制剂中应用的文章,排除较陈旧文献。共保留相关文献20篇进入结果分析。 结果：壳聚糖具有良好的生物相容性、可生物降解性、无毒性和易成膜性,在国内外药学领域,壳聚糖应用于缓释、控释制剂的研究颇受人们关注。利用壳聚糖特有的物理化学性质,如遇酸膨胀形成凝胶、有良好成膜性及促进多肽类、蛋白质药物的透黏膜吸收等特点,人们一般将壳聚糖以片剂、成膜材料及微球、微囊等形式,作为缓释、控释制剂的骨架材料。 结论：用壳聚糖所开发的缓控释制剂,均衡了释药速率,减少了药物对正常组织细胞的毒副作用。     

壳聚糖基聚电解质的生物医用前景

背景：利用壳聚糖阳离子聚合物特性,以不使用化学交联剂为前提在温和条件下制得的壳聚糖基聚电解质复合物,具有良好的生物相容性。 目的：综述近年来壳聚糖基聚电解质在药物载体、组织工程、伤口敷料、生物传感器、基因载体等方面的应用情况。 方法：由第一作者检索2004至2011年 ACS数据库和Elsevier Science电子期刊有关壳聚糖聚电解质在生物医用领域中的应用,尤其在药物载体、组织工程、伤口敷料、生物传感器及基因载体中的研究情况。 结果与结论：壳聚糖本身由于生物相容性好,可应用于生物体中作为良好的载体材料、支架材料、伤口敷料及生物传感器,经过与其他阴离子物质复合后可以保护壳聚糖本身良好性质,并且避免了使用化学交联剂所带来的生物毒性。壳聚糖的阳离子聚电解质本性使其能与黏液、阴离子表面和其他大分子如DNA产生强静电作用可有效应用于药物传送、基因治疗、固定生物酶等;壳聚糖聚电解质凝胶独特的性质如pH值、离子强度、电场敏感性,可使其通过对外界环境的改变作出不同响应,实现对生物组织的模拟、刺激响应药物控释,并且壳聚糖具备优异的抗菌性、止血性、亲水性和透气性,能够有效促进伤口愈合。     

药物控释载体材料的研究与应用

背景：作为控制释放体系的药物载体材料大多是高分子材料,但部分纳米无机材料也正逐步应用到药物控释材料体系中并取得了很好的研究成果。因此,药物控释用载体材料的设计与研究应用越来越受到重视。 目的：对国内外药物控释载体材料的应用及最新研究进展作一综述。 方法：应用计算机检索CNKI和Elsevier SD数据库中1999-01/2011-01关于药物控缓释材料的文章,在标题和摘要中以“高分子,介孔材料,无机硅,磷酸盐,控释”或“polymer,mesoporous materials,Inorganic silicon ,calcium phosphate,controlled release”为检索词进行检索。选择文章内容与药物控缓释有关者,同一领域文献则选择近期发表或发表在权威杂志文章。纳入25篇文献进行综述。 结果与结论：药物控缓释载体材料以用药量小、作用时间长、靶向作用好等特点被广泛关注,但是仍存在载药后药物失活,丧失生物活性等缺陷,目前随着复合药物载体材料和经皮给药装置研究的发展,控缓释材料在临床治疗中的应用必将更加广泛。     

应用生物可降解材料玉米醇溶蛋白制备胃肠道生物黏附控释片

背景：胃肠道生物黏附控释制剂能延长药物制剂在胃肠道的停留时间,提高药物的生物利用度。 目的：制备5-氟尿嘧啶胃肠道生物黏附控释片。 方法：利用生物可降解性玉米醇溶蛋白为骨架材料和黏附材料,氟尿嘧啶为模型药,制备氟尿嘧啶胃肠道黏附控释片。对片芯工艺进行正交设计,优化包衣液的选择,观察生物黏附缓释片的体外黏附力及体内外相关性。 结果与结论：5-氟尿嘧啶玉米醇溶蛋白生物黏附片体外释放10 h内均符合零级释放特征,片剂具有较好的体外黏附力,且在2~8 h 内体内血药浓度较为平稳,没有明显峰谷现象,体内外释放吸收具有良好的相关性。     

Magnetically Guided Release of Ciprofloxacin from Superparamagnetic Polymer Nanocomposites

Tailored with superparamagnetic properties the magnetic nanocomposites have been thoroughly investigated in recent past because of their potential applications in the fields of biomedicine and bioengineering such as protein detection, magnetic targeted drug carriers, bioseparation, magnetic resonance imaging contrast agents and hyperthermia. Magnetic drug targeting has come up as a safe and effective drug-delivery technology, i.e., with the least amount of magnetic particles a maximum of drug may be easily administered and transported to the site of choice. In the present work novel magnetic drug-targeting carriers consisting of magnetic nanoparticles encapsulated within a smart polymer matrix with potential of controlled drug release is described. To make such magnetic polymeric drug-delivery systems, both the magnetic nanoparticles and antibiotic drug (ciprofloxacin) were incorporated into the hydrogel. The controlled release process and release profiles were investigated as a function of experimental protocols such as percent loading of drug, chemical composition of the nanocomposite, pH of release media and strength of magnetic field on the release profiles. The structure, morphology and compositions of magnetic hydrogel nanocomposites were characterized by FT-IR, TEM, XRD and VSM techniques. It was found that magnetic nanocomposites were biocompatible and superparamagnetic in nature and could be used as a smart drug carrier for controlled and targeted drug delivery.     

Fabrication and characterization of monodisperse PLGA–alginate core–shell microspheres with monodisperse size and homogeneous shells for controlled drug release

Monodisperse PLGA–alginate core–shell microspheres with controlled size and homogeneous shells were first fabricated using capillary microfluidic devices for the purpose of controlling drug release kinetics. Sizes of PLGA cores were readily controlled by the geometries of microfluidic devices and the fluid flow rates. PLGA microspheres with sizes ranging from 15 to 50 μm were fabricated to investigate the influence of the core size on the release kinetics. Rifampicin was loaded into both monodisperse PLGA microspheres and PLGA–alginate core–shell microspheres as a model drug for the release kinetics studies. The in vitro release of rifampicin showed that the PLGA core of all sizes exhibited sigmoid release patterns, although smaller PLGA cores had a higher release rate and a shorter lag phase. The shell could modulate the drug release kinetics as a buffer layer and a near-zero-order release pattern was observed when the drug release rate of the PLGA core was high enough. The biocompatibility of PLGA–alginate core–shell microspheres was assessed by MTT assay on L929 mouse fibroblasts cell line and no obvious cytotoxicity was found. This technique provides a convenient method to control the drug release kinetics of the PLGA microsphere by delicately controlling the microstructures. The obtained monodisperse PLGA–alginate core–shell microspheres with monodisperse size and homogeneous shells could be a promising device for controlled drug release.     

Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release

Macroporous chitosan scaffolds reinforced by beta-tricalcium phosphate (beta-TCP) and calcium phosphate invert glasses were fabricated using a thermally induced phase separation technique. These porous composite materials were specially designed as both a drug carrier for controlled drug release and a scaffold for bone regeneration. The controlled drug release of antibiotic gentamicin-sulfate (GS) loaded scaffolds and morphology of osteosarcoma MG63 cells cultured on the scaffolds were studied. In comparison with the GS loaded pure chitosan scaffolds, the initial burst release of GS was decreased through incorporating calcium phosphate crystals and glasses into the scaffolds, and the sustained release for more than 3 weeks was achieved. The possible mechanisms for the controlled drug release were investigated by SEM, FTIR, and measurements of the pH values of the PBS solution during the drug release test. SEM micrographs showed no apparent morphological differences for osteoblastic cells grown on the pure chitosan scaffolds and those grown on composite scaffolds. The cells were attached and migrated on these scaffolds, and exhibited a biological appearance, suggesting a good cellular compatibility.     

Controlled and extended drug release behavior of chitosan-based nanoparticle carrier

Controlled drug release is presently gaining significant attention. In this regard, we describe here the synthesis (based on the understanding of chemical structure), structural morphology, swelling behavior and drug release response of chitosan intercalated in an expandable layered aluminosilicate. In contrast to pure chitosan, for which there is a continuous increase in drug release with time, the chitosan–aluminosilicate nanocomposite carrier was characterized by controlled and extended release. Drug release from the nanocomposite particle carrier occurred by degradation of the carrier to its individual components or nanostructures with a different composition. In both the layered aluminosilicate-based mineral and chitosan–aluminosilicate nanocomposite carriers the positively charged chemotherapeutic drug strongly bound to the negatively charged aluminosilicate and release of the drug was slow. Furthermore, the pattern of drug release from the chitosan–aluminosilicate nanocomposite carrier was affected by pH and the chitosan/aluminosilicate ratio. The study points to the potential application of this hybrid nanocomposite carrier in biomedical applications, including tissue engineering and controlled drug delivery.     

利福平-异烟肼-控释型载药人工骨的实验研究

开发研究一种能承载多药并有控释特性的载药人工骨。利用三维打印技术,制备具有多层同心圆柱体结构的载药人工骨,并将利福平和异烟肼由内到外按特定顺序加载,观察微观结构、孔隙率、体外药物释放特性和体外细胞生物相容性。所制备的载药人工骨呈多孔结构,孔隙率(61.76±2.53)%、微孔孔径50~100μm,体外药物呈现序贯释放,双药释放峰值依次交替出现,持续释放时间超过50 d,MTT检测示细胞毒性0级,电镜观察细胞生长分化良好,并有大量细胞黏附于载药人工骨表面;三维打印技术可以精确地制备具有复杂结构的载药人工骨,制备的多药控释型载药人工骨具有药物缓释和序贯控释的特性,同时具有良好的孔隙率和细胞相容性,为骨结核治疗提供一种新型有效的手段。     

Carbon nanotube nanoreservior for controlled release of anti-inflammatory dexamethasone

On demand release of anti-inflammatory drug or neurotropic factors have great promise for maintaining a stable chronic neural interface. Here we report the development of an electrically controlled drug release system based on conducting polymer and carbon nanotubes. Drug delivery research using carbon nanotubes (CNTs) has taken advantage of the ability of CNTs to load large amounts of drug molecules on their outer surface. However, the utility of the inner cavity of CNTs, which can increase the drug loading capacity, has not yet been explored. In this paper, the use of multi-wall CNTs as nanoreserviors for drug loading and controlled release is demonstrated. The CNTs are pretreated with acid sonication to open their ends and make their outer and inner surfaces more hydrophilic. When dispersed and sonicated in a solution containing the anti-inflammatory drug dexamethasone, experiments show that the pretreated CNTs are filled with the drug solution. To prevent the unwanted release of the drug, the open ends of the drug-filled CNTs are then sealed with polypyrrole (PPy) films formed through electropolymerization. The prepared electrode coating significantly reduced the electrode impedance, which is desired for neural recording and stimulation. More importantly, the coating can effectively store drug molecules and release the bioactive drug in a controlled manner using electrical stimulation. The dexamethasone released from the PPy/CNT film was able to reduce lipopolysaccharide induced microglia activation to the same degree as the added dexamethasone.     

Drug entrapment in silica microspheres through a single step sol-gel process and in vitro release behavior

A single step sol-gel process was used to precipitate silica microspheres containing ibuprofen or naproxen for controlled drug delivery applications. The drug release behavior from these systems was analyzed in vitro. Pure ibuprofen and naproxen exhibited linear release with time, while sol-gel silica entrapped drugs were released with a logarithmic time dependence starting with an initial burst effect followed by a gradual decrease. Microscopic analysis combined with gravimety and infrared spectroscopy indicated that some of the drug is entrapped as large crystals attached to silica microspheres while the rest is encapsulated inside the microspheres. Drug-loaded silica microspheres with no open porosity and with a narrow particle size distribution were obtained. Both erosion of the microspheres and diffusion through them contributed to drug release. Sol-gel precipitation of silica microspheres is a promising method for drug entrapment and controlled release.     

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。