丙烯酰胺与葡萄糖烯丙基酰胺共聚水凝胶的合成与释药性能研究

用葡萄糖内酯与烯丙基胺反应制备了葡萄糖烯丙基酰胺单体 (AAG) ,然后与丙烯酰胺和亚甲基双丙烯酰胺共聚得到含糖结构的水凝胶。以阿司匹林为模型药物 ,制备水凝胶缓释骨架片。通过对Peppas经验式中n值的详细考察 ,研究阿司匹林在不同骨架片中的释放度。证实骨架片中药物的释放是随着糖基单体的含量增加而减少。     

超声引发抗肿瘤药物定时定量释放

研究超声对于高分子聚合物Pluronic P-105载药缓释系统的影响作用.方法 配制不同浓度的P-105溶液,研究P-105溶胶-凝胶转化点及其影响因素.构建P-105载米托蒽醌水凝胶系统,将水凝胶暴露于不同频率与功率的超声波作用下,一定时间后,用PBS缓冲液冲洗水凝胶,根据缓冲液中米托蒽醌的紫外吸光值计算得出超声引发的药物的释放量.结果 P-105的溶胶-凝胶转化点受P-105的浓度及外界环境温度的影响.在浓度低于26%的区域或较低温度时没有凝胶形成,浓度高于26%或者温度接近人体正常体温(或高于体温)时即为凝胶.P-105载药系统中药物的释放量与超声波的频率与功率有关,释放量随着超声功率增加而增加,随频率增加而降低.结论 超声可以引发高分子聚合物Pluronic P-105载药系统的药物定时定量释放.     

聚乙烯醇/丙烯酰胺接枝共聚物水凝胶的制备及表征

背景：交联水凝胶主要是使大分子链形成网状结构,网固交联基质,这样所得的水凝胶力学性能和透明性相对较差。 目的：采用自由基聚合机制制备聚乙烯醇/丙烯酰胺接枝共聚物水凝胶。 方法：以聚乙烯醇分子作为主链,聚乙烯醇分子中羟基为接枝点,共价接入丙烯酰胺单体。考察反应温度、时间、单体用量和引发剂用量对产物接枝率的影响,通过红外光谱表征聚乙烯醇/丙烯酰胺接枝共聚物共聚物的化学结构。 结果与结论：接枝聚合反应最佳反应条件：引发剂浓度0.04 mol/L、丙烯酰胺/聚乙烯醇(侧羟基)摩尔比6∶1、在40 ℃条件下反应4 h。经过FTIR分析,确认丙烯酰胺与聚乙烯醇发生了聚合反应;经过平衡溶胀测试,分析了接枝聚合物与聚乙烯醇的溶胀率随温度的变化关系,进一步证实了接枝聚合反应的发生,验证了接枝聚乙烯醇/丙烯酰胺接枝共聚物具有明显的温敏性能。      

智能水凝胶在组织工程中的应用

背景：与传统水凝胶相比,智能水凝胶能够对外界刺激诸如温度、pH值、光、磁场等作出不同的应答表现,产生二级结构甚至化学结构的变化,自发组装形成有序的超分子结构,最终形成具有三维结构的凝胶。 目的：综述智能水凝胶的研究现状及其在组织工程的应用。 方法：应用计算机检索中国知网及PubMed 数据库从建库至2014年有关智能水凝胶在组织工程中应用的文献,检索关键词为“水凝胶,组织工程学,hydrogel,Tissue engineering”。 结果与结论：智能水凝胶中包括温度敏感性、pH敏感性、光敏感性、磁敏感性及温度/pH双重敏感性水凝胶,其对于外界环境变化能自动感知并能作出响应性的反应,在药物递送系统、药物释放,修复和改善缺损组织等领域表现出一系列传统材料所没有的突出性能,尤其是在组织工程方面表现出相当的优越性：低免疫原性,减少了炎症和排斥作用;具备生物可降解性;能真正在三维尺度上模拟细胞所处微环境,从而利于细胞黏附、生长、迁移及分化等。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

温敏型凝胶的缓释作用与临床应用

文题释义：温敏型凝胶：是一种特殊的水凝胶,能根据一定温度从流动的液体(溶胶相)转变为非流动的水凝胶(凝胶相)。因其特性,在生物医学和制药方面有广泛的应用,即药物输送、细胞培养、组织工程等。聚N-异丙基丙烯酰胺：由单体N-异丙基丙烯酰胺聚合而成,其大分子链上同时具有亲水性的酰氨基和疏水性的异丙基,使线型聚N-异丙基丙烯酰胺的水溶液及交联后的聚N-异丙基丙烯酰胺水凝胶呈现温度敏感特性。 背景：温敏型凝胶是近年来兴起的一种药物新剂型,因其具有缓释、控释、靶向给药等优势而成为近年来的研究热点。 目的：总结搜索文献中温敏型凝胶各种缓释机制,以及温敏型凝胶在临床上的应用疗效。 方法：在万方、中国知网、维普、PubMed、谷歌学术等数据库中,以“温敏型凝胶,缓释,给药途径”为中文检索词,以“thermosensitive gel,sustained release,administration route”为英文检索词检索温敏型凝胶缓释机制及临床应用方面的文章。结果与结论：①温敏型凝胶具有最低临界溶解温度,能随环境温度改变而发生一定程度的相变,比其他剂型有更多的优势,能使药物在人体内发挥很好的缓释作用,降低药物毒性,防止药物外渗,并提高药物的稳定性,还具有很好的临床应用前景;②温敏型凝胶有着注射、口腔、耳内、鼻腔、眼内、皮肤等多种给药方式,具有广泛的应用前景。但是各种凝胶材料都存在不同缺点,比如天然生物材料具有可塑性差、机械强度不足、容易被病原微生物污染、难以大量生产的缺点,人工合成材料往往亲水性还不够,而且温敏型凝胶在体内的代谢途径对组织器官的影响也尚在研究中。 ORCID: 0000-0002-9070-7602(陈泳佳) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

可注射葡萄糖酸内酯-海藻酸钠/β-磷酸三钙-聚乙二醇复合水凝胶支架的性能评价

背景:可注射海藻酸钠水凝胶可以通过非侵入性或微创方式修复骨缺损,但力学性能欠佳,聚乙二醇基水凝胶具有弹性,将材料复合有望提高水凝胶支架的机械性能及细胞生物相容性。目的:探索葡萄糖酸内酯-海藻酸钠/β-磷酸三钙-聚乙二醇复合水凝胶的理化性能,以及对鼠骨髓间充质干细胞增殖和分化的影响。方法:以葡萄糖酸内酯为交联剂,分别制备葡萄糖酸内酯-海藻酸钠/β-磷酸三钙-聚乙二醇水凝胶(交联剂的浓度分别为5,10,20 g/L,依次记为A、B、C组)与葡萄糖酸内酯-海藻酸钠/β-磷酸三钙水凝胶(交联剂的浓度为10 g/L,记为D组),表征4组水凝胶的形态、机械性能与凝胶时间。将SD大鼠骨髓间充质干细胞分别与4组水凝胶共培养,利用CCK-8法检测细胞增殖,Live/Dead荧光染色观察细胞存活情况,Ⅰ型胶原免疫细胞化学染色检测成骨分化情况。结果与结论:(1)扫描电镜下,A、B、C组可见类似黏结性的丝状结构,A组孔径分布不均匀,B组孔径分布均匀且孔隙率高,C组孔隙率高但孔径大小不一,D组孔径分布不均且孔隙率低。(2)理化性质:B组的压缩应力高于D组(P <0.05),并且随着交联剂浓度的增加,A、B...     

掺锶复合PVA/生物活性玻璃水凝胶的制备及其体外软骨修复性能研究

目的研究以聚乙烯醇(PVA)、生物活性玻璃(BG)及氯化锶为主要原料,制备的PVA水凝胶、PVA/生物活性玻璃水凝胶、掺锶复合PVA/生物活性玻璃水凝胶的可降解性能、离子释放性能和促软骨修复性能。方法PVA溶液与BG溶胶凝胶溶液在加热搅拌下生成PB水凝胶,PVA溶液与Sr-BG溶胶凝胶溶液加热搅拌生成PBSr水凝胶,将PB和PB-Sr水凝胶浸泡于磷酸盐缓冲液(PBS)中,研究其体外降解性能、离子释放性能和结构变化。在水凝胶上培养软骨细胞,经细胞增殖能力实验和细胞荧光染色观察细胞增殖情况。结果 PB和PB-Sr水凝胶在PBS溶液中逐渐降解,28 d后PB水凝胶降解率为25%,PB-Sr水凝胶降解率为16%,水凝胶表面均有羟基磷灰石形成。细胞实验结果显示培养7 d后PB-Sr水凝胶的OD值为0.76±0.04,PB水凝胶的OD值为0.52±0.02,均显著高于对照组,PVA水凝胶的OD值0.45±0.04,差异具有统计学意义(0.05)。结论该掺锶复合PVA/生物活性玻璃水凝胶具有良好的降解性能和离子释放性能,能有效促进软骨细胞增殖。     

紫杉醇PCL-PEG-PCL温敏性缓释凝胶的制备及性能研究

目的 利用聚己内酯-聚乙二醇-聚己内酯(PCL1250-PEG1500-PCL1250)两亲性聚合物温敏凝胶作为载体材料,构建疏水性抗肿瘤药物紫杉醇的载药体系.方法 以辛酸亚锡为催化剂、聚乙二醇为引发剂,引发己内酯单体开环聚合,合成PCL1250-PEG1500-PCL1250三嵌段共聚物.通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行表征:制备不同凝胶浓度及初始载药量的载药温敏凝胶,并对其相转变性能、体外药物释放行为以及体内的生物降解性能进行考察.结果 核磁共振及凝胶渗透色谱测定结果表明:合成的共聚物组成与初始投料比一致,符合设计的PCL1250-PEG1500-PCL1250嵌段聚合物结构;该凝胶在15%～30%浓度区间内,具备温敏性溶胶-凝胶相转变能力;该温敏凝胶对紫杉醇具有可控的药物缓释能力,通过改变凝胶浓度及初始载药量可调节药物释放速率和维持释放的时间.小鼠背部皮下注射PCL1250-PEG1500-PCL1250溶胶后在体内迅速原位凝胶化,凝胶随植入时间逐渐降解至45 d时基本降解完全.结论 PCL1250-PEG1500-PCL1250温敏凝胶作为紫杉醇载药体系具有良好的药物控释能力和体内生物降解性能.     

人工髓核材料-聚乙烯醇水凝胶的溶胀性能研究

利用冷冻-解冻法制得聚乙烯醇(PVA)水凝胶弹性体,研究了其用于人工髓核材料的溶胀特性,以及聚乙烯醇浓度、溶胀温度、溶胀体系的pH值对其溶胀性能的影响,采用扫描电镜对其微观形貌进行了观察,并对其溶胀动力学进行了探讨。结果表明,聚乙烯醇水凝胶是一种多孔网状结构,网络孔径大小与水凝胶中聚乙烯醇的含量有关;增加聚乙烯醇的浓度,提高溶胀温度以及溶胀体系的pH值,其平衡溶胀率减小;通过溶胀动力学方程对其溶胀过程进行了描述,水凝胶中聚乙烯醇的含量,试样尺寸以及溶胀体系的pH值,是溶胀速率快慢的重要影响因素。     

药物控释用海藻酸钠、壳聚糖、明胶的研究进展

由于许多药物如肽或蛋白质药物,物理化学性质不稳定,在胃肠道中极易降解.因此,在口服释药设计中,pH敏感水凝胶如海藻酸钠、壳聚糖和明胶作为药物控制释放载体日益引起人们的关注.将针对三种天然高分子材料的来源、结构、性能及共混改性展开讨论.     

Modified carrageenan. 2. Hydrolyzed crosslinked kappa-carrageenan-g-PAAm as a novel smart superabsorbent hydrogel with low salt sensitivity

A novel pH-responsive superabsorbing hydrogel based on K-carrageenan (kappaC) was prepared through polyacrylamide crosslinking grafting followed by alkaline hydrolysis. The hydrogel structure was confirmed using FT-IR spectroscopy. The hydrolysis conditions were systematically optimized to obtain a hydrogel with maximum swelling capacity. Thus, the reaction variables, including the hydrolysis time and temperature, concentration of sodium hydroxide, amount of hydrogel hydrolyzed and post-neutralization pH, were optimized. The swelling measurements of the hydrogels were conducted in 0.15 M aqueous solutions of LiCl, NaCl, KCI, CaCl2 and AlCl3. As observed for the hydrolyzed hydrogel (H-carragPAM), it was found that a 'charge screening' action of small cations and carboxylate anions affected the swelling in univalent salt solutions. In the case of the non-hydrolyzed hydrogel (carragPAM), however, a converse trend was observed. As a result, carragPAM and H-carragPAM superabsorbent hydrogels showed a maximum swelling of 45 and 135 g/g in LiCl and KCl solutions, respectively. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as anti-salt superabsrbents. The swelling of superabsorbing hydrogels was examined in buffer solutions with pH values ranging between 1 and 13. The H-carragPAM hydrogel exhibited a pH-responsie character so that a swelling-deswelling pulsatile behavior was recorded at pH 4 and 9. The swelling kinetics of H-carragPAM were preliminary investigated.     

Synthesis, properties and controlled release behaviors of hydrogel networks using cyclodextrin as pendant groups

Based on inclusion character of beta-cyclodextrin (beta-CD) with drug molecule and low glass transition temperature of poly(2-hydroxyethyl acrylate) (PHEA), a series of hydrogels with different compositions were synthesized by the copolymerization of a monovinyl cyclodexrin monomer with 2-hydroxyethyl acrylate (HEA). The structure and properties of the hydrogels were characterized by FTIR, DSC, TGA and swelling measurements. It is found that swelling ratios of these beta-CD hydrogels can keep a relative stability in the range of pH from 1.4 to 7.4, and are not sensitive to change in NaCl concentration. Using drug N-acety-5-methoxytryptamine (melatonin, MEL) as a model molecule, the controlled drug release behaviors of these hydrogels were investigated. The results indicate that the diffusion and permeation of MEL from the hydrogels may be a dominant factor for its release. Owing to the formation of MEL/beta-CD retarding diffusion rate of MEL, a sustained release of MEL from hydrogel with high content of beta-CD can be obtained compared with hydrogel PHEA without beta-CD.     

Modified carrageenan. 2. Hydrolyzed crosslinked κ-carrageenan-g-PAAm as a novel smart superabsorbent hydrogel with low salt sensitivity

A novel pH-responsive superabsorbing hydrogel based on κ-carrageenan (κC) was prepared through polyacrylamide crosslinking grafting followed by alkaline hydrolysis. The hydrogel structure was confirmed using FT-IR spectroscopy. The hydrolysis conditions were systematically optimized to obtain a hydrogel with maximum swelling capacity. Thus, the reaction variables, including the hydrolysis time and temperature, concentration of sodium hydroxide, amount of hydrogel hydrolyzed and post-neutralization pH, were optimized. The swelling measurements of the hydrogels were conducted in 0.15 M aqueous solutions of LiCl, NaCl, KCl, CaCl₂ and AlCl₃. As observed for the hydrolyzed hydrogel (H-carragPAM), it was found that a 'charge screening' action of small cations and carboxylate anions affected the swelling in univalent salt solutions. In the case of the non-hydrolyzed hydrogel (carragPAM), however, a converse trend was observed. As a result, carragPAM and H-carragPAM superabsorbent hydrogels showed a maximum swelling of 45 and 135 g/g in LiCl and KCl solutions, respectively. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as anti-salt superabsrbents. The swelling of superabsorbing hydrogels was examined in buffer solutions with pH values ranging between 1 and 13. The H-carragPAM hydrogel exhibited a pH-responsie character so that a swelling-deswelling pulsatile behavior was recorded at pH 4 and 9. The swelling kinetics of H-carragPAM were preliminary investigated.     

pH-modulated release of insulin entrapped in a spontaneously formed hydrogel system composed of two water-soluble phospholipid polymers

To develop a polypeptide drug carrier through oral administration, a polymer hydrogel has been found that is very easy to prepare by mixing two water-soluble phospholipid polymers. The polymers having 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties spontaneously formed a hydrogel, which showed controllable dissociation via pH changes. In this study, the MPC polymer hydrogel was prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB), and the applicability of the hydrogel as an oral drug delivery carrier was examined. The gelation process from the two MPC polymers is spontaneous, requiring no chemical reactions and/or no physical stimuli. PMB has a hydrophobic domain, which is suitable for loading hydrophobic drugs. Insulin could be very easily loaded to almost 100% in the hydrogel. PMA also has carboxyl groups, which are well known for pH sensitivity. At pH 1.8, the swelling continued for 8 h, with complete dissociation after 16 h. At pH 6.8, the hydrogel completely dissociated within 4 h. The hydrogel remained stable at pH 1.8 and released all the insulin at pH 6.8. The release rate was approximately four times faster at pH 6.8. After release, the insulin did not show any denaturing tendency.     

pH-modulated release of insulin entrapped in a spontaneously formed hydrogel system composed of two water-soluble phospholipid polymers

To develop a polypeptide drug carrier through oral administration, a polymer hydrogel has been found that is very easy to prepare by mixing two water-soluble phospholipid polymers. The polymers having 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties spontaneously formed a hydrogel, which showed controllable dissociation via pH changes. In this study, the MPC polymer hydrogel was prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB), and the applicability of the hydrogel as an oral drug delivery carrier was examined. The gelation process from the two MPC polymers is spontaneous, requiring no chemical reactions and/or no physical stimuli. PMB has a hydrophobic domain, which is suitable for loading hydrophobic drugs. Insulin could be very easily loaded to almost 100% in the hydrogel. PMA also has carboxyl groups, which are well known for pH sensitivity. At pH 1.8, the swelling continued for 8 h, with complete dissociation after 16 h. At pH 6.8, the hydrogel completely dissociated within 4 h. The hydrogel remained stable at pH 1.8 and released all the insulin at pH 6.8. The release rate was approximately four times faster at pH 6.8. After release, the insulin did not show any denaturing tendency.     

Magnetic/pH-sensitive κ-carrageenan/sodium alginate hydrogel nanocomposite beads: preparation,swelling behavior,and drug delivery

This work describes the preparation of magnetic and pH-sensitive beads based on κ-carrageenan and sodium alginate for use as drug-targeting carriers. Physical cross-linking using K⁺/Ca²⁺ ions was applied to obtain ionic cross-linked magnetic hydrogel beads. The produced magnetite beads were thoroughly characterized by TEM, SEM/EDS, XRD, FTIR, and VSM techniques. While the water absorbency (WA) of magnetic beads was enhanced by increasing the weight ratio of κ-carrageenan, introducing magnetic nanoparticles caused a decrease in WA capacity from 15.4 to 6.3 g/g. Investigation on the swelling of the hydrogel beads in NaCl, KCl, and CaCl₂ solutions revealed the disintegration of beads depending on the composition of hydrogel beads and the type of metal cations in swelling media. The swelling ratio of beads indicated pH-dependent properties with maximum water absorbing at pH 7.4. Also, it was found that the strength of pH-sensitivity of magnetic beads was low for beads with the high content of carrageenan component. The in vitro drug release studies from hydrogels exhibited significant behaviors on the subject of physiological-simulated pH values and external magnetic fields. The maximum cumulative releases obtained were 98 and 43% at pH values 7.4 and 1.2, respectively. The Introducing magnetite nanoparticles influenced the cumulative release of drug.     

Swelling characteristics and drug delivery properties of nifedipine-loaded pH sensitive alginate-chitosan hydrogel beads

The aim of the present work was to investigate the swelling behavior and in vitro release of nifedipine from alginate-chitosan hydrogel beads. Structure and surface morphology of the hydrogel were characterized by FTIR and SEM, respectively. Alginate-chitosan mixed beads and alginate-chitosan coated beads were prepared by ionic gelation method. The swelling ability of the beads and in vitro release of nifedipine in simulated gastric fluid (pH 1.5) and different phosphate buffer solutions (pH 2.5, 5.0, 6.8, 7.4, and 8.0) were found to be dependent on the presence of the polyelectrolyte complex between chitosan and alginate. The amount of nifedipine released from the mixed beads at pH 1.5 was relatively low (42%), whereas this value approached to 99% at pH 6.8. In comparison with the mixed beads, the released nifedipine from the coated beads was minimal at pH 1.5 (18%), whereas approximately 99% nifedipine was released at pH 6.8. The results suggested that the coated beads can hold drug better at low pH than the mixed beads and show excellent pH sensitivity. Therefore, the alginate-chitosan coated beads could be a suitable polymeric carrier for drug delivery in the intestinal tract.     

Biodegradable pH/temperature-sensitive oligo(β-amino ester urethane) hydrogels for controlled release of doxorubicin

An injectable biodegradable pH/temperature-sensitive oligo(β-amino ester urethane) (OAEU) was synthesized. The OAEU was synthesized by addition polymerization between the isocyanate groups of 1,6-diisocyanato hexamethylene and the hydroxyl groups of a synthesized monomer piperazine dihydroxyl amino ester (monomer PDE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized OAEU was characterized by (1)H NMR spectroscopy, Fourier transform infrared spectroscopy and gel permeation chromatography. The aqueous solutions of OAEU showed a sol-to-gel-to-sol phase transition as a function of temperature and pH. The gel window covered the physiological conditions (37°C, pH 7.4) and could be controlled by changing the OAEU concentration. After a subcutaneous injection of the OAEU solution into Sprague-Dawley rats, a gel formed rapidly in situ and remained in the body for more than 2 weeks. The in vitro cytotoxicity test and in vitro degradation showed that the OAEU hydrogel was non-cytotoxic and biodegradable. The in vitro release of doxorubicin from this OAEU hydrogel was sustained for more than 10 days. This injectable biodegradable pH/temperature-sensitive OAEU hydrogel is a potential candidate as a drug/protein carrier and in biomedical applications.     

Preparation and Characterization of pH-Sensitive Anionic Hydrogel Microparticles for Oral Protein-Delivery Applications

pH-sensitive P(MAA-g-EG) anionic hydrogel microparticles having an average diameter of approx. 4 μm were prepared by suspension photopolymerization. The pH-sensitive swelling and release behaviors of the P(MAA-g-EG) hydrogel microparticles were investigated as a biological on–off switch for the design of an oral protein delivery system triggered by external pH changes in the human GI tract. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-g-EG) particles at a pH of around 5, which is the pK _a of PMAA. At pH < 5, the particles were in a relatively collapsed state, while at a pH > 5 the particles swelled to a high degree. When the concentration of the cross-linker of the hydrogel increased, the swelling ratio of the P(MAA-g-EG) hydrogel microparticles decreased at a pH higher than 5 and the pK _a of all the microparticles was in the pH range 4.0–6.0. In release experiments using Rhodamine B (Rh-B) as a model solute, the P(MAA-g-EG) hydrogel microparticles showed a pH-responsive release behavior. At low pH (pH 4.0) only a small amount of Rh-B was released while at high pH (pH 6.0) a relatively large amount of Rh-B was released from the hydrogel particles.