NIPAAm系互穿网络凝胶的合成及载药释药性能研究

合成了三种亲疏水性不同的温度及pH敏感的PAAc／P（NIPAAm-co-BMA）、PAAc／PNIPAAm和PAAc／P（NIPAAm-co-AAm）互穿网络（IPN）水凝胶,以水杨酸钠和水杨酸为模型药物,研究了温度、pH值及药物和凝胶的亲疏水性相互作用对模型药物释药性能的影响。研究结果表明,随着凝胶亲水性的增强,水杨酸钠的载药率提高,释药率也越大;相反疏水性增强也有利于提高水杨酸的载药率;IPN凝胶在水中的释药过程属于溶胀支配型释放,药物释放率随凝胶的亲水性增强而增强,同时,载药凝胶在45℃水中的释药率大于25℃时的释药率。在25℃时,水杨酸在pH=2．2的缓冲溶液中几乎不释放,而在pH=7．4的缓冲溶液中能以较快的速率释放。     

可酶降解的温度及pH敏感水凝胶的制备及对牛血清白蛋白的吸附和释放

以4,4'-二甲基丙烯酰氨基偶氮苯(BMAAB)为偶氮交联剂,制备了可酶降解的N-异丙基丙烯酰胺(NIPAAm)-丙烯酸(AA)共聚物水凝胶. 结果表明,研究的凝胶均表现出在4 ℃和37 ℃之间的溶胀相转变. 以牛血清白蛋白(BSA)为模型药物,在pH=7.4的缓冲溶液中对BSA进行了负载. 结果表明,凝胶在4 ℃时对BSA的负载量为144.5 mg(BSA)/g(gel),37 ℃为14.8 mg(BSA)/g(gel). 凝胶在pH=7.4的缓冲溶液中,在结肠菌作用下能发生酶降解,药物累积释放量4 d可达100 mg(BSA)/g干胶.     

基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能

在离子液体均相体系中合成了一种新型两亲性窄分子量分布的低聚壳聚糖衍生物月桂基-琥珀酰化壳聚糖(LSCOS). 以LSCOS为载体材料, 以牛血清蛋白(BSA)为模板蛋白, 以戊二醛为交联剂, 用油包水(W/O)乳化交联法制备了包载BSA的BSA/LSCOS缓释载药微球. 通过扫描电子显微镜(SEM)、 透射电子显微镜(TEM)及紫外-可见光谱(UV-Vis)研究了BSA/LSCOS比率和戊二醛/LSCOS比率对微球的形貌结构、 包埋率、 载药率和体外药物释放特性的影响. 结果表明, 在离子液体中合成的LSCOS包覆了BSA, 形成的微球粒径约为1 μm, 微球表面随BSA用量的增加变得光滑, 随戊二醛用量的增加变得粗糙. BSA的累积释放率与BSA包载量成正比, 与交联剂添加量成反比, 因此, 可通过控制蛋白质药物的添加比率和交联剂用量来控制蛋白质药物体外释放率.     

聚(N-异丙基丙烯酰胺)/聚丙烯酰胺无机/有机互穿网络水凝胶的制备及表征

通过紫外引发聚合方法制备了无机交联的聚(N-异丙基丙烯酰胺)(PNIPAAm)/有机交联的聚丙烯酰胺(PAAm)互穿网络(IPN)水凝胶.利用FTIR和SEM分别表征了凝胶的化学结构和内部形态;测定了凝胶在高温(50℃)时的退溶胀性能;利用DMA和DSC分别研究了凝胶的储能模量随温度的变化及热相转变行为.研究表明,该IPN凝胶具有温度敏感性;与未互穿的无机交联PNIPAAm凝胶相比,IPN凝胶具有多孔的网络结构和超快的响应速率,如10min内失去90%的水;其储能模量增加了3～4倍,相转变行为变弱,而最低临界溶解温度(LCST)提高了1.4℃.     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

温度和pH敏感P（NIPA／AA）／黏土互穿网络水凝胶的辐射合成与表征

以N-异丙基丙烯酰胺(NIPA)和丙烯酸(AA)为聚合单体、有机黏土作为改性剂,采用60Co-γ射线为放射源,辐射合成了P(NIPA/AA)/黏土互穿网络(IPN)水凝胶,研究了IPN的表面形貌以及AA浓度、黏土对水凝胶溶胀性能和压缩性能的影响.SEM电镜观察表明:P(NIPA/AA)共聚水凝胶的表面致密,没有明显相分离,而IPN凝胶表面疏松多孔且非连续,有明显的相分离,形成了较好的IPN结构.P(NIPA/AA)IPN水凝胶在碱性和弱碱性溶液中的溶胀率高,且其溶胀速率由网络中高分子链的松弛运动控制;而在酸性介质中,水分子的扩散为水凝胶溶胀的决定过程.P(NIPA/AA)IPN水凝胶具有良好的力学性能,加入黏土后凝胶的压缩性能参数均有不同程度的提高,水凝胶受压时只发生塑性变形,没有被破坏.     

聚丙烯酸钠和丝素蛋白自膨胀水凝胶的制备及其释药性能

通过自由基聚合的方法合成制备了自膨胀PAAS-SF semi-IPN水凝胶(聚丙烯酸钠-丝素半互穿网络水凝胶),并进一步探讨其作为微创治疗中组织植入物的潜能.主要研究了SF(丝素蛋白)和AA(丙烯酸)的重量比对PAAS-SFsemi-IPN水凝胶的结构、膨胀性以及力学性能的影响.此外,我们还研究了抗生素药物阿莫西林(AMO)在PAAS-SFsemi-IPN水凝胶中的包载与释放性能.结果表明,随着水凝胶中SF含量的增加,膨胀率增大,压缩强度减小,药物释放速率加快,且PAAS-SF20 semi-IPN水凝胶在120 h内能释放(83.4±0.9)%的药物.所开发的自膨胀PAAS-SFsemi-IPN水凝胶具有高膨胀率和良好的药物释放能力,将在药物输送或其它植入材料领域有良好的应用前景.     

P(AA-co-PEGLA)凝胶对吡罗昔康的控释作用

将两亲性大单体聚氧乙烯月桂醇醚丙烯酸酯(PEGLA)与丙烯酸(AA)通过UV引发聚合,制备了水凝胶P(AA-CO-PEGLA).以水难溶性吡罗昔康为模型药物,研究了凝胶中PEGLA含量对栽药量的影响.结果表明;吡罗昔康的栽药量随着PEGLA含量的增加而提高,当凝胶中的PEGLA的摩尔分数(x)从0增加到60%时,载药量从1.24 mg/g提高到17.36 mg/g.吡罗昔康体外释放研究表明:P(AA-co-PEGLA)凝胶可保护药物不被胃酸等破坏,而在肠中释放.药物的释放速率随着凝胶中PEGLA含量的增加而降低,表现出明显的缓释作用.用Weibull方程拟合释放曲线,指数因子(b)0.88～0.97,表明对吡罗昔康释放的控制是扩散和高分子链松弛协同作用的结果.     

温敏性PCL-PEG-PCL水凝胶的合成、表征及蛋白药物释放

考察了温敏性PCL-PEG-PCL水凝胶中聚乙二醇(PEG)及聚己内酯(PCL)不同嵌段组成对其溶胶-凝胶相转变温度以及亲水性药物(牛血清白蛋白, BSA)释放速率的影响. 采用开环聚合法, 以辛酸亚锡为催化剂、PEG1500/PEG1000为引发剂, 与己内酯单体发生开环共聚, 合成了一系列具有不同PEG和PCL嵌段长度的PCL-PEG-PCL型三嵌段共聚物. 通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行了表征. 共聚物的溶胶-凝胶相变温度由翻转试管法测定. 利用透射电镜、核磁共振氢谱及荧光探针技术证实了该材料在水溶液中胶束的形成. 以BSA为模型蛋白药物, 制备载药水凝胶, 利用microBCA法测定药物在释放介质中的浓度, 研究其体外释放行为. 实验结果表明, 共聚物的溶胶-凝胶相变温度与PCL及PEG嵌段长度紧密相关, 即在给定共聚物浓度情况下, 固定PEG嵌段长度而增加PCL嵌段长度, 会导致相变温度降低; 而固定PCL嵌段长度而增加PEG嵌段长度, 其相变温度相应升高. 水凝胶中蛋白药物的释放速率与疏水的PCL嵌段长度无关, 而与亲水的PEG嵌段长度密切相关, 即PEG嵌段越长, 蛋白药物释放越快.     

PEGDA/NIPAM共聚物水凝胶的药物释放性能研究

以IRGACURE2959为光引发剂,聚乙二醇双丙烯酸酯(PEGAD)和N-异丙基丙烯酰胺(NIPAM)为单体,通过紫外光引发光聚合,合成了PEGDA/NIPAM共聚物水凝胶,研究了凝胶于不同酸度介质及不同温度中对阿司匹林的释放行为。结果表明,模拟胃肠液中,随释放时间的延长,载药凝胶对药物的累积释放率增加。NIPAM单体的引入增大药物累积释放率,药物缓释时间延长,具有良好的药物释放性能。凝胶对药物的缓释受温度与释放时间的影响,在37℃和45℃时,随释放时间增加,药物累积释放率增大;在30℃时,随释放时间的增长,累积释放率先增大后减小。     

疏水/亲水性聚二乙烯基苯/聚丙烯酸大孔互穿聚合物网络树脂对苯胺的吸附性能

采用分步悬浮聚合法制备了聚二乙烯基苯/聚丙烯酸甲酯（PDVB/PMA）大孔互穿聚合物网络,将其中的聚丙烯酸甲酯转化为聚丙烯酸,得到具有疏水/亲水性能的聚二乙烯基苯/聚丙烯酸（PDVB/PAA）大孔互穿聚合物网络（IPN）,研究了这类疏水/亲水大孔PDVB/PAA IPN对苯胺的吸附热力学和吸附动力学,测定了该树脂的孔结构、含水量、弱酸交换量和溶胀性能;测定了该树脂对苯胺在不同温度下的吸附等温线,利用热力学函数关系计算了吸附焓、自由能和熵。 红外光谱显示,成功合成了疏水/亲水PDVB/PAA IPN,与PDVB、PDVB/PMA IPN树脂相比,其BET表面积以及孔容均减小,含水量为62.73％,弱酸交换量为1.91 mmol/g;对苯胺的吸附为放热、自发的过程;溶胀实验、静态解吸实验表明,PDVB/PAA IPN树脂中疏水性的PDVB网具有疏水作用吸附能力,亲水性的PAA网具有氢键作用吸附能力。 对苯胺的吸附在90 min时即可达到吸附平衡,树脂吸附苯胺符合一级速率方程,吸附速率主要受颗粒内扩散的控制,同时还受液膜扩散的影响,吸附动力学可采用HSDM模型描述。     

Characterization of a planar poly(acrylic acid) brush as a materials coating for controlled protein immobilization

The adsorption of two different proteins at a planar poly(acrylic acid) (PAA) brush was studied as a function of the ionic strength of the protein solutions applying total internal reflection fluorescence (TIRF) spectroscopy. Planar PAA brushes were prepared with a grafting density of 0.11 nm(-2) and were characterized using X-ray reflectometry. Hen egg-white lysozyme and bovine serum albumin (BSA) were used as model proteins, which have a net positive and negative charge at neutral pH-values, respectively. It has been found that both proteins adsorb strongly at a planar PAA brush at low ionic strength. Whereas lysozyme interacts with a PAA brush under electrostatic attraction at neutral pH-values, BSA binds under electrostatic repulsion at pH > 5. Even at pH = 8, significant amounts of BSA are adsorbed to a planar PAA brush. In addition, the reversibility of BSA adsorption has been characterized. Dilution of a BSA solution leads to an almost complete desorption of BSA from a PAA brush at short contact times. When the ionic strength of the protein solutions is increased to about 100-200 mM, a planar PAA brush appears largely protein-resistant, regardless of the protein net charge. The results of this study indicate that the salt-dependent protein affinity of a PAA brush represents a unique effect that must be explained by a novel protein-binding mechanism. On the basis of a recent model, it is suggested that a release of counterions is the most probable driving force for protein adsorption at a PAA brush. In a general view, this study characterizes a planar PAA brush as a new materials coating for the controlled immobilization of proteins whose use in biotechnological applications appears to be rewarding.     

负载蛋白质的胶原/聚两性电解质IPN角膜替代物

以碳二亚胺/N-羟基琥珀酰亚胺(EDC/NHS)和聚乙二醇二丙烯酸酯(PEGDA)为交联剂分别对猪皮去端肽Ⅰ型胶原和3-(甲基丙烯酰胺)丙基-二甲基(3-磺丙)胺(MPDSAH)进行交联, 制备了具有互穿聚合物网络(IPN)结构的角膜替代物. 胶原基IPN角膜替代物的折光指数和白光透过率与天然人角膜相似. IPN水凝胶具有优于纯胶原凝胶的力学性能, 同时PMPDSAH网络的引入明显提高了IPN凝胶在胶原酶中的稳定性. 体外细胞培养实验结果表明, IPN角膜替代物支持人角膜上皮细胞生长. 通过冷冻干燥-溶胀后包覆技术可将牛血清白蛋白(BSA)和神经生长因子(NGF)装载到角膜替代物中, 负载药物的冻干凝胶可干态保存, 避免了湿态下蛋白质等活性因子的失活和漏泄; 再吸水恢复原状的特性可使角膜替代物完好地移植病灶部位, NGF具有良好的缓释效果. 此负载NGF的复合角膜替代物有望促进角膜组织和神经的再生.     

壳聚糖·聚丙烯酸配合物半互穿聚合物网络膜及其对pH和离子的刺激响应

壳聚糖·聚丙烯酸配合物半互穿聚合物网络膜及其对ｐＨ和离子的刺激响应李文俊王汉夫卢玉华汪志亮钟伟（复旦大学高分子科学系聚合物分子工程开放实验室上海２００４３３）关键词高分子间配合物，互穿聚合物网络（ＩＰＮ），水凝胶，壳聚糖，刺激响应敏感性水凝胶是一种...     

Antimicrobial loading into and release from poly(ethylene glycol)/poly(acrylic acid) semi‐interpenetrating hydrogels

Electrostatic interactions within a semi‐interpenetrating network (semi‐IPN) gel can control the postsynthesis loading, long‐term retention, and subsequent release of small‐molecule cationic antibiotics. Here, electrostatic charge is introduced into an otherwise neutral gel [poly(ethylene glycol) (PEG)] by physically entrapping high‐molecular‐weight poly(acrylic acid) (PAA). The network structure is characterized by small‐angle neutron scattering. PEG/PAA semi‐IPN gels absorb over 40 times more antibiotic than PAA‐free PEG gels. Subsequent soaking in physiological buffer (pH 7.4; 0.15 M NaCl) releases the loaded antibiotics for periods as long as 30 days. The loaded gels elute antibiotics with diffusivities of 4.46 × 10^?8 cm²/s (amikacin) and 2.08 × 10^?8 cm²/s (colistin), which are two orders of magnitude less than those in pure PEG gels where diffusion is controlled purely by gel tortuosity. The release and hindered diffusion can be understood based on the partial shielding of the charged groups within the loaded gel, and they have a significant effect on the antimicrobial properties of these gels. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 64–72     

Synthesis and Properties of IPN Hydrogels Based on Konjac Glucomannan and Poly（acrylic acid）

As a random copolymer of β-(1,4) linked D-mannose and D-glucose, konjac gluco- mannan (KGM) is a naturally occurring water-soluble polysaccharide, and has been paid attention in the field of drug controlled release carriers potentially used in colon1,2. …     

基于互穿网络结构的pH/温度双重刺激响应性微凝胶的研究

室温下采用氧化-还原引发体系,以低交联密度的聚(N-异丙基丙烯酰胺)(PNIPAM)微凝胶为种子,通过种子乳液聚合法合成由PNIPAM和聚丙烯酸(PAA)形成的具有互穿聚合物网络结构的微凝胶.傅立叶变换红外光谱分析结果表明微凝胶由PNIPAM和PAA两种聚合物组成,透射电镜表征结果证实微凝胶中PNIPAM和PAA两种聚合物形成了互穿网络结构.用动态激光光散射测试不同温度或pH值水介质中微凝胶的粒径,结果发现微凝胶具有良好的pH/温度双重刺激响应性.在水介质pH值大于5.5的情况下,PAA组分对微凝胶的体积相转变温度没有影响;而在水介质pH值为4.0的情况下,由于PAA与PNIPAM之间的氢键作用,微凝胶的体积相转变温度稍微降低.微凝胶中PAA组分含量越高,其pH刺激响应性越显著.     

Preparation of albumin—PAA nanocapsules and their controlled release behavior for drugs

New kinds of narrowly distributed protein‐based nanoparticles, bovine serum albumin‐Poly (acrylic acid) (BSA/PAA) nanospheres, and nanocapsules were prepared via in situ polymerization, swelling, and re‐aggregation. The structure and morphology of the nanospheres were characterized by UV‐Vis, FT‐IR, DLS, and TEM. The stability of the BSA/PAA nanospheres and nanocapsules was increased when their skeletons were fixed by cross‐linked agents. The nanospheres carried a positive charge and their size was about 80–110 nm. The protein‐based nanocapsules were stimuli‐responsive with pH value and their hydrodynamic diameter varied from 70 to 230 nm with changes of pH. In vitro release experiments of Rhodamine B and Doxorubicin hydrochloride showed that these biopolymer nanoparticles provided a controlled release of the entrapped drugs for 300 hr. Copyright © 2009 John Wiley & Sons, Ltd.     

Structure and protein binding capacity of a planar PAA brush

We performed neutron reflectometry (NR) and total internal reflection fluorescence (TIRF) spectroscopy to characterize the structure and the protein binding capacity of a planar poly(acrylic acid) (PAA) brush at different temperatures. A PAA brush was prepared by spin-coating planar quartz or silicon wafers with a thin film of poly(styrene). Then, the diblock copolymer poly(styrene)-poly(acrylic acid) was deposited on these modified wafers using the Langmuir-Sch?fer or Langmuir-Blodgett technique. PAA grafting densities of about 0.1 chains per nm2 were obtained. The NR experiments indicate a remarkable swelling of the PAA brush in contact with a buffer solution, when it is heated to 40 degrees C for several hours. The swollen brush structure remains upon cooling back to 20 degrees C suggesting a disentanglement of the initially formed PAA brush by the temporary heating. At pD = 6.7, the protein bovine serum albumin (BSA) with a negative net charge is strongly adsorbed to the swollen PAA brush. From the scattering length density profiles obtained from the NR curves, an almost homogeneous filling of the whole PAA brush space with BSA molecules can be deduced corresponding to an average BSA volume fraction of about 7-10% and an adsorbed protein mass of about 1.4 mg m-2. By analyzing the TIRF experiments, it is found that BSA adsorption is enhanced when increasing the temperature which represents an evidence for an entropic driving force for protein adsorption. However, the mechanism of BSA adsorption at a PAA brush appears to be different at 20 and 40 degrees C.     

pH-Controllable drug release using hydrogel encapsulated mesoporous silica

Amine-functionalized mesoporous SBA-15 silica loaded with bovine serum albumin (BSA) has been successfully encapsulated with a thin layer coating of poly(acrylic acid) PAA, with the entrapped BSA being released from the PAA-encapsulated SBA-15 at the higher pH value of 7.4 rather than at the lower pH value of 1.2. This novel drug delivery system has a potential application in the release of protein drug to the site of higher pH value, such as small intestine or colon.