羧甲基壳聚糖水凝胶制备及其在药物控释中的应用

以戊二醛为交联剂制备了一系列羧甲基壳聚糖pH敏感水凝胶 .研究了合成条件对羧甲基壳聚糖水凝胶溶胀性能的影响 .实验结果表明羧甲基壳聚糖的脱乙酰度、交联剂用量对水凝胶溶胀率的影响较大 .pH=3 0时 ,水凝胶收缩 ,而pH =1 0 ,5 0 ,7 4 ,9 0时 ,水凝胶溶胀 ,且在碱性条件下水凝胶的溶胀率远大于酸性条件下的溶胀率 .包埋在此水凝胶中的水杨酸释放随载药介质的pH值和水凝胶半径大小的变化而显著不同 ,pH =1 0条件下载药的水凝胶的释药率大于pH =7 4 ,12 0条件下的释药率 ,且水凝胶的半径越大 ,释药速度和释药率也越大     

基于埃洛石的载药凝胶小球的制备及性能研究

采用离子凝胶法制备了一种新的壳聚糖-g-聚丙烯酸/埃洛石/海藻酸钠(CTS-g-PAA/HT/SA)凝胶小球。研究了HT含量对载药凝胶小球的溶胀性、包封效率和释放性能等的影响;同时也讨论了凝胶小球的pH敏感性和双氯芬酸钠(DS)的释放行为。结果表明:HT含量对载药凝胶小球的溶胀率、包封效率和累积释放率有明显的影响,在HT含量为30%时,溶胀率、包封效率和12h累积释放率分别达到32.84%、91.07%和100%;另外,载药凝胶小球具有较好的pH敏感性;在pH=2.1的释放介质中DS几乎不释放,而在pH=6.8的释放介质中缓慢释放;DS释药机理为溶胀控释。     

PVP-P(AAEA-co-AA)/纳米金温度-电场双重敏感性凝胶的制备及性能

采用溶液聚合法以聚乙烯吡咯烷酮(PVP)为第二网络,以丙烯酸(AA)、4-乙酰基丙烯酰乙酸乙酯(AAEA)为单体制备PVP-P(AAEA-co-AA)半互穿水凝胶(PVP-SIPN),再通过原位还原法合成PVP-P(AAEA-co-AA)/纳米金复合凝胶(GNPs gel),探讨凝胶的溶胀/消溶胀性能、温度及电场敏感性。研究表明,随PVP用量的增加PVP-SIPN溶胀速率减小,平衡溶胀度降低;当PVP用量低于5%凝胶保水率随PVP用量增加而降低,高于5%时保水率随PVP用量增加而增加;PVP-SIPN相转变温度升高,且凝胶温度敏感性随之减弱。纳米金的加入导致凝胶平衡溶胀度从82.3g/g降低至22.66g/g,在电场作用下,外界离子浓度小于0.2mol/L时,GNPs gel发生溶胀;反之,消溶胀,凝胶消溶胀速率随外界电压增大而增大。     

N-(2-磺酸基苯甲基)壳聚糖的合成、表征及其水凝胶的pH敏感性

通过两步反应合成了水溶性的N-(2-磺酸基苯甲基)壳聚糖(SBCS), 用IR, 1H NMR和UV-Vis谱对产物的结构进行了表征. 用胶体滴定法测定了N上2-磺酸基苯甲基的取代度. 以戊二醛为交联剂制备了N-(2-磺酸基苯甲基)壳聚糖水凝胶(SBCSG), 考察了凝胶在不同pH值缓冲溶液中的溶胀行为. 实验结果表明, SBCSG溶胀度随着凝胶交联度的增大而减小. 在碱性介质中SBCSG的溶胀度显著增大, 而在酸性介质中溶胀度显著减小, 在pH= 5.0缓冲液中的溶胀度达到最小值. SBCSG在碱性介质中的溶胀度随着侧链N上2-磺酸基苯甲基取代度增大而增大. 在pH=7.4的人工肠液和pH=1.0的人工胃液中SBCSG的溶胀-收缩具有可逆性, 显示出良好的pH敏感性. 有望作为pH敏感口服结肠定位给药系统药物载体.     

壳聚糖水凝胶微球的制备与溶胀性能

采用三聚磷酸钠(TPP)和六偏磷酸钠(SHMP)为复合交联剂,制备了离子交联网络结构的壳聚糖水凝胶微球。分析讨论了交联剂质量配比、pH以及离子强度等对壳聚糖微球溶胀性能的影响。结果表明:使用复合交联剂制备的微球的溶胀度比单独使用TPP或SHMP的分别低62.4%和41.3%,交联效率得到明显提高;当m(TPP)∶m(SHMP)=3∶5,交联剂pH=5时,制备的微球交联程度最好,结构最密实;在pH=1.2的缓冲溶液中,溶胀度可达到357%,而且凝胶没有任何破碎。微球具有较好的离子强度和pH敏感性,在酸性介质中有较高的溶胀度。     

羧甲基壳聚糖/海藻酸钠半互穿网络水凝胶的制备及性能研究

以羧甲基壳聚糖(CMC)和海藻酸钠(SA)为原料,京尼平(GP)为交联剂,制备具有pH敏感性的CMC/SA半互穿网络(semi-IPN)水凝胶.利用特性黏数、红外光谱对CMC/SA水凝胶的半互穿网络结构及形成机理进行了分析与表征;对水凝胶的力学性能进行了测试;探讨了pH值及交联剂含量对水凝胶溶胀性能的影响.结果表明,京尼平交联的CMC/SA水凝胶具有半互穿网络结构.当w(CMC)∶w(SA)=5∶5时,CMC/SA水凝胶的断裂强度达到最大值(59 MPa),分别比纯的CMC(40 MPa)和SA(36 MPa)提高了47.5%和63.9%;当SA含量为60%时,CMC/SA水凝胶的断裂伸长率达到最大值(13.0%).当pH3.0时,溶胀率随pH值的增大而减小,pH=3.0时,溶胀率最小(186%);当pH3.0时,溶胀率随pH值的增大而增大,pH=9.0时,溶胀率最大(886%).京尼平交联的CMC/SA半互穿网络水凝胶具有明显的pH敏感性、溶胀可逆性及对pH的快速响应性.     

粉煤灰复合聚丙烯酸钠凝胶的制备及其溶胀性能

粉煤灰(CFA)存在的情况下,采用自由基溶液聚合法,以过硫酸钾(KPS)为引发剂,N,N'-亚甲基双丙烯酰胺(NNMBA)为交联剂,制备了粉煤灰复合聚丙烯酸钠凝胶(CFAPAANa)。 以丙烯酸单体质量为基准,当交联剂用量为0.08%,引发剂用量为0.4%,粉煤灰用量为3%,丙烯酸中和度为70%,聚合温度为70 ℃时,所合成的粉煤灰复合聚丙烯酸钠凝胶在蒸馏水和生理盐水中平衡溶胀比最高,分别为1556(g/g)和168(g/g)。 考察了复合凝胶在不同介质溶液中的溶胀动力学,保水性能以及在土壤中的降解行为。 溶胀动力学研究表明,蒸馏水中溶胀初期复合凝胶聚合物链段的扩散运动能够调控凝胶溶胀的快慢及程度,而生理盐水中水分子的平移和对流运动在凝胶的溶胀过程中起着关键性作用。 保水和降解实验结果表明,25 ℃时,50 h凝胶保水率为64%,土壤中50 d时降解率达60%。 相比于聚丙烯酸钠凝胶,粉煤灰复合凝胶保水率提高了8%。     

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...     

壳聚糖-聚丙烯酸复合水凝胶的药物控制释放行为

以壳聚糖(Cs)和丙烯酸(AA)为原料,利用自由基聚合法制备了具有孔洞结构的复合水凝胶Cs-PAA,并研究了AA的量、交联剂的量、聚合温度和AA的中和度对水凝胶溶胀度的影响以及复合水凝胶对烟酸的控制释放。 结果表明,Cs-PAA复合水凝胶具有良好的pH值、离子强度敏感性,且溶胀度最高达1228 g/g,其在pH=686的缓冲溶液中的烟酸累积释放率明显大于其在pH=1.80的缓冲溶液,因此Cs-PAA水凝胶可作为肠口服药物的载体。     

聚乙烯醇/丙烯酸共聚物水凝胶的制备及溶胀性

制备了具有pH敏感性的聚乙烯醇(PVA)/丙烯酸(AA)共聚物水凝胶,研究了PVA与AA之间配比、交联剂、引发剂用量对凝胶转化率的影响,对水凝胶的溶胀行为和pH敏感性也进行了详细研究.实验表明PVA与AA的质量比为(1∶9)~(3∶7)之间时,引发剂和交联剂分别为PVA和AA总量的0.2%和0.3%时,凝胶转化率高.随着水溶液pH值从3增加到9,凝胶的溶胀比也相应的增加,表现出明显的pH敏感性.     

Design, synthesis and characterization of a novel pH-sensitive hydrogel

A novel degradable pH-sensitive hydrogel with pendent carboxyl groups was designed and synthesized from ethylenediaminetetraacetic dianhydride （EDTAh） and butanediamine （BDA） with dicyclohexylcarbodiimide （DCC） as a condensating agent and BDA as a crosslinking agent. The obtained polymers were characterized by ^13C NMR, ^1H NMR and FTIR. The swelling experiments of the hydrogel in pH 3, 7, and 12 media indicated much higher swelling ratio in pH 12 media than in pH 3 and pH 7 media, exhibiting sound pH sensitivity. The pH sensitivity of this type of hydrogel may be regulated through controlling the type and the dose of the crosslinking agent.     

Synthesis,characterization and evaluation of semi‐IPN hydrogels consisted of poly(methacrylic acid) and guar gum for colon‐specific drug delivery

The semi‐IPN hydrogels consisting of poly(methacrylic acid) and guar gum (GG) are prepared at room temperature using water as solvent. 5‐aminosalicylic acid (5‐ASA) is entrapped in the hydrogel in the synthesis of hydrogel and all entrapment efficiencies are found above 85%. The hydrogel shows excellent pH‐sensitivity. It exhibited minimum swelling in an acidic pH medium through the formation of a complex hydrogen‐bonded structure and maximal swelling due to the electrostatic repulsion due to the ionization of the carboxylic groups in pH 7.4 medium. The degradation in vitro shows that the degree of degradation (R%) depended on the concentration of cross‐linking agent and content of GG. The hydrogel shows a minimum release of 5‐ASA due to the complex hydrogen bonded structure of the hydrogels in the medium of pH 2.2. The enzymatic degradation of hydrogels by cecal bacteria can accelerate the release of 5‐ASA entrapped in the hydrogel in pH 7.4 medium. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis and characterization of PVP/AAc copolymer hydrogel and its applications in the removal of heavy metals from aqueous solution

Chelating poly(vinylpyrrolidone/acrylic acid) (PVP/AAc) copolymer hydrogels were prepared by radiation-induced copolymerization. The effects of preparation parameters such as PVP content in the hydrogel and irradiation dose on the swelling behavior of the hydrogel were studied. The pH dependent swelling was investigated. The thermal stability of the prepared hydrogel and the metal chelated ones was characterized by TGA. The removal of Fe(III), Cu(II), and Mn(II) from aqueous solution by the prepared PVP/AAc chelating hydrogel was examined by batch equilibration technique. The influence of treatment time, pH, and the initial feed concentration on the amount of the metal ions removed was studied. The results show that the removal of the metal ion followed the following order: Fe(III) > Cu(II) > Mn(II). The amounts of the removed metal ions increased with treatment time and pH of the medium. To re-use the hydrogel, the metal ions were stripped by using 2 N HCl.     

Preparation and release profiles of pH/temperature-responsive carboxymethyl chitosan/P(2-(dimethylamino) ethyl methacrylate) semi-IPN amphoteric hydrogel

Thermo- and pH-responsive semi-IPN polyampholyte hydrogels were prepared by using carboxymethyl chitosan and P(2-(dimethylamino) ethyl methacrylate) with N N'-Methylenebisacrylamide (BIS) as crosslinking agent. It was found that the semi-IPN hydrogel shrunk most at the isoelectric point (IEP) and swelled when pH deviated from the IEP. Its swelling ratio dramatically decreased between 30 and 50 °C at pH 6.8 buffer solution. It also showed good reversibility. The UV results showed that when the pH values of drug release medium were 3.7, 6.8, and 9 at 25 °C, the cumulative release rates reached 83.1, 51.5, and 72.2%, respectively. The release rate of coenzyme A (CoA) was higher at 50 °C than 37 and 25 °C at pH 6.8 solution. The release rate decreased with increasing the content of carboxymethyl chitosan at 25 °C in pH 6.8 solution. The results showed that semi-IPN hydrogel seems to be of great promise in pH/temperature drug delivery systems.     

Preparation of Crosslinked Chitosan/Silk Fibroin Blend Films for Drug Delivery System

Crosslinked chitosan/silk fibroin blend films were prepared by a solution casting technique using glutaraldehyde as crosslinking agent. Drug release characteristics of the blend films with various blend compositions were investigated. Theophylline, diclofenac sodium, amoxicillin trihydrate, and salicylic acid were used as model drugs. The release studies were performed at 37 °C in buffer solutions at pH 2.0, 5.5, and 7.2. It was found that the blend films with 80% chitosan content showed the maximum amount of model drug release at pH 2.0 for all the drugs studied here. This result corresponded to the swelling ability of the blend films. From a swelling study, the maximum degrees of swelling of the drug‐loaded blend films were obtained at this pH and blend composition. The amount of drugs released from the films with 80% chitosan content, from the highest to the lowest values, occurred in the following sequence: salicylic acid > theophylline > diclofenac sodium > amoxicillin.

Comparison of the amounts of drug released from chitosan and the blend film with 80% chitosan content at pH 2.0: (filled) chitosan film, and (blank) blend film with 80% chitosan content (SAL = salicylic acid, THEO = theophylline, DFS = diclofenac sodium, AMX = amoxicillin).     

Preparation and Characterization of Poly(N‐Vinylpyrrolidone‐co‐Methacrylic Acid) Hydrogels

In this study, N‐vinylpyrrolidone (VP)/methacrylic acid (MAA) copolymers have been prepared at three different mole percents, the methacrylic acid composition being around 5, 10, 15%. MAA and VP monomer mixtures have been irradiated in ⁶⁰Co‐γ source at different irradiation doses and percent conversions have been determined gravimetrically. ～80% conversion of monomers into hydrogels were performed at 3.4 kGy irradiation dose. These hydrogels were swollen in distilled water at pH 4.0, 7.0, and 9.0. P(VP/MAA) hydrogel which contains 5% methacrylic acid showed the maximum % swelling at pH 9.0 in water. Diffusion of water was found to be of non‐Fickian character. Diffusion coefficients of water in P(VP/MAA) hydrogels were calculated. Initial swelling rates of P(VP/MAA) hydrogels increased with increasing pH and MAA content in hydrogels. Swelling kinetics of P(VP/MAA) hydrogels was found to be of second order. Thermal behavior of PMAA, PVP and P(VP/MAA) hydrogel were investigated by thermal analysis. P(VP/MAA) hydrogel gained new thermal properties and the temperature for maximum weight loss and temperature for half‐life of P(VP/MAA) hydrogel were determined.     

Synthesis of Carboxymethyl Cellulose Based Drug Carrier Hydrogel Using Ionizing Radiation for Possible Use as Site Specific Delivery System

A unique natural polymer based colon specific drug carrier was prepared from carboxymethyl cellulose (CMC) and acrylic acid (AAc) in aqueous solution employing γ‐radiation induced copolymerization and crosslinking. The effect of preparation conditions such as the natural polymer content and irradiation dose on gelation process was investigated. The swelling behavior of the prepared hydrogels was characterized by investigating the time and pH dependent swelling of the (CMC/AAc) hydrogels of different CMC content. The effects of the hydrogel composition and pH of the swelling medium on the swelling indices were estimated. The results show that the increment in the CMC content in the feed solution enhances the gelation process. The results also show the dependence of the swelling indices on both hydrogel composition and pH value of the swelling medium. To evaluate the ability of the prepared hydrogel to be used as a colon‐specific drug carrier, the release profile of theophylline was studied as a function of time at pH 1 and pH 7.     

壳聚糖-丝心蛋白合金膜的研究(Ⅱ)──半互穿聚合物网络型膜对pH和离子的敏感性

研究了壳聚糖-丝心蛋白半互穿聚合物网络型膜对pH值和离子的敏感性,发现该膜在pH<3.3时溶胀度剧烈增加;在pH=2时,是否出现溶胀极大值与膜组分的含量及交联剂的含量有关;膜在不同pH值溶液中可交替溶胀和收缩,且这种溶胀-收缩行为重复可逆。同时,该膜在不同离子溶液中的溶胀度亦不同;在相同离子强度的溶液中,此膜在3价离子中的溶胀度最大。