明胶/聚(N-异丙基丙烯酰胺)水凝胶的制备及其在药物控释中的应用

以马来酸酐改性后的明胶(N-马来酰化明胶)(明胶-g-MA)为交联剂与N-异丙基丙烯酰胺共聚制备了一系列水凝胶。研究了交联剂用量对水凝胶溶胀性的影响,结果表明交联剂用量为45%(质量分数)时水凝胶具有最高的溶胀率,水凝胶的平衡溶胀率随温度升高逐渐降低,温敏性随缓冲液中NaCl浓度增加逐渐增强。包埋在水凝胶样品内的牛血清蛋白(BSA)具有良好的缓释效果,其累积释放率随交联剂用量增加而降低,高于相变温度时释放速度加快。     

超大孔水凝胶P(AA-co-DMAA)的制备及释放性能

以丙烯酸(AA)和N,N-二甲基丙烯酰胺(DMAA)为单体,采用泡沫分散聚合法制备P(AA-co-DMAA)超大孔水凝胶及载有盐酸小檗碱的载药凝胶,研究单体配比、温度、pH值和NaCl浓度对载药凝胶释放性能的影响。结果表明,凝胶具有超大孔结构及pH敏感性;n(AA)∶n(DMAA)=1∶1的载药凝胶释放率最小;升高温度使载药凝胶的释放率增大;在pH=1的HCl溶液和pH=6.8的磷酸盐缓冲溶液中,载药凝胶释放率远大于蒸馏水;NaCl溶液浓度越大,载药凝胶的释放率越大。     

形状记忆型水凝胶的制备及其在药物控制释放中的应用

以戊二醛为交联剂,制备了pH敏感性明胶-果胶水凝胶(GT-PT)和明胶-辛基果胶水凝胶(GT-OPT),研究了交联剂用量、温度、pH值对凝胶溶胀性能的影响及溶胀-消溶胀性能。结果表明,当温度在30～60℃时,凝胶的溶胀率随温度的升高而增大;且具有明显的pH敏感性,碱性条件下的溶胀率大于酸性条件下的溶胀率;不同pH值条件下,明胶-果胶水凝胶具有"形状记忆"功能。包埋在水凝胶中的牛血清蛋白在pH=1.0时的释药率大于pH=7.8和pH=9.18时的释药率。此类水凝胶有望用于蛋白质的pH值及温度控制释放。     

前端聚合法制备聚(N-乙烯基己内酰胺-co-N,N-二甲基丙烯酰胺)智能水凝胶

本工作采用前端聚合法制备聚(N-乙烯基己内酰胺-co-N,N-二甲基丙烯酰胺)智能水凝胶,针对两种单体,即N-乙烯基己内酰胺( N-VCL)和N, N-二甲基丙烯酰胺(DMAA),研究了单体物质的量比、交联剂和引发剂用量对前端聚合参数以及共聚水凝胶性能的影响,并用阿司匹林作为模型药物,评价了共聚物水凝胶对阿司匹林的负载和缓释效果.实验表明,共聚产物具有温度敏感性,相转变温度在25～40 ℃之间,单体N,N-二甲基丙烯酰胺(DMAA)加入之后,凝胶对温度刺激的敏感性响应更为明显.随单体DMAA含量的增加,波温、波速也升高,温室溶胀率增加.当n(N-VCL) ∶ n(DMAA)=5 ∶5时,水凝胶的温敏性最好;随交联剂用量的增大,共聚凝胶室温溶胀能力、温敏性均有所降低;随引发剂用量的增加,相变温度升高.随单体DMAA比例增加,在25 ℃和37 ℃两种温度下凝胶载药量均增加,但就释药效果而言,在37 ℃下凝胶释药效率更高,总释药率也更高.     

羟化聚天冬氨酸水凝胶的制备及药物缓释性能

以L天冬氨酸为单体进行缩聚反应所得到的高分子量聚琥珀酰亚胺(PSI)为母体,己二胺为交联荆,采用乙醇胺对其进行改性,制备了羟化聚天冬氨酸水凝胶.研究了反应温度、交联剂及乙醇胺用量对水凝胶溶胀性能的影响;以水杨酸为模型药物,研究了其载药性能及在不同释放介质中的释放行为.结果表明,反应温度为40℃,交联剂用量为PSI用量的...     

含笼形POSS的PNIPAM温敏性水凝胶的溶胀及药物缓释行为

以八乙烯基低聚倍半硅氧烷(OVPS)为交联剂,通过溶液共聚制备了聚N-异丙基丙烯酰胺有机/无机杂化水凝胶(P(OVPS-co-NIPAM)),研究了其溶胀、消溶胀和再溶胀及药物缓释行为。结果表明,所有P(OVPS-co-NIPAM)杂化水凝胶的平衡溶胀率SR均随温度升高而降低。20℃,5-P(OVPS-co-NIPAM)杂化水凝胶在去离子水中的SR与常规水凝胶P(MBA-co-NIPAM)相同,但在生理盐水中的SR,前者明显大于后者。随着OVPS含量的增加,杂化水凝胶的SR、再溶胀和消溶胀速率均逐渐下降。5-P(OVPS-co-NIPAM)杂化水凝胶的载药率和累积释药率均高于常规水凝胶P(MBA-co-NIPAM)。此外,P(OVPS-co-NIPAM)杂化水凝胶的药物释放速率均高于常规水凝胶,而且20℃时随OVPS含量增加,释药加快。     

壳聚糖透明质酸复合水凝胶的制备及性能

用零长度的1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC·HCl)和N-羟基丁二酰亚胺(NHS)作为偶联剂和稳定剂制备了壳聚糖基透明质酸复合水凝胶,探讨了溶液pH值对该类水凝胶溶胀性的影响。溶液的pH在4.0时,该类水凝胶的溶胀率最低,升高和降低溶液的pH,该类水凝胶的溶胀率均升高,文中还对水凝胶的降解率进行了研究,实验发现,交联后的水凝胶具有一定的稳定性。包埋在此水凝胶中的牛血清蛋白(BSA)释放随载药介质pH值的变化而显著不同,pH 7.4条件下载药的水凝胶释药率大于pH 1.2条件下的释药率。因此,具有pH敏感性的壳聚糖透明质酸复合水凝胶在药物运输领域具有潜在的应用。     

注射型壳聚糖温敏相变复合材料的制备及性能研究

制备了一种注射型壳聚糖(CS)温敏相变复合材料,首先采用乳化-化学交联法,以戊二醛为交联剂,制备包载甲氨蝶呤(MTX)的壳聚糖微球,然后采用离子交联法,向CS溶液中滴加50%甘油磷酸钠溶液,制备CS温敏水凝胶。将CS载药微球分散于水凝胶中,制得温敏相变复合材料。结果表明,所制得的微球载药量为12.98%,包封率为32.66%,且粒径均一,分散性良好,具有良好的通针性;水凝胶在37℃下1min内可发生相变,由溶胶转变为凝胶,具有良好的温度敏感性;制备的温敏相变复合材料具有良好的原位注射性,且4h内药物释放率为35.65%,缓释效果明显。     

可降解聚天冬氨酸水凝胶的制备与应用研究

以天冬氨酸为原料,合成了聚丁二酰亚胺(PSI);采用氨基封端的聚乙二醇作为交联剂制备出了聚天冬酰胺水凝胶;研究了聚丁二酰亚胺分子量、交联剂分子量以及交联剂的用量等因素对水凝胶溶胀性能的影响,并研究了以甲硝唑为模型药物,在37℃下、pH=4.6的介质中,药物在聚天冬酰胺水凝胶中的控制释放.     

pH敏感型黄原胶/聚乙烯醇水凝胶的制备与表征

通过化学交联结合物理交联的方法制备了一种pH敏感型的黄原胶/聚乙烯醇(XG/PVA)复合水凝胶,研究了XG与PVA不同质量比、不同交联剂用量及不同冷冻-解冻循环次数对XG/PVA水凝胶溶胀性能和力学性能的影响。结果表明,XG与PVA质量比为1∶5,交联剂环氧氯丙烷用量为5%,冷冻-解冻循环3次时,XG/PVA复合水凝胶内部结构均匀紧密且具有较高的溶胀性能,此时凝胶的弹性模量和压缩强度达到(26.30±0.03)kPa和(134.36±0.43)kPa。并探讨了该实验条件制备的XG/PVA水凝胶的pH敏感性及pH刺激响应性,并以牛血清蛋白(BSA)为模型进行了体外药物释放性能测试及材料生物相容性实验的研究。结果表明,该凝胶具有良好的pH敏感性及pH刺激响应特性,不同pH环境下可实现体外BSA的控制释放,且具有良好的生物相容性,有望用于药物控释载体。     

Synthesis and characterization of a pH/temperature responsive glycine-mediated hydrogel for drug release

In this work, a pH/temperature responsive hydrogel (PMEA) from N-acryloylglycine methyl ester (NAGME), N-acryloylglycine ethyl ester (NAGEE), and acrylic acid (AAc) was synthesized by free radical polymerization. The swelling behaviors and drug release properties of hydrogels were systematically investigated at different temperature, pH, and AAc content. It was found that the hydrogel PMEA demonstrated pH and temperature responsive nature. The caffeine-release behaviors showed that only 49.1% caffeine was released from PMEA in pH 2.70 phosphate buffer solution (PBS) after 500 minutes, whereas more than 93.9% caffeine was gradually diffused into the medium in pH 7.49 PBS over the same time interval. In addition, the caffeine release was much higher at 37°C than that at 14°C in deionized water. As seen from the results, the PMEA seems to be a potential drug carrier with pH-temperature responsiveness.     

PNIPAAm/CMC半互穿网络水凝胶的合成及性质

以N-马来酰化壳聚糖为交联剂,N-异丙基丙烯酰胺(NIPAAm)为单体,羧甲基纤维素钠(CMC)为半互穿材料,在水溶液中通过自由基聚合制备了PNIPAAm/CMC半互穿网络水凝胶.所合成的水凝胶的低临界溶解温度(LCST)在33℃左右,CMC的加入对水凝胶的LCST无显著影响,但随着CMC用量的增加,水凝胶的温度敏感性...     

Synthesis and characterization of a pH/temperature responsive glycine-mediated hydrogel for drug release

In this work, a pH/temperature responsive hydrogel (PMEA) from N-acryloylglycine methyl ester (NAGME), N-acryloylglycine ethyl ester (NAGEE), and acrylic acid (AAc) was synthesized by free radical polymerization. The swelling behaviors and drug release properties of hydrogels were systematically investigated at different temperature, pH, and AAc content. It was found that the hydrogel PMEA demonstrated pH and temperature responsive nature. The caffeine-release behaviors showed that only 49.1% caffeine was released from PMEA in pH 2.70 phosphate buffer solution (PBS) after 500 minutes, whereas more than 93.9% caffeine was gradually diffused into the medium in pH 7.49 PBS over the same time interval. In addition, the caffeine release was much higher at 37°C than that at 14°C in deionized water. As seen from the results, the PMEA seems to be a potential drug carrier with pH-temperature responsiveness.     

Biodegradation of hydrophilic–hydrophobic hydrogels and its effect on albumin release

The objective of this study was to examine the effects of composition ratio of a new class of bicomponent biodegradable hydrogels and the molecular weights of the constituents on the hydrolytic degradability of the hydrogels and their release of bovine serum albumin (BSA). Biodegradable hydrogels were prepared from dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of dex-AI to PDLLAM composition ratio. The results obtained indicated that the hydrolytic degradation of these biodegradable hydrogels could be controlled by adjusting the composition ratio of dex-AI to PDLLAM or by changing their molecular weights. Along with the hydrogel degradation, water content of the hydrogels changed, and 3D porous network structure was observed. Generally, as the PDLLAM composition in the hydrogels increased, the rate of weight loss increased due to the hydrolytic degradation of the PDLLAM. The increase in molecular weights of either dex-AI or PDLLAM would decrease the degradation rate of the dex-AI/PDLLAM hydrogels. BSA release data correlated well with the hydrogel degradation profiles, suggesting that the extent and rate of BSA release would be mainly controled by hydrogel degradation. As the PDLLAM composition in the hydrogel increased, the extent and rate of BSA release also increased. An increase in the molecular weights of the hydrogel constituents, however, led to a decrease in BSA release.     

丝胶/Poly(NIPAm-LMSH)纳米复合凝胶的层状形态和溶胀行为

采用半互穿网络技术和原位自由基聚合将生物相容性和吸水性优良的丝胶蛋白（SS）引入聚异丙基丙烯酰胺-硅酸镁锂（Poly（NIPAm-LMSH））纳米复合凝胶网络,制得高溶胀度和快速响应的SS/Poly（NIPAm-LMSH）纳米复合凝胶,研究了丝胶含量对纳米复合凝胶的孔洞形态、溶胀动力学、结晶结构、相容性和稳定性的影响。结果表明：冷冻干燥后的SS/Poly（NIPAm-LMSH）水凝胶呈多孔结构,孔洞尺寸为20~30 μm,孔壁薄,为1~4 μm,且随丝胶含量增加而由多面体结构变为狭长形的层状结构。相比于溶胀平衡的纯纳米复合凝胶,丝胶的引入显著提高了其溶胀度,溶胀初期属于Non-Fickian扩散,37 ℃ 10 min内即可失去90%的水。丝胶在凝胶中具有良好的相容性,SS/Poly（NIPAm-LMSH）纳米复合凝胶的 T_g为141~144 ℃,最大热分解温度为365~373 ℃,质量残留率随丝胶含量的增加而增大。     

物理/化学复合交联剂配比对凝胶温敏性的影响

采用化学交联剂亚甲基双丙烯酰胺(MBA)和物理交联剂无机纳米黏土硅酸镁锂(LMSH)复配制备聚异丙基丙烯酰胺(PNIPAM)水凝胶。随m(MBA)∶m(LMSH)的质量比由9∶1降至为1∶9,水凝胶的透光度和溶胀度增加。凝胶的内部形态取决于交联剂配比,孔洞尺寸随LMSH含量增加而增加。当m(MBA)∶m(LMSH)的质量比为9∶1和1∶9时,温度脉冲响应性最好,但m(MBA)∶m(LMSH)的质量比为1∶9时凝胶对温度的响应最为敏感,20℃下的储能模量最高。DSC结果表明体积相转变温度(VPTT)均在33℃左右,但VPTT范围随LMSH含量增加而窄化。     

可生物降解聚乳酸/纳米纤维素复合材料的亲水性和降解性

采用溶液浇铸法制备可生物降解聚乳酸(PLA)/纳米纤维素复合材料。测试了该复合材料的吸水性,在37℃的磷酸缓冲溶液中及在土壤中的降解性。并用扫描电子显微镜(SEM)观察了降解前后复合材料的表面形貌。结果表明,随着复合材料中纳米纤维素质量分数的增加,复合材料的吸水性和降解性均随之提高,明显优于纯的聚乳酸。从SEM的图片中看出,降解后,在磷酸缓冲溶液中的复合材料表面有孔洞,而在土壤中的则有明显被侵蚀的痕迹。     

Synthesis and characterization of matrix metalloprotease sensitive-low molecular weight hyaluronic acid based hydrogels

Hyaluronic acid is a naturally derived glycosaminoglycan (GAG) involved in biological processes. A low molecular weight hyaluronic acid (50 kDa)-based hydrogel was synthesized using acrylated hyaluronic acid. Matrix metalloproteinase (MMP) sensitive hyaluronic acid-based hydrogels were prepared by conjugation with two different peptides: cell adhesion peptides containing integrin binding domains (Arg-Gly-Asp: RGD) and a cross-linker with MMP degradable peptides to mimic the remodeling characteristics of natural extracellular matrices (ECMs) by cell-derived MMPs. Mechanical properties of these hydrogels were evaluated with different molecular weights of acrylated hyaluronic acid (10 kDa and 50 kDa) cross-linked by MMP sensitive peptides by measuring elastic modulus, viscous modulus, swelling ratio and degradation rate. The MMP sensitive hydrogel based on the 50 kDa hyaluronic acid showed a 31.5-fold shorter gelation time, 4.7-fold higher storage modulus and 0.51-fold smaller swelling ratio than those of the hydrogel based on the 10 kDa. Degradation rate was dependent on MMP sensitivity of the peptide cross-linker. MMP sensitive hyaluronic acid based hydrogels were degraded faster than MMP insensitive-hyaluronic acid-based hydrogels. Human mesenchymal stem cells (MSCs) were cultured in MMP-sensitive or insensitive hyaluronic acid-based hydrogels (50 kDa hyaluronic acid) and/or immobilized cell adhesive RGD peptides. Cells cultured in the MMP-sensitive hydrogel with RGD peptides showed dramatic cell spreading compared with that of the control, which remained round. This MMP-sensitive low molecular weight hyaluronic acid-based hydrogel could be useful in tissue engineering by improving tissue defect regeneration and tissue remodeling.     

壳聚糖/聚(N-异丙基丙烯酰胺)全互穿网络水凝胶的制备及性能

以壳聚糖(CS)和N-异丙基丙烯酰胺(NIPAAm)为原料,N,N'-亚甲基双丙烯酰胺(BIS)为交联剂,制备具有温度和pH值双敏感性的全互穿网络水凝胶(Full-IPN);利用红外光谱(FT-IR)对其分子结构进行表征,扫描电镜(SEM)观察其内部形貌,并通过DSC对其低临界溶解温度(LCST)进行表征,最后研究了不...