壳聚糖基复合水凝胶在创伤修复中的应用

综述了近年来壳聚糖与温敏材料、生长因子、多肽及多种其他材料通过物理或化学方法复合制备的壳聚糖基水凝胶及其在创伤修复领域中研究和应用的新进展,并对其发展前景进行了展望,期望为后续壳聚糖基水凝胶的进一步研究提供参考。     

壳聚糖基复合水凝胶在创伤修复中的应用

综述了近年来壳聚糖与温敏材料、生长因子、多肽及多种其他材料通过物理或化学方法复合制备的壳聚糖基水凝胶及其在创伤修复领域中研究和应用的新进展,并对其发展前景进行了展望,期望为后续壳聚糖基水凝胶的进一步研究提供参考。     

壳聚糖基可注射温敏凝胶的制备及其药物缓释性能研究

研究不同浓度的壳聚糖、不同质量配比的α-甘油磷酸钠和β-甘油磷酸钠混合盐和混合溶液的pH等因素对CS/GP溶液凝胶化性能的影响,在37℃形成凝胶体系负载模型药物依诺沙星考察该凝胶的释药性能。结果表明:壳聚糖浓度为100 mg,α-甘油磷酸钠和β-甘油磷酸钠按质量比为1∶4混合,控制凝胶体系pH为7.2,凝胶体系IGT可由45℃降至32℃;37℃下,可在3.5 min快速凝胶,凝胶强度达到约0.48 kPa。以依诺沙星为模型药物,载药凝胶体系可持续释放药物10 d左右,有很好的药物缓释作用。     

壳聚糖基可注射温敏互穿水凝胶制备及表征

以β-甘油磷酸钠(GP)为羟丙基壳聚糖(HPCS)或壳聚糖季铵盐(HTCC)的温敏交联剂、氯化钙(CaCl_2)为海藻酸钠(SA)的螯合交联剂,采用共混工艺,制备以壳聚糖衍生物-GP为第1网络、海藻酸钙为第2网络的可注射温敏互穿水凝胶。利用高斯软件基于氢键理论探讨凝胶温敏相变机理。利用红外光谱仪、扫描电子显微镜、热重分析仪和流变分析仪对凝胶性能进行了表征。当ρ_(HPCS)=18.75 mg/mL,ρ_(GP)=75 mg/mL,ρ_(SA)=18.33 mg/mL和ρ(CaCl_2)=1.67 mg/mL时,凝胶在37℃温敏凝胶化时间为(85±15)s,压缩弹性模量为(54±15)kPa,损耗模量G″和储能模量G′比值为0.10±0.025。由此可知,HPCS-GP/Ca-Alg复合凝胶可在生理温度环境凝胶化且时间可控,凝胶机械强度良好,在组织工程领域中具有应用潜力。     

光交联对HDPE凝胶量的影响

用安息香二甲醚和三(丙烯酰氧乙基)异氰尿酸酯(TAEIC)作为PE的光敏剂和助交联剂,研究了它们的用量、光照时间、交联温度,紫外光光强对PE交联度的影响。结果表明,安息香二甲醚是一种有效的光敏剂,引发效率较高;助交联剂可以提高交联效率;光照时间、紫外光光强和交联温度等对PE的交联度均有明显的影响。     

壳聚糖水凝胶溶胀性能的研究

壳聚糖水凝胶在pH7.0,0.2%甘氨酸缓冲溶液中的最高溶胀比R为637.5,溶胀体积比Rv为12.75;当pH≤7.0时,表现强的吸水性;pH>8.5时脱水收缩;在<1%NaCl溶液中,表现出不同程度的吸胀性;在≥1%NaCl溶液中,无吸胀性,随着环境温度的升高,吸胀性下降;甲醇作为成胶介质,凝胶的吸胀性最强;交链度与壳聚糖水凝胶的Rv成反比。因此认为,壳聚糖水凝胶在农业、医药、化工和生物学的应用及研究中将表现重要作用。     

壳聚糖接枝聚丙烯酰胺水凝胶的制备及性质研究

通过接枝共聚反应制备了几种壳聚糖接枝聚丙烯酰胺水凝胶，其中过硫酸钾为自由基引发剂，亚甲基双丙烯酰胺或甲醛为交联剂，并研究了实验因素，如交联剂浓度和单体比率对水凝胶溶胀能力的影响。实验表明水凝胶具有离子强度、pH值和温度敏感性。这种可随外界因素响应及“开关”的性质，使此类智能水凝胶有望成为生物制品载体，例如药物载体。     

交联剂结构对可生物降解壳聚糖水凝胶性能影响的研究

通过NaIO₄氧化制备不同的醛基多糖,结果表明,在同一氧化条件下制备的氧化多糖醛基含量不同。以醛基多糖和羧甲基壳聚糖(CMCS)为原料通过席夫碱反应制备了一系列多糖水凝胶。结果表明,不同醛基多糖交联的CMCS水凝胶在结构性能上具有较大的差异性,包括：孔径、吸水性和力学强度。细胞毒性测试表明,不同结构的多糖水凝胶均具有较好的细胞相容性。该研究有望依据水凝胶应用的目标性能合理地定制多糖水凝胶的制备方案,为多糖水凝胶进一步的功能改性及在伤口敷料、细胞支架等生物医学领域的应用奠定基础。     

壳聚糖纤维/壳聚糖/海藻酸钠水凝胶溶胀性能与抑菌性能

制备了壳聚糖(CS)/海藻酸钠(SA)复合水凝胶,并通过加入吸水性壳聚糖长纤维、45%壳聚糖水刺无纺布、80%壳聚糖水刺无纺布、100%壳聚糖水刺无纺布、100%壳聚糖针刺无纺布这五种纤维,增强复合水凝胶的力学性能,探究了复合水凝胶的吸水溶胀性能与抑菌性能。结果表明,加入纤维后水凝胶在蒸馏水中的溶胀比明显降低,在碱性环境中,水凝胶的溶胀比显著上升,在偏中性环境中,水凝胶的溶胀比最低;加入纤维后,复合水凝胶仍具有一定的抑菌性,无纤维添加的水凝胶呈现出的抑菌能力一般,而加入了吸水性壳聚糖长纤维的具有最佳的抑菌性能。     

谷氨酸/N-琥珀酰化壳聚糖水凝胶的制备和性能

以琥珀酸酐、壳聚糖为原料制备水溶性的N-琥珀酰化壳聚糖(NSC),再以谷氨酸(GA)为交联剂,在室温条件下,一定质量的GA和NSC在水溶液中通过自组装制备了GA/NSC水凝胶,研究了GA/NSC水凝胶的稳定性和溶胀性能,运用红外光谱(IR)、差示扫描量热仪(DSC)、扫描电子镜(SEM)等对其结构进行了表征,并考察了GA/NSC水凝胶的细胞毒性。结果表明,GA/NSC水凝胶为pH响应的离子交联水凝胶,具有较好的溶胀性能及生物相容性。     

壳聚糖/聚醚半互穿网络水凝胶的性能

以壳聚糖和聚醚为原料,戊二醛为交联剂,在醋酸溶液中制备了壳聚糖/聚醚水凝胶,反应温度45℃,聚醚和壳聚糖的质量比为0.4,戊二醛浓度为0.053 mol/L,壳聚糖黏均相对分子质量为24.86×104时,其凝胶饱和溶胀度为876.25%;反应温度45℃,聚醚和壳聚糖的质量比为0.6,戊二醛浓度为0.267 mol/L,壳聚糖黏均相对分子质量为24.86×104时,其凝胶硬度为151.896 kPa。     

Studies on Glutaraldehyde Crosslinked Chitosan Hydrogel Properties for Drug Delivery Systems

Chitosan was crosslinked with different amount of glutaraldehyde to prepare appropriate hydrogels to be used as drug delivery system. The swelling behavior of freeze-dried hydrogels in aqueous media at different temperature and pHs has been examined. The swelling, porosity and biocompatibility behavior of samples were investigated to check effects of polymer/polymer and polymer/drug interactions on these system characteristics. Obtained experimental results illustrates that with increasing crosslinking agent from 0.068 to 0.30, swelling of the prepared samples degrees from 1200% to 600% and pore diameters change from 100 to 500 µm. To investigate systems biocompatibility in gastric conditions, effects of crosslinker concentration on the pepsin enzyme activity have been studied using variation of relative viscosity of the system. Presented results also show that with increasing crosslinker agent concentration activity of enzyme reduces considerably and so crosslinker molar ratio to amine functional groups of chitosan must be less than 0.2.     

混合酸制备壳聚糖温敏水凝胶的研究

提出了以醋酸-盐酸混合液为溶剂,制备壳聚糖-αβ甘油磷酸钠水凝胶。探讨了它们对壳聚糖水凝胶性能的影响,并从分子间相互作用力的角度对各种现象进行了理论解释。实验结果表明:采用混合酸为溶剂,能够简单地对凝胶的粘度和凝胶化时间进行控制,并且pH对这种体系影响较小。     

N-琥珀酰壳聚糖/氧化硫酸软骨素水凝胶的制备

采用N-琥珀酰壳聚糖(NCS)与氧化硫酸软骨素(OCS)进行复合,制备NCS/OCS复合水凝胶.考察了OCS与NCS不同质量比对复合水凝胶的凝胶化时间、压缩强度、平衡溶胀以及体外降解等物理化学性能的影响.结果表明:当m(NCS):m(OCS)为7:3时复合水凝胶能满足临床要求,此时复合水凝胶在37 ℃条件下的凝胶时间约为16 min,压缩强度为(5.82±0.5) kPa,30d后,复合水凝胶的剩余质量分数约为40％.通过氧化硫酸软骨素与N-琥珀酰壳聚糖进行复合,可注射水凝胶的凝胶强度和降解性能得到明显改善,该材料有望在软骨组织工程支架方面得到应用.     

Preparation and Swelling Study of a pH-Dependent Interpolymeric Hydrogel Based on Chitosan for Controlled Drug Release

Novel pH-dependent, biodegradable interpolymeric network (IPN) hydrogels were prepared for controlled drug release investigations. The IPN hydrogels were prepared by irradiation of solutions of N-acryloyglycine (NAGly), polyethylene glycol diacrylate (PEGDA) mixed with chitosan, in the presence of a lower amount of glutaraldehyde as the crosslinker and using 2,2-dimethoxy-2-phenyl acetophenone as the photo-initiator. The equilibrium swelling studies were carried out for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 (simulated gastric and intestinal fluids, respectively). 5-Fluorouracil (5-FU) was entrapped, as a model therapeutic agent, in the hydrogels and equilibrium-swelling studies were carried out for the drug-entrapped gels at 37°C. The in-vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4.     

Optimization and Evaluation of a Chitosan/Hydroxypropyl Methylcellulose Hydrogel Containing Toluidine Blue O for Antimicrobial Photodynamic Inactivation

Photodynamic inactivation (PDI) combined with chitosan has been shown as a promising antimicrobial approach. The purpose of this study was to develop a chitosan hydrogel containing hydroxypropyl methylcellulose (HPMC), chitosan and toluidine blue O (TBO) to improve the bactericidal efficacy for topical application in clinics. The PDI efficacy of hydrogel was examined in vitro against the biofilms of Staphylococcusaureus (S. aureus) and Pseudomonasaeruginosa (P. aeruginosa). Confocal scanning laser microscopy (CSLM) was performed to investigate the penetration level of TBO into viable S. aureus biofilms. Incorporation of HMPC could increase the physicochemical properties of chitosan hydrogel including the hardness, viscosity as well as bioadhesion; however, higher HMPC concentration also resulted in reduced antimicrobial effect. CSLM analysis further demonstrated that higher HPMC concentration constrained TBO diffusion into the biofilm. The incubation of biofilm and hydrogel was further performed at an angle of 90 degrees. After light irradiation, compared to the mixture of TBO and chitosan, the hydrogel treated sample showed increased PDI efficacy indicated that incorporation of HPMC did improve antimicrobial effect. Finally, the bactericidal efficacy could be significantly augmented by prolonged retention of hydrogel in the biofilm as well as in the animal model of rat skin burn wounds after light irradiation.     

壳聚糖的表面性能及分子量与脱乙酰度的影响

应用红外光谱法对四种壳聚糖样品进行了结构表征,同时估算了其脱乙酰度,并用粘度法测定了分子量。根据Washburn的浸渍理论和van Oss-Chaudhury-Good的组合理论,应用柱状灯芯技术,对壳聚糖的表面性能进行了测试。研究发现,壳聚糖的分子量和脱乙酰度都影响其表面性能。当脱乙酰度相同时,分子量与表面能γS及表面能分量γSLW、酸碱比值γS+/γS-成正比,而与其酸性力γS+和碱性力γS-以及极性率γAB/γs成反比;而分子量相近时,表面性能可能主要受脱乙酰度的影响。随着脱乙酰度的增加,壳聚糖的表面能γS及其分量γSLW、酸碱比值γS+/γS-都增大。实验所测得的壳聚糖的表面能数据得到文献的支持。     

温度及pH敏感性聚乙烯醇/羧甲基壳聚糖水凝胶的制备与性能研究

以聚乙烯醇(PVA)和羧甲基壳聚糖(CMCh)为原料,采用60Co-γ射线辐照交联制备聚乙烯醇/羧甲基壳聚糖(PVA/CMCh)水凝胶;研究了PVA与CMCh的配比、温度、pH及离子强度等对PVA/CMCh水凝胶溶胀率的影响。结果表明适当配比的PVA/CMCh水凝胶具有一定的温度、pH及离子敏感性。该水凝胶在5~20°C时具有较高的溶胀率,温度在20°C以上溶胀率较低,并且有一定的可逆性;水凝胶在pH较低(pH<4.0)和较高(pH>6.0)时溶胀率均较大,而当pH为4.0~6.0时溶胀率较小,显示出一定的pH敏感性。     

Fabrication and Properties of Gelatin/Chitosan Composite Hydrogel

Gelatin/chitosan hydrogels were prepared by using glutaraldehyde as crosslinker. The porous structure was confirmed by scanning electron microscope (SEM). Swelling ratios of the hydrogels with various ratio of gelatin to chitosan and crosslinker reagent dosage were studied in phosphate-buffered saline (PBS). In addition, in-vitro cytotoxicity was assessed via MTT assay with fibroblastic cell cultured in hydrogel extractions. It was found that by increasing glutaraldehyde dosage and chitosan content, the swelling ratio of the hydrogels decreased in buffer solutions. The MTT test showed that the gelatin/chitosan hydrogel clearly presented adequate cell viability, non-toxicity, and suitable properties. Therefore, these developed blends, based on gelatin and chitosan has broadened the number of choices of biomaterials to be potentially used in biomedical applications such as biomaterial, drug delivery vehicles and skin tissue engineering.     

聚(异丙基丙烯酰胺-羟甲基丙烯酰胺)/壳聚糖水凝胶的制备及其释药性能

以异丙基丙烯酰胺(NIPAAm)和羟甲基丙烯酰胺(NHMAm)为共聚单体与壳聚糖(CS)制备形成了温度敏感和pH敏感的互穿网络(IPN)水凝胶Poly(NIPAAm-co-NHMAm)/CS;用红外光谱表征了其结构特征,研究了不同条件下水凝胶的溶胀性能,并初步研究了水凝胶对药物双氯芬酸钠(DS)的缓释效果。结果表明,该水凝胶具有明显的温度和pH敏感性,温度越高,溶胀度越小,释药越慢;pH越小,溶胀度越大;CS含量为0.6%时溶胀度最大。在NHMAm单体质量配比为8.7%时,水凝胶的低临界溶液温度(LCST)达到38℃,且此时对DS持续释药时间可达到24 h。水凝胶的释药动力学曲线符合修正的一级动力学模型。该水凝胶体系可通过改变NHMAm单体配比来调节温敏特性,是一种潜在的温度和pH双重敏感的药物缓释载体。