新型羧甲基壳聚糖水凝胶的合成与表征

通过1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)/N-羟基琥珀酰亚胺(NHS)催化体系使羧甲基壳聚糖(CMCS)交联,制备了新型羧甲基壳聚糖水凝胶.探讨了EDC用量和EDC/NHS质量比对水凝胶特性的影响.CMCS水凝胶具有pH响应特性,在等电位点溶胀率最小.降解实验结果表明,水凝胶浸泡在磷酸盐缓冲溶液中,10 d失重率在15%~45%之间,主要是未交联部分溶解所致.而浸泡在含有0.2 mg/mL溶菌酶的磷酸盐缓冲溶液中,低交联度水凝胶80 h基本降解,高交联度水凝胶不易降解.初步研究了CMCS水凝胶包埋牛血清白蛋白(BSA)的释放行为.     

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     

羧甲基纤维素-壳聚糖水凝胶球的制备及性能

采用物理交联法制备了羧甲基纤维素(CMC)-壳聚糖(CS)共混水凝胶球;研究了共混球的耐酸碱性、溶胀性及对亚甲基蓝的吸附性能.结果表明,水凝胶球在弱酸和弱碱中具有一定的稳定性;随着羧甲基纤维素与壳聚糖质量比的增大,水凝胶的吸水溶胀率增加.在CMC与CS质量比为1∶4时制备的水凝胶呈规则球状.     

聚乙烯醇/羧甲基壳聚糖共混水凝胶的辐射合成及性能

采用电子加速器辐照法制备了聚乙烯醇(PVA)/羧甲基壳聚糖(CMCH)共混水凝胶;研究了PVA与CMCH的配比、辐照剂量、温度以及pH值对PVA/CMCH共混水凝胶性能的影响.实验发现,PVA与CMCH在辐照剂量为40 kGy、配比为w(PVA)/w(CMCH)=5/1的条件下可得到强度较好的PVA/CMCH共混水凝胶,该水凝胶具有一定的温度和pH敏感性:在5~20℃时具有较高的溶胀率,温度在20℃以上溶胀率较低;水凝胶在pH<4.0和pH>6.0时溶胀率均较大,而当pH为4.0~6.0时溶胀率较小.     

温敏性乙二醇壳聚糖水凝胶的制备及药物缓释性能

以乙二醇壳聚糖为原料, 乙酸酐为酰化剂, 通过N-乙酰化反应, 制得了新型温敏性高分子乙酰化乙二醇壳聚糖. 通过核磁共振氢谱(¹H NMR)、 傅里叶变换红外光谱(FTIR)及试管倒置法对乙酰化乙二醇壳聚糖的结构及温敏性进行了表征, 通过扫描电子显微镜(SEM)和紫外-可见分光光度计(UV-Vis)对水凝胶的微观形貌和体外药物释放性能进行了研究. 结果表明, 随着反应时间和乙酸酐与乙二醇壳聚糖氨基摩尔比的增加, 产物的乙酰度逐渐增加; 乙酰化乙二醇壳聚糖溶液具有热可逆温敏性溶胶-凝胶转变行为, 可以通过控制乙酰化乙二醇壳聚糖的乙酰度和溶液浓度, 使溶胶-凝胶转变温度处于室温至体温(25~37 ℃)之间; 乙酰化乙二醇壳聚糖水凝胶具有“高度孔隙化且孔隙之间相互连通”的结构特点, 通过控制乙酰度和溶液浓度, 可使其孔径大小处于1~40 μm范围内; 乙酰化乙二醇壳聚糖水凝胶的乙酰度为89.90%时, 质量分数为5%~7%的水凝胶对抗癌药物吉西他滨具有缓释作用, 载药凝胶的释药时间可达3~5 d. 乙酰化乙二醇壳聚糖有望在药物释放及组织工程等领域得到广泛应用.     

两亲型羧甲基壳聚糖衍生物的合成及体外药物释放

通过羧甲基壳聚糖与醛和乳糖反应制得N-烷基乳糖基-O,N-羧甲基壳聚糖,并以戊二醛为交联剂制成水凝胶;以人血清蛋白作为模型药物,初步探讨了该水凝胶对蛋白类药物的释放规律。结果表明:该水凝胶具有亲水-疏水两亲性和不同于壳聚糖的pH敏感性,有望应用于蛋白类药物的控制释放。     

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。     

离子凝胶反应法制备壳聚糖/N,O-羧甲基壳聚糖微球

以一氯乙酸与壳聚糖反应形成N,O-羧甲基壳聚糖两性聚电解质,分光光度法测定其等电点IEP=2．86。以此两性聚电解质与壳聚糖可以在一定条件下形成微球,光学显微镜和电子显微镜测试表明,控制两种聚电解质配比可以制备不同粒径大小的微球,而超声功率对微球粒径的影响较小。红外光谱测试表明微球中N,O-羧甲基壳聚糖羧基以羧酸根形式存在,分光光度与电导法联合测定表明两种聚电解质以离子凝胶作用形成微球,其最佳制备条件为IEP（CM-CHITOSAN）〈pH〈pKa（CS）,在此较宽的pH值范围内微球可稳定存在。     

疏水改性凝胶的合成及其药物释放性能的研究

以偶氮二异丁腈为引发剂,通过化学引发聚合合成甲基丙烯酸β-羟乙酯(HEMA)/N-乙烯基吡咯烷酮(NVP)二元共聚物和HEMA/NVP/甲基丙烯酸乙酯(或甲基丙烯酸丁酯)三元共聚物水凝胶,研究了凝胶在不同的酸度介质中对小分子药物阿司匹林的释放过程,结果表明,在模拟胃肠道条件下,随着疏水性单体的加入使凝胶的药物释放速率减缓,可实现药物的控制缓释作用。     

Radiation Synthesis of Superabsorbent Hydrogels Based on Chitosan and Acrylic Acid for Controlled Drug Release

Superabsorbent hydrogels based on the natural polymer chitosan and acrylic acid (CS/AAc) was prepared using ⁶⁰Co gamma radiation as a source of initiation and crosslinking. The factors, which affect the preparation of CS/AAc hydrogels such as irradiation dose, CS/AAc ratios, and acrylic acid monomer concentrations, to get the best optimum conditions, were investigated. The kinetic studies of the swelling of CS/AAc hydrogel showed that it follows a Fickian type of water diffusion. The Fickian constant value ‘n’ was more than 0.5 with a high swelling capacity of 300 g/g as superabsorbent hydrogel. In addition, the suitability of CS/AAc hydrogel as carrier material for the drug Chlortetracycline-HCl has been investigated by adsorption isotherm studies. The performance of drug release from hydrogel systems, influenced by acrylic acid ratio and the effect of pH of the medium was studied.     

Synthesis, Structure and Properties of Novel Quaternized Carboxymethyl Chitosan with Drug Loading Capacity

A modified approach to prepare novel amphipathic octadecyl-quaternized carboxymethyl chitosan (QACMC) was reported, in which carboxymethyl chitosan (CMC), prepared from chitosan, was made to react with glycidyl octadecyl dimethylammonium chloride; thus, the octadecyl quaternary ammonium group was introduced into CMC. The structure and thermal properties of these derivatives were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (¹H-NMR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The crystalline properties of QACMC were perfect, and it had a high degree of crystallinity. All the chitosan derivatives had good thermal stability when the temperature was lower than 200 °C. The moisture-absorption and retention abilities of QACMC were lower than that of hyaluronic acid (HA) and CMC. The carboxymethyl and quaternary ammonium groups did not show a synergistic effect, and the effects of both the molar mass and the hydrophobic side chains of long alkyl moieties were important. Minocycline hydrochloride was successfully incorporated into QACMC polymeric micelles with a remarkably high efficiency (10.9%, mass fraction). QACMC promises to be a high-potential delivery vector for lipophilic drugs.     

新型载药壳聚糖季铵盐的合成、结构与性能

通过羧甲基壳聚糖接枝二甲基十八烷基环氧丙基氯化铵, 制备了一系列不同取代度和分子量的羧甲基壳聚糖十八烷基季铵盐(QACMC). 用傅立叶变换红外(FTIR)光谱、核磁共振谱(1H-NMR)、X射线衍射(XRD)谱、差式扫描量热法(DSC)等对其分子结构、结晶和热性能进行研究, 同时研究QACMC的吸湿保湿性能, 并与透明质酸(HA)、壳聚糖(chitosan)和羧甲基壳聚糖(CMC)进行比较. 结果表明, QACMC具有较好的结晶性和热稳定性, 结晶度可达72.3%; 其吸湿保湿性低于透明质酸(HA)和羧甲基壳聚糖, 而受季铵基团取代度和QACMC分子量的影响, 羧酸盐和季铵盐两种亲水基团对QACMC吸湿性的影响不具有协同作用; QACMC对亲脂性药物盐酸米诺环素的载药率可达10.9%(质量分数), 远高于壳聚糖和羧甲基壳聚糖.     

自黏附、近红外光响应水凝胶的制备及药物释放性能研究

水凝胶是一种亲水的三维网络结构,具有良好的生物相容性,可为细胞的迁移生长提供良好的支撑结构,常被用为细胞或药物的载体。然而,传统水凝胶缺乏对外界刺激的响应行为,难以实现在时间和空间上管理药物的释放。本文通过制备聚多巴胺-聚吡咯(PDA-PPy)纳米粒子,并嵌入聚丙烯酰胺/聚(异丙基丙烯酰胺-co-丙烯酸)(PAM/P(NIPAm-co-AAc))水凝胶网络中,制备了具有近红外光响应的黏附水凝胶,并对其拉伸性能、黏附性、NIR药物可控释放性能进行了讨论。结果表明：1)当PDA-PPy-PAM在水凝胶中的含量增加时,水凝胶的延伸比率呈现先增加(从3倍提高到5倍)后减小的趋势,而水凝胶的断裂应力呈现逐渐下降的趋势(从60 kPa减小到30 kPa);2)所制备的水凝胶对玻璃、塑料和人体皮肤等物体表面可形成良好的黏附效果;3)水凝胶的NIR光热转换率受PDA-PPy纳米含量的影响,且随纳米粒子含量增加而提高,当纳米含量为1.8 wt%时,水凝胶在NIR下辐射10 min后,温度可达到45 ℃左右;4)载有四环素的水凝胶在NIR辐射下,其药物释放量逐渐提高(120 min后,达到55%左右的释放),而未被NIR辐射的水凝胶的药物释放量只有5%,且在揭取一段时间释放的药物溶液用于抗菌实验,结果表明水凝胶在NIR辐射40 min所达到的药物浓度,可达到90%以上的抗菌效率,NIR辐射时间增加至120 min的药物量可达到约100%的抗菌效率。     

（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖/聚乙二醇互穿网络凝胶的制备及其释药作用

将壳聚糖改性为（2-羟基-3-丁氧基）丙基 羟丙基壳聚糖（2-H-3-B-P-HPCS）,并以（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖和聚乙二醇（PEG）为原料制备（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖/聚乙二醇互穿网络凝胶,研究了（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖浓度、聚乙二醇的用量、交联剂戊二醛用量、反应温度对该凝胶溶胀性能的影响。 通过红外光谱分析和扫描电子显微镜的方法比较了壳聚糖、（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖和（2-羟基-3-丁氧基）丙基-羟丙基壳聚糖/聚乙二醇互穿网络凝胶结构和形态上的不同。 以阿昔洛韦为模型药物研究了其释药性能。 结果表明,该凝胶均具有良好的溶胀性、pH敏感性和药物缓释作用,有望用作新型的药物载体。     

A Novel Methacryloyl Chitosan Hydrogel Microneedles Patch with Sustainable Drug Release Property for Effective Treatment of Psoriasis

Psoriasis is a chronic and recurrent skin disease that often requires long-term treatment, and topical transdermal drug delivery can reduce systemic side effects. However, it is still a challenge in efficient transdermal drug delivery for psoriasis treatment due to low penetration efficiency of most drugs and the abnormal skin conditions of psoriasis patients. Here, a safe and effective methacryloyl chitosan hydrogel microneedles (CSMA hMNs) patch is developed and served as a sustained drug release platform for the treatment of psoriasis. By systematically optimizing the CSMA preparation, CSMA hMNs with excellent morphological characteristics and strong mechanical properties (0.7 N needle⁻¹) are prepared with a concentration of only 3% (w/v) CSMA. As a proof-of-concept, methotrexate (MTX) and nicotinamide (NIC) are loaded into CSMA hMNs patch, which can produce a sustained drug release of 80% within 24 h in vitro. In vivo experiments demonstrated that the CSMA hMNs patch can effectively inhibit the skin thickening and spleen enlargement of psoriatic mice and has a good biosafety profile at sufficient therapeutic doses. This study provides a new idea for the preparation of hMN systems using modified CS or other biocompatible materials and offers an effective therapeutic option for psoriasis treatment.     

High Substitution Synthesis of Carboxymethyl Chitosan for Properties Improvement of Carboxymethyl Chitosan Films Depending on Particle Sizes

This study investigated the effect of chitosan particle sizes on the properties of carboxymethyl chitosan (CMCh) powders and films. Chitosan powders with different particle sizes (75, 125, 250, 450 and 850 µm) were used to synthesize the CMCh powders. The yield, degree of substitution (DS), and water solubility of the CMCh powders were then determined. The CMCh films prepared with CMCh based on chitosan with different particle sizes were fabricated by a solution casting technique. The water solubility, mechanical properties, and water vapor transmission rate (WVTR) of the CMCh films were measured. As the chitosan particle size decreased, the yield, DS, and water solubility of the synthesized CMCh powders increased. The increase in water solubility was due to an increase in the polarity of the CMCh powder, from a higher conversion of chitosan into CMCh. In addition, the higher conversion of chitosan was also related to a higher surface area in the substitution reaction provided by chitosan powder with a smaller particle size. As the particle size of chitosan decreased, the tensile strength, elongation at break, and WVTR of the CMCh films increased. This study demonstrated that a greater improvement in water solubility of the CMCh powders and films can be achieved by using chitosan powder with a smaller size.     

磁性壳聚糖微球的制备、表征及其靶向给药研究

磁性微球;阿司匹林;磁性壳聚糖微球的制备、表征及其靶向给药研究     

Synthesis and Drug Release Properties of Thermosensitive Poly(N-vinylacetamide-co-vinylacetate) Hydrogels

Thermosensitive poly[N-vinylacetamide-co-vinylacetate][P(NVA-co-VAc)] hydrogels were prepared via free radical copolymerization from hydrophilic NVA and hydrophobic VAc in the presence of butylenes-bis (N-vinylacetamide)(Bis-NVA) as crosslinker. Scanning electron microscopy(SEM) images reveal that the as-prepared hydrogels were of three-dimensional network with irregular cave structure. The prepared hydrogels with more NVA in the feed swelled faster and the swelling ratio of the hydrogels gradually decrease...     

壳聚糖-g-聚甲基丙烯酸凝胶粒的制备及其药物释放行为

以壳聚糖和甲基丙烯酸为原料,硝酸铈铵为引发剂,合成了不同接枝率的壳聚糖-g-聚甲基丙烯酸(CS-g-PMAA),用FTIR、1H NMR和元素分析表征了产物的结构,以柠檬酸三钠和戊二醛为交联剂制备了具有核壳结构的CS-g-PMAA载药体系。 用UV/Vis检测了CS-g-PMAA粒子对模型药物的释放行为。 结果表明,CS-g-PMAA接枝率为12.21%时药物释放速率最慢,其在pH=1.8介质中药物累积释放量(11 h)为44.18%,而壳聚糖粒子的累积释放量高达65.24%,即接枝改性壳聚糖粒子对药物的缓慢控制释放性能较好; CS-g-PMAA粒子的释药行为还依赖于介质的pH值和盐浓度,在低pH值和低盐浓度下,药物释放速率较快;酶环境下由于载体材料的降解使药物释放速率加快。 分析了不同条件下CS-g-PMAA载药粒子中药物的释放机理。