胶原/O-羧甲基壳聚糖复合水凝胶的制备及表征

以I型兔皮胶原蛋白(Col)和O-羧甲基壳聚糖(O-CMC)为原料,采用中和透析法制备了Col/O-CMC复合水凝胶,然后通过扫描电镜和红外光谱对其进行表征,并重点探究O-CMC质量浓度对复合水凝胶的溶胀率、流变性、接触角、体外降解性及抗菌性能的影响。结果表明,Col与O-CMC之间依靠氢键作用力相结合,且随着O-CMC质量浓度的增加,制备所得到的凝胶内部结构趋于致密,当O-CMC的质量浓度为10 mg/mL时,其孔径为(201.32±14)μm、溶胀率为42.78%±1.39%、水接触角为53.91°±0.63°、质量损失率降低至52.95%。此外,复合水凝胶对大肠杆菌的抑制率达到了100%,使其应用于抗菌性支架材料具有广阔的前景。     

聚乙烯醇/季铵盐壳聚糖复合水凝胶的制备及其烫伤敷料的应用

采用聚乙烯醇为基础材料,以季铵盐壳聚糖为抗菌剂,丙三醇为辅料,采用溶液共混法制备聚乙烯醇/季铵盐壳聚糖复合水凝胶作为皮肤烫伤敷料,通过流变实验、抗菌实验、细胞实验以及动物活体实验考察复合水凝胶的综合性能。结果表明,制备的复合水凝胶具有适宜的粘度(22~35Pa·s),涂覆于皮肤表面呈现较好的粘附性能;对大肠杆菌和金黄色葡萄球菌均有良好的抑菌作用,同时具有优良的细胞相容性;复合水凝胶敷料对皮肤刺激极小,昆明鼠深Ⅱ度烫伤修复实验表明,凝胶敷料可有效加快创面愈合速度以及瘢痕的形成,创面愈合从一般的数周缩减至3周左右,大大缩短创面修复时间,且愈后瘢痕组织小。     

聚乙烯醇/海藻酸钠复合水凝胶的制备及电场响应性能

将聚乙烯醇和海藻酸钠的混合水溶液通过凝固浴凝固,再通过反复冷冻-解冻的方法制备出交联的水凝胶。该水凝胶在NaCl水溶液中加直流电场后表现出溶胀、收缩、弯曲行为。该凝胶的弯曲速度和最大弯曲度随电压及NaCl溶液浓度的增加而增大,最大形变量随凝胶中的海藻酸钠含量的增加而增大。     

己酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶的制备及其药物缓释性能

为减少泊洛沙姆水凝胶的溶胶-凝胶转变温度对浓度的依赖性,以泊洛沙姆(P₄₀₇)为基材,将己酰化乙二醇壳聚糖(HGC)与泊洛沙姆复合,制备了己酰化乙二醇壳聚糖/泊洛沙姆(HGC/P₄₀₇)复合水凝胶,利用FTIR、SEM及试管反转法探讨了HGC/P₄₀₇复合水凝胶的性能,并利用紫外-可见分光光度计(UV-vis)对HGC/P₄₀₇复合水凝胶的体外药物缓释性能进行表征。结果表明,通过控制HGC的加入量,基于3%泊洛沙姆的HGC/P₄₀₇复合水凝胶即可发生溶胶-凝胶转变现象,并使HGC/P₄₀₇复合水凝胶的溶胶-凝胶转变温度处于32~37℃。HGC/P₄₀₇复合水凝胶具有高度孔隙率,孔隙之间相互连通,孔径大小处于10~90μm的范围之内。HGC/P₄₀₇复合水凝胶对抗癌药物吉西他滨的释药量达到82.4%~90.6%,缓释时间可达80 h左右。HGC/P₄₀₇复合水凝胶在可注射药物载体领域具有重要的应用前景。     

不同条件对PVA/CS复合水凝胶溶胀性能的影响

以聚乙烯醇(PVA)、壳聚糖(CS)为原料,戊二醛为交联剂,制备出PVA/CS复合水凝胶载体材料,改变PVA/CS的质量配比、交联剂含量、pH值和温度,考察了不同条件下对复合水凝胶溶胀性能的影响.结果表明,当PVA/CS质量比为3:1、交联剂体积分数为4%时所合成凝胶的溶胀性能较好;随着温度的升高,溶胀度不断减小;凝胶在酸性条件的溶胀性能远远优于碱性条件的溶胀性能.     

纳米掺锶羟基磷灰石/聚乙烯醇/明胶复合水凝胶的制备及矿化性能研究

采用化学沉淀法制备纳米纳米掺锶羟基磷灰石(Sr-HAP)粉体,通过物理法工艺加入聚乙烯醇(PVA)和明胶溶液,经反复冷冻-解冻制备纳米掺锶羟基磷灰石/聚乙烯醇/明胶(Sr-HAP/PVA/明胶)复合水凝胶。利用红外光谱、X射线衍射、扫描电镜对产物的结构进行分析,采用模拟体液法对复合凝胶产物的再矿化行为进行分析。结果表明:实验所制备的复合水凝胶组成均一,凝胶内部Sr-HAP分散良好、分布均匀,且含有大量网状结构,符合理想组织工程支架材料高孔隙率的要求。产物在模拟体液中浸泡15d后,经扫描电镜分析发现凝胶表面有沉积物生成,X射线衍射检测表面沉积物含有类似HAP的物质,说明复合凝胶具有诱导性,有望作为软骨或组织修复材料进一步研究。     

壳聚糖-甘油磷酸钠温敏凝胶的制备与表征

制备了壳聚糖-甘油磷酸钠温敏凝胶,讨论了壳聚糖的脱乙酰度,浓度和β-GP的浓度等工艺参数对温敏凝胶理化性能的影响,通过X射线,红外光谱和扫描电镜等测试手段表征了温敏凝胶材料的成分组成和微观结构,讨论了该体系的自凝化机理.     

自修复氧化海藻酸钠-羧甲基壳聚糖水凝胶的制备及药物缓释性能

本研究基于动态亚胺键合成了一种具有自修复性能的氧化海藻酸钠-羧甲基壳聚糖水凝胶(OSA-CMCS).通过海藻酸钠的糖醛酸,合成了OSA,并通过与CMCS的席夫碱反应制备了具有不同交联度的自修复OSA-CMCS水凝胶,研究了OSA-CMCS水凝胶的微观形态、黏弹性能、溶胀性能、自修复性能、酶促降解性能和体外药物释放性能....     

纳米材料掺杂型聚乙烯醇双交联复合水凝胶的力-化学性质

以聚乙烯醇(PVA)为原料,氧化石墨烯(GO)和羟基磷灰石(HA)为共掺杂物,先以戊二醛作为交联剂,采用化学交联法制备了GO/HA/PVA单网络单交联复合水凝胶,再通过循环冷冻-解冻技术使PVA聚合物链间进一步发生氢键交联,制备得到GO/HA/PVA双网络双交联复合水凝胶。采用HRSEM、XRD表征了水凝胶的微观形貌和晶相结构,并研究了GO与PVA、HA与PVA在不同质量比及不同冷冻-解冻循环次数时制备所得GO/HA/PVA复合水凝胶的力学性能。结果表明:随着GO与PVA质量百分比的增加(0%～2.6%),该凝胶拉伸力学强度不断增强;随着HA与PVA质量比的增加(0.22～1.10),该凝胶的拉伸强度先增强后减弱;随着冷冻-解冻循环次数增加(0次、3次、7次)该凝胶的拉伸强度逐渐增强,弹性模量也逐渐提高。当GO与PVA质量百分比为1.9%、HA与PVA质量比为0.66、冷冻-解冻循环次数N=7次时,制备所得凝胶的拉伸力学性能最优(拉伸强度为695 kPa,断裂应变为286%,弹性模量为78 kPa)。此外,深入研究了不同冷冻-解冻循环次数对水凝胶含水率和溶胀率的影响规律。结果表明:不同冷冻-解冻循环次数(0次、3次、7次)的凝胶含水率为79.3%～81.7%,平衡溶胀率为50.1%～72%,且均在60 min后达到溶胀平衡。该水凝胶有望作为软骨替代材料应用于临床医学领域。     

Alginate microsphere-collagen composite hydrogel for ocular drug delivery and implantation

A composite collagen hydrogel containing protein encapsulated alginate microspheres was developed for ocular applications. Bovine serum albumin (BSA) served as a drug model. The composite hydrogel retained optical clarity and mechanical robustness of control hydrogels without microspheres. A sustained release of BSA was achieved during an 11-day period in neutral phosphate buffer. The composite hydrogel supported human corneal epithelial cell growth and had adequate mechanical strength and excellent optical clarity for possible use as therapeutic lens for drug delivery and/or use as corneal substitute for transplantation into patients who have corneal diseases.     

Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide

Purpose: In this study, a thermosensitive in situ gelling vehicle was prepared to increase the precorneal resident time and the bioavailability of methazolamide (MTA). Method: Poloxamer analogs were used as the gelling agents, and the in situ gel was obtained by using a cold method. The gelation temperature, rheological properties, in vitro release as well as in vivo evaluation (the elimination of MTA in aqueous humor and intraocular-lowering effect) of the optimized formulations were investigated. Results: The optimum concentrations of poloxamer analogs for the in situ gel-forming delivery system were 21% (w/w) poloxamer 407 and 10% (w/w) poloxamer P188. This formulation was able to flow freely under nonphysiological conditions and underwent sol–gel transition in the cul-de-sac upon placement into the eye. In vitro release studies demonstrated a diffusion-controlled release of MTA from the poloxamer solutions over a period of 10 hours. In vivo evaluation indicated that the poloxamer solutions had a better ability to retain drug than MTA eyedrops did. Conclusion: These results suggested that in situ gelling ophthalmic drug delivery system may hold some promise in ocular MTA delivery.     

PAA/PVA互穿网络水凝胶膜的制备和药物输送研究

采用自由基溶液聚合和连续的互穿网络技术,以氧化还原引发体系为引发剂、化学交联聚丙烯酸(PAA)和聚乙烯醇(PVA)制备了一系列PAA/PVA水凝胶膜.ATR-FTIR光谱表明,网络组成之间形成了新的相互作用的氢键,DSC分析表示网络组成具有良好的热力学相容性.膜在各种介质中的溶胀性质表明:因PAA的亲水性强于PVA,溶胀比随PAA的增多而提高.以阳离子化合物结晶紫为模板药物考察了在不同的pH缓冲溶液中的释放行为,结果表明,药物的释放能力可以通过改变体系的pH值加以调控.     

Chitosan-based thermosensitive hydrogel containing liposomes for sustained delivery of cytarabine

Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2 +/- 2.58%) with the mean diameter of 220 +/- 6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t(1/2) (28.86 h) and AUC 2526.88 mug/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.     

Preparation and evaluation of gel formulations for oral sustained delivery to dysphagic patients

Background: Oral sustained release gel formulations may provide a means of administering drugs to dysphagic and geriatric patients who have difficulties with handling and taking oral dosage forms. Aim: We have designed gel formulations for the oral administration of paracetamol with suitable rheological characteristics for ease of administration to patients with swallowing difficulties and sufficient integrity in the acidic environment of the stomach to achieve a sustained release of this drug. Method: Gels formed by gelatin, agar, gellan, pectin, and xyloglucan were assessed for suitable gel strength and in vitro and in vivo release characteristics. Results: Gellan (1.5%?w/v) and xyloglucan gels (1.5%?w/w) had acceptable gel strengths for ease of swallowing and retained their integrity in the rat stomach sufficiently well to sustain the release of paracetamol over a period of 6 hours. Comparison of 1.5%?xyloglucan gels with a commercially available preparation with identical paracetamol concentrations demonstrated improved sustained release properties of the xyloglucan gels. Conclusions: Gels formed by gellan and xyloglucan have suitable rheological and sustained release characteristics for potential use as vehicles for oral delivery of drugs to dysphagic patients.     

Hydroxybutyl chitosan thermo-sensitive hydrogel: a potential drug delivery system

Drug delivery mediated by hydrogel has shown great promise in controlled drug release field. We report here the development of a hydroxybutyl chitosan (HBC) thermo-sensitive gel to deliver doxorubicine hydrochloride (DOX·HCl) for cancer treatment. Concentrated HBC aqueous solution could transform into hydrogel within 30 s after injection under physiological temperature in non-chemical fashion. The properties of the HBC gels including chemical structure, surface morphology, and rheologic properties were studied. Gelation temperature and gelation time of HBC could be adjusted by HBC concentrations. The gel erosion rate in vivo was faster than solubilization rate in vitro. The mild inflammatory response caused by implantation of the hydrogel was acceptable. The DOX·HCl (1 mg/ml) loaded HBC gels displayed slow release rates that were independent of the HBC concentration, and significantly reduced viability of 4T-1 cells compared with the HBC gels after 1 day incubation. These results indicate that thermo-sensitive HBC hydrogels have promising potential as an injectable drug carrier for pharmaceutical applications.     

Development of pH sensitive polyacrylamide grafted pectin hydrogel for controlled drug delivery system

In the present study an attempt was made to graft polyacrylamide on pectin. The grafted polymer was characterized by FTIR spectroscopy, differential scanning calorimetry and X-ray diffraction. Rheological property of pectin solution was compared with the product solution. The grafted polymer was cross-linked with varying amount of glutaraldehyde. The swelling properties of the cross-linked product were also studied. The salicylic acid, an antipyretic drug, was incorporated in the cross-linked gel as a model drug and the drug release studies were done in a modified Franz’s diffusion cell. The effect of cross-linking density on the release property of salicylic acid was studied through the cross-linked product. The product showed better film forming property and gelling property than pectin. The comparative rheological properties of pectin and grafted copolymer indicated change in the property of the product. FTIR studies indicated incorporation of amide group. Differential scanning calorimetry and XRD suggested formation of a new polymer. Swelling study indicated pH dependent swelling of the cross-linked hydrogel. Salicylic acid release indicated pH dependent release from the hydrogel.