新型生物黏附性材料巯基壳聚糖的合成与表征

巯基聚合物利用二硫键的形成, 以共价键黏附于黏膜表面, 可以延长药物在黏膜上的滞留时间, 有利于药物分子的吸收. 本文合成了一种新型巯基聚合物——N-乙酰基-L-半胱氨酸-g-壳聚糖(CS-NAC), 并进行了表征, 同时对材料的溶胀度、黏附性和细胞毒性进行了测试. 结果表明, 这种巯基聚合物具有较高的巯基含量, 最高可达到589.3 μmol/g; 具有快速的溶胀性能; 黏附性显著增强, 黏附时间和黏附力分别是壳聚糖的30和3倍; 无明显的细胞毒性. 因此, CS-NAC是一种很有应用前景的生物黏附性材料.     

光响应智能生物粘附材料的设计与应用

智能生物粘附材料是一类通过生物粘附作用粘附于组织表面,且对外界刺激具有特定响应的新型粘合剂.因其止血快、生物相容性好、生物粘附性强且具有智能响应效果而在外科临床应用领域受到了极大的关注.其中,光响应生物粘附材料因具有无接触、时空调节、严格剪裁和远程控制等独特优势,被广泛用于伤口止血及组织修复等领域.除了广泛应用的紫外光,可见光和近红外光因其优异的组织穿透深度、高稳定性和低能量特性而在这类光响应生物粘附材料中受到广泛关注.本文总结了智能响应粘附材料的响应类型,重点介绍了近年来光响应生物粘附材料的研究进展,包括分类、性能及其在生物医学领域的具体应用等.     

含悬挂羧基手臂聚乳酸材料的合成与血小板粘附性研究

制备了乳酸-β-苹果酸共聚物,并在此基础上进一步修饰合成了含悬挂羟基(PLMAHE)以及悬挂羧基(PCA-PLA)的聚乳酸共聚物,利用原子力显微镜及环境扫描电镜,观察了聚合物膜的表面形貌以及粘附在聚合物膜上的血小板数量与形态.结果表明含悬挂羟基材料表面粘附血小板时发生聚集并有伪足生成,含悬挂羧基材料表面血小板粘附数量较少且形态正常,有望成为优良的抗凝血材料.     

仿贻贝粘附蛋白聚合物的研究及动态

贻贝粘附蛋白以其对不同基材表面及在水下都具备高强的粘附能力而闻名。根据仿生学原理,通过将贻贝粘附蛋白功能元即邻苯二酚基团与合成高分子相结合制备仿贻贝粘附蛋白聚合物,达到复制重现甚至超越天然贻贝粘附蛋白粘附效力的目的,是目前贻贝仿生领域研究热点之一。本文综述了近年来国内外仿贻贝粘附蛋白聚合物的研究进展。我们按照主链结构的种类进行了分类,对仿贻贝粘附蛋白聚合物材料的发展过程、材料的设计思路以及应用领域进行了系统的归纳总结。通过研究分子结构与仿生材料功能特性之间的相互关系,希望为以后设计合成新型的功能化的贻贝仿生材料提供有益的借鉴和参考。     

含巯基/二硫键聚合物生物材料

含巯基/二硫键聚合物生物材料具有多种良好的性能,作为药物、基因等的释放载体在生物医学领域具有广泛的应用前景。随着基因工程和组织工程的发展,含巯基/二硫键聚合物生物材料的可生物降解性得到高度重视,而怎样改善其降解性能成为限制其应用的关键因素。由于二硫键在细胞外环境里保持稳定,在细胞溶质的还原环境中容易发生断裂,因此在制备新型基因、药物等释放载体上,二硫键充当了重要的角色,它的引入为聚合物生物材料的生物降解性能的设计与改善提供了一条重要的途径。本综述重点以聚合物水凝胶、聚合物微胶束、囊泡等为例,从巯基/烯的光聚合反应、Michael加成反应、氧化还原反应的角度,介绍了巯基/烯在聚合物中形成二硫键的不同途径的研究进展,并详细论述了基因载体、蛋白质载体、小分子药物载体三种还原敏感型材料的制备、表面修饰和改性的进展情况,进一步强调含巯基/二硫键聚合物生物材料的研究在生物医学领域应用的重要性。     

高粘附可拉伸高分子材料与高动态稳定人体电生理监测

高动态稳定人体电生理监测在智能可穿戴健康监测、心血管疾病临床诊断、神经系统疾病治疗以及智能人机交互等领域具有广阔的应用前景.作为人与外部环境的信号交互桥梁,皮肤电极可贴合于皮肤表面,以无创的方式监测和采集各种电生理信号,成为高动态稳定电生理监测的理想平台.从材料角度出发,皮肤电极的高动态稳定性决定于基底材料的高粘附性和可拉伸性.因此,如何通过高分子结构的合理设计制备高粘附可拉伸高分子材料,构筑高度共形粘附于人体皮肤表面的电极,从而实现高动态稳定人体电生理监测,是柔性智能健康监测领域的重要研究方向.本文总结了本课题组近年来在高粘附可拉伸高分子材料制备及其在高动态稳定人体电生理监测应用方面的研究进展,并讨论了高粘附可拉伸高分子材料在下一代柔性智能健康监测领域面临的机遇和挑战.     

聚氨酯表面构建磺铵两性离子结构及其抗血小板粘附性的研究

通过己二异氰酸酯(HDI)在聚醚氨酯(PU)表面构建磺铵两性离子结构,以改善其不凝血性能,首先用HDI活化PU表面,生成PU-NCO衍生物;然后通过N,N-二甲基乙醇胺(DMEEA)中的-OH和PU表面的-NCO反应生成PU-N(CH₃)₂;最后用丙磺酸内酯(PS)进行开环.生成磺铵两性离子结构,用ATR-IR表征了各步反应,对构建前后材料的抗血小板粘附性能进行了比较,结果表明,磺铵两性离子结构具有优异的抗血小板粘附性.     

新型含悬挂羧基聚乳酸的制备及其血液相容性和细胞粘附性

制备了乳酸-苹果酸共聚物(PLMA), 并在前期工作的基础上制备了悬挂羧基聚乳酸(PLMACA), 考察了手臂长度及端功能基团对改善聚乳酸的血液相容性及细胞粘附性的影响. 结果表明, PLMACA同时具有良好的血液相容性和细胞亲和性, 极有可能成为新一代血管(修复)材料.     

桑蚕丝素-RGD融合蛋白的固态结构及其细胞粘附性分析

利用基因工程方法把含有短肽RGD的氨基酸序列连接到桑蚕丝素蛋白的结晶序列GAGAGS上, 通过调节DNA的聚合度, 合成了具有[TGRGDSPA(GVPGV)₂GG(GAGAGS)₃AS]_n一级结构、不同分子量大小的桑蚕丝素-RGD融合蛋白, 并且通过在M9培养基中添加[3-¹³C]Ala的方法进行融合蛋白的稳定同位素标记. ¹³C CP/MAS NMR结果显示, 融合蛋白中的GAGAGS部分具有与天然桑蚕丝素结晶部分相同的分子结构, 即Silk I处理后为均一的分子结构, 而Silk II处理后为不均一的分子结构, 它包含了三种不同的结构成分. 另一方面, 通过对小鼠成纤维细胞BALB/3T3在不同蛋白材料载体上的粘附和增殖性能的测定结果显示, 融合蛋白对细胞的增殖性能与天然胶原蛋白相近, 但表现出了比胶原蛋白更好的细胞粘附性能. 该研究结果显示, 如果对该桑蚕丝素-RGD融合蛋白进行适当加工, 可能适合于组织工程支架材料的应用.     

响应性聚合物纳米材料作为药物载体的研究进展

近年来聚合物纳米材料被应用于药物递送系统的研究,其中刺激响应性聚合物纳米载体因具有载药稳定性好、生物相容性好等特点而成为研究热点,通过各种内在或外在条件给予适当刺激,响应性聚合物纳米载体能达到药物控制释放的目的.本文介绍了几种单一刺激和多重刺激响应性聚合物材料的研究进展及作为抗癌药物载体的优势,并对未来的发展方向进行了...     

Formulation and evaluation of thermoreversible,mucoadhesive in situ intranasal gel of rizatriptan benzoate

The present study was aimed to formulate and evaluate in situ thermoreversible intranasal gel of an antimigraine drug rizatriptan benzoate. The poloxamer 407 and carbopol 934 were used as thermoreversible and mucoadhesive polymers respectively. The gels were prepared with cold method. The phase transition temperature was determined with visual method. The gels were evaluated for their pH, mucoadhesive strength, in vitro release and ex vivo drug permeation through goat nasal mucosa. The histopathological study of the nasal mucosa was carried out to check for its damage during drug permeation. The 18 % w/v poloxamer solution was found to be showing phase transition at physiologic conditions (34–35 °C). As the percentage of carbopol 934 was increased from 0.1 to 0.5 % w/v the gelling temperature was found to be decreased. All formulations were showing mucoadhesive strength above 4,000 dynes/cm². Drug permeation studies have indicated that the drug permeation rate can be increased by using carbopol 934 above 0.3 % w/v concentration. The histopathological evaluation of nasal mucosa after drug permeation study has not shown any evidence of damage. Thus in situ thermoreversible mucoadhesive gel of rizatriptan benzoate can be a promising approach to treat migraine.     

Alginate-magnesium aluminum silicate films for buccal delivery of nicotine

Sodium alginate-magnesium aluminum silicate (SA-MAS) dispersions with nicotine (NCT) were prepared at different pHs and characterized for the particle size and zeta potential, NCT adsorbed by MAS, and flow behavior before film casting. The physicochemical properties, NCT content, in vitro bioadhesive property, and NCT release and permeation of the NCT-loaded SA-MAS films were investigated. This study showed that incorporation of NCT into the SA-MAS dispersions caused a change in particle size and flow behavior and that NCT could be adsorbed by MAS. The formation of protonated NCT at acidic and neutral pHs could interact with negatively charged MAS via an electrostatic force, resulting in the formation of NCT-MAS flocculates/complexes that could act as microreservoirs in the films. The NCT-loaded SA-MAS films prepared at pH 5 yielded the highest NCT content due to non-significant loss of NCT during drying. Moreover, pH of the preparation also affected the crystallinity and thermal properties of the films. The NCT release and permeation across the mucosal membrane of the films could be described using a matrix diffusion controlled mechanism. In addition, the NCT-loaded SA-MAS films also possessed a bioadhesive property for adhesion to the mucosal membrane. This finding suggests that the NCT-loaded SA-MAS films composed of numerous NCT-MAS complexes as microreservoirs demonstrated a strong potential for use as a buccal delivery system.     

Improved Mucoadhesion,Permeation and In Vitro Anticancer Potential of Synthesized Thiolated Acacia and Karaya Gum Combination: A Systematic Study

Thiolation of polymers is one of the most appropriate approaches to impart higher mechanical strength and mucoadhesion. Thiol modification of gum karaya and gum acacia was carried out by esterification with 80% thioglycolic acid. FTIR, DSC and XRD confirmed the completion of thiolation reaction. Anticancer potential of developed thiomer was studied on cervical cancer cell lines (HeLa) and more than 60% of human cervical cell lines (HeLa) were inhibited at concentration of 5 µg/100 µL. Immobilized thiol groups were found to be 0.8511 mmol/g as determined by Ellman’s method. Cytotoxicity studies on L929 fibroblast cell lines indicated thiomers were biocompatible. Bilayered tablets were prepared using Ivabradine hydrochloride as the model drug and synthesized thiolated gums as mucoadhesive polymer. Tablets prepared using thiolated polymers in combination showed more swelling, mucoadhesion and residence time as compared to unmodified gums. Thiol modification controlled the release of the drug for 24 h and enhanced permeation of the drug up to 3 fold through porcine buccal mucosa as compared to tablets with unmodified gums. Thiolated polymer showed increased mucoadhesion and permeation, anticancer potential, controlled release and thus can be utilized as a novel excipient in formulation development.     

On the CO2 permeation of uniaxially drawn polymers

The CO₂ permeation coefficient and the difficient were measured using the permeation time-lag method for films of atactic polystyrene and high-density polyethylene, each as a function of uniaxial draw ratio. The reduction of permeability with draw ratio is observed for polystyrene and for polyethylene. In the latter it is associated with an increase in crystallinity. In both cases the premeability decreases and the solubility constant remains unchanged. The reduction of permeability is thus caused only by the reduction in diffusion of CO₂ in the drawn polymers. The mechainism is different for the two polymers, as is confirmed by measurements of birefringence, glass transition temperature, and crystallinity.     

Nanostructured Lipid Carriers (NLC)-Based Gel Formulations as Etodolac Delivery: From Gel Preparation to Permeation Study

Topical administration of drug is an attractive alternative to the oral administration as it provides a reduction in adverse reactions and an enhancement of therapeutic effects. The use of lipid carriers in hydrogel structures makes it possible to introduce lipophilic substances in a dissolved form. In this study, an NSAID from the BCS class II, etodolac (ETD), was used. The nanostructured lipid carriers (NLC) obtained with ETD were incorporated into semi-solid forms (gels). Hydrogels with the suspended drug and oleogel were also prepared for comparison purposes. The obtained gels were tested in terms of pH, viscosity, rheological, mechanical, and bioadhesive properties. The release and permeation through membranes were also studied. All tested formulations were characterized by a pH below 7, which ensured the physiological state of the skin. The viscosities of all gels decreased with increasing shear rate, indicating non-Newtonian behavior. The fastest ETD release was observed for NLC with a Carbopol base (formulation F1); a similar result was noticed in the permeation test. The developed gel formulations containing ETD-NLC dispersion and Carbopol or Poloxamer as gelling agents were stable and possessed beneficial pharmaceutical properties.     

Bioadhesive properties of Gantrez nanoparticles

Bioadhesive nanoparticles have been proposed as carriers for the oral delivery of poorly available drugs and facilitate the use of this route. This work summarises some experiments describing the bioadhesive potential of Gantrez nanoparticles fluorescently labeled with rhodamine B isothiocyanate. The adhesive potential of Gantrez was found to be stronger when folded as nanoparticles than in the solubilised form. Conventional nanoparticles displayed a tropism for the upper areas of the gastrointestinal tract, with a maximum of adhesion 30 min post-administration and a decrease in the adhered fraction along the time depending on the given dose. The cross-linkage of nanoparticles with increasing amounts of 1,3-diaminopropane stabilised the resulting carriers and prolonged their half-life in an aqueous environment; although, the adhesive capacity of nanoparticles, the intensity and the relative duration of the adhesive interactions within the gut as a function of the cross-linking degree. Finally, nanoparticles were coated with either gelatin or albumin. In the first case, the presence of gelatin dramatically decreased the initial capacity of these carriers to interact with the gut mucosa and the intensity of these phenomenons. In the latter, bovine serum albumin coated nanoparticles (BSA-NP) showed an important tropism for the stomach mucosa without further significant distribution to other parts of the gut mucosa.     

Mechanism of diffusion of water in carbon black filled polymers

Penetration and permeation of water into polyethylene based polymers filled with carbon blacks was studied as a function of composition using radiochemical and gravimetric methods. The water absorption capacity of the filled polymers depends mainly on the oxygen content of the carbon black particles and the rate of penetration is inversely proportional to the filler loading. A mechanism of water diffusion consistent with permeation experiments is proposed.     

Novel Poly(amidoamine)-Based Hydrogels as Scaffolds for Tissue Engineering

Summary: Poly(amidoamine)s are biocompatible biodegradable polymers, which can be easily functionalized with a number of bioactive and biomimetic compounds. Co-polymerization of these polymers with 4-aminobutyl guanidine (agmatine) leads to an RGD mimicking structure. Hydrogels based on this structure showed an enhanced cell adhesion and could be chemically linked to a glass substrate to create a bioadhesive support for cell growth. Preliminary optimization and cell adhesion tests on Madin-Darby Canine Kidney cells were performed, both on functionalized and non-functionalized structures, with promising results.     

Gel permeation chromatographic studies of the degradation of polyethylene with fuming nitric acid. II. Bulk polyethylene

Preliminary results are reported on the use of gel permeation chromatography in morphological studies of bulk polymers and fibres. Several samples of bulk isotropic and drawn polyethylene were analyzed by gel permeation chromatography following nitric acid oxidation. In all cases suitable samples showed two peaks in the molecular weight distribution, suggesting a qualitative similarity with results for single crystals. It is concluded that the present data are consistent with chain folding in bulk polymers, both in the isotropic and oriented states, with a less degree of regularity than exists in single crystals.