药物缓释载体用温敏性水凝胶

近年来温敏性水凝胶作为药物缓释载体的研究十分广泛。本文在简要介绍了温敏性水凝胶的结构与性质、蛋白质的包埋技术和释药机理后,较为详细地综述了温敏性水凝胶在药物控制释放领域中的应用情况。     

影响聚乙二醇-g-壳聚糖载药体系的一些因素北大核心CSCD

聚乙二醇-g-壳聚糖可以作为抗肿瘤药物、基因、多肽等多种生物大分子的载体,是一种优良的药物载体。聚乙二醇接枝壳聚糖可以改善壳聚糖的水溶性,保护聚乙二醇-g-壳聚糖纳米不被网状内皮系统(RES系统)识别和清除,促进纳米粒子在体内的长循环,将药物更有效地靶向目标组织。目前,聚乙二醇-g-壳聚糖作为药物载体在生物医药领域发挥着重要作用,本文就聚乙二醇-g-壳聚糖的特点,以及在机体的靶向性、缓释等提高药物疗效的关键因素做一论述。     

壳聚糖作为药物缓释载体的研究进展

壳聚糖作为药物缓释载体在减少给药次数,降低药物毒副作用,提高药物疗效等方面具有重要作用。本文综述了壳聚糖作为药物缓释载体的研究进展,主要包括壳聚糖纳米粒子、微球、片、膜和凝胶等的制备和缓释特性,并对其发展趋势进行了展望。     

从L-丝氨酸合成手性环状磷脂的替加氟(Tegafor)和尿苷缀合物

磷脂不仅具有广泛的生物、生理活性,而旦也可以作为药物的有效载体。由药物与磷脂组成的缀合物作为前药,经磷脂的载体功能到达作用部位,再被降解释放出药物分子和磷脂分子,发挥药物作用,达到提高疗效、降低毒性的目的。     

交联聚乳酸中空微球的制备与表征

由于聚乳酸具有良好生物相容性与降解性,故可用作控释给药系统的载体材料．有关聚乳酸及其共聚物微球药物载体、释放行为及微球表面引入基团使之功能化的方法研究已有报道．以其它生物大分子材料作为囊壁材料的缓释微胶囊也有报道,但以聚乳酸制备中空微囊型的药物释放载体却鲜有研究．通过控制分子量、微囊大小、囊壁厚度等参数,     

天然多糖类纳米凝胶药物载体的研究进展

天然多糖具有来源广泛、价格低廉、良好的生物相容性和生物可降解性等特点,被广泛应用于药物载体研究。天然多糖纳米凝胶内部交联网络结构能有效提高药物的稳定性,且自身带有大量的活性官能团,可以被修饰上靶向配体或者对病灶环境敏感的基团,使药物顺利到达靶向细胞,从而实现药物的可控释放,在提高药效的同时降低药物的毒副作用。该综述介绍了天然多糖类纳米凝胶作为药物载体的研究进展,包括壳聚糖、右旋糖酐、普鲁兰多糖、海藻酸盐、透明质酸以及肝素等天然多糖纳米凝胶用于环境响应药物可控释放和靶向药物治疗的研究状况,并对其未来发展方向进行了展望。     

肝素在生长因子控制释放中的应用*

典型的抗凝血药物肝素作为硫酸化的多糖在体内具有多重生物活性,而这些生物活性是通过与生长因子和细胞因子等蛋白质的相互作用来发挥的。由于它与肝素亲和性生长因子具有特异的糖胺聚糖-蛋白质相互作用,近年来被广泛地应用于生长因子的控制释放中,以达到稳定负载于载体材料特别是水凝胶载体中的生长因子并保持其生物活性、延缓释放的作用。本文介绍了近年来肝素在组织工程用生长因子控制释放系统中应用研究的最新进展。     

生物高分子材料在药物传递系统中的降解 Ⅱ.降解动力学及应用

生物高分子材料在现代药物传递系统中不仅起着载体的作用,而且同时影响和控制药物的缓释机理。文章是《生物高分子材料在药物传递系统中的降解Ⅰ.机理与表征方法》的续篇,主要阐述了生物高分子材料在药物传递系统中的降解动力学。     

生物降解聚酯包埋利福平缓释微球的制备及释放行为

以生物可降解乙交酯和丙交酯的无规共聚物(PLGA)为载体,将抗结核病药利福平溶解于PLGA的有机溶液中,采用通常乳化-溶剂挥发方法制备了药物缓释微球.研究了影响微球制备的工艺条件.用电子显微镜观察了微球及降解后的表面形态,测定了微球粒径及载药量,评价了载药微球的体外释放行为.结果表明,以质量分数为1%的明胶为稳定剂,制备的微球形态完整,粒径范围为10～30μm,微球中利福平的平均质量分数为24.3%.体外释药时间可以通过高分子的降解速率来调控,本实验的释药时间可以在42～84d之间调控,药物缓释达到了理想的零级动力学释放.因此,利福平PLGA微球具有显著的长效、恒量药物缓释作用.     

两种医用胶原膜 60Co辐照改性的比较

胶原作为一种新型生物材料,具有无毒,良好的生物相容性,生物可降解性及可吸收性,广泛用于皮肤创伤的治疗、骨缺损的修复、药物缓释的载体、止血敷料、组织工程支架材料等。但胶原在体内降解太快,不能与组织再生速度相匹配。有必要探讨胶原生物材料的改性方法,便于其更好     

Behavior of a Chitosan–Drug System during Diffusion Processes

The process of water vapor sorption by medical chitosan films and the release of nonelectrolyte drugs from these films are investigated. It is shown that the nonelectrolyte drugs are unable to modify the chitosan matrix and cannot provide a prolonged drug release. The modification of chitosan–drug films, for example, by isothermal annealing or transition from the salt form of chitosan to the base one, is required to decelerate the release of drugs from the films.     

Acetaminophen particle design using chitosan and a spray-drying technique

In this study matrices were prepared from particles of poorly water-soluble drugs such as acetaminophen (Act) to determine the drug release rate from these matrix particles. The matrix particles were prepared by incorporating drugs into chitosan powder (Cht, carrier) using a spray-drying method. The formation of composite particles was confirmed by scanning electron microscopic (SEM) analysis. The matrix particles prepared by spray-drying were spherical with a smooth surface. The crystallinity of acetaminophen in the composite particles was evaluated by powder X-ray diffraction and differential scanning calorimetry (DSC). The degree of crystallinity of acetaminophen in the matrix particles decreased with a reduction in the weight ratio of acetaminophen relative to the carrier. These results indicate that a solid dispersion of acetaminophen in chitosan forms matrix particles. The interaction between acetaminophen and chitosan was also investigated by FT-IR analysis. FT-IR spectroscopy of the acetaminophen solid dispersion suggested that the carbonyl group of acetaminophen and the amino group of chitosan formed a hydrogen bond. There were some differences at pH levels of 1.2 and 6.8 in the release of acetaminophen from the physical mixture compared to the matrix particles. At pH 1.2, the release from the matrix particles (Act : Cht=1 : 5) was more sustained than from the physical mixtures. The 70% release time, T70, of acetaminophen from the matrix particles (Act : Cht=1 : 5) increased in pH 1.2 fluid by about 9-fold and in pH 6.8 fluid by about 5-fold compared to crystalline acetaminophen. These results suggest that matrix particles prepared by spray-drying are useful as a sustained release preparation.     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Native and polymeric β-cyclodextrins in performance improvement of chitosan films aimed for buccal delivery of poorly soluble drugs

β-Cyclodextrin (βCD) and its soluble polymeric derivative (EPIβCD) were used to improve the effectiveness of chitosan-based bucco-adhesive film formulations containing bupivacaine hydrochloride and triclosan as poorly-soluble model drugs. The film formulations were characterized in terms of swelling, mucoadhesion and in vitro drug release, while possible interactions between the components were investigated by DSC and FTIR analyses. For both drugs EPIβCD showed a higher solubilizing efficiency than βCD; however cyclodextrin effectiveness in improving the release rate from film formulations was influenced by their different interactions with chitosan. Free βCD acted as a channelling agent, favouring the film swelling, while EPIβCD due to interaction with chitosan caused an opposite effect. βCD was the optimal partner for bupivacaine-loaded films in terms of film swelling, mucoadhesion and drug release. Contrariwise, EPIβCD was the best partner for triclosan-loaded films, allowing the highest drug release rate increase, due to its higher solubilizing ability with respect to βCD. Addition of the suitable cyclodextrin enabled formulation of buccal films with suitable drug release properties.     

Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug

Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability.     

Stimuli-responsive multilayer chitosan hollow microspheres via layer-by-layer assembly

Novel stimuli-responsive multilayer chitosan hollow microspheres with chitosan as the unique component have been fabricated by the sequential layer-by-layer electrostatic assembly technique from the sacrificial templates (polystyrene sulfonate, PSS) with chitosan (CS) as the polycation and carboxymethyl chitosan (CMCS) as the polyanion, respectively. Their hollow structure was confirmed by the TEM analysis. The DLS analysis indicated that the multilayer chitosan microcapsules were pH and ionic strength dual-responsive. Due to the biocompatibility of the single component chitosan used, the multilayer chitosan microcapsules are expected to be used in the controlled release of drugs.     

侧链含5-氟尿嘧啶甲壳胺的合成及其抗肿瘤活性的研究

本文报道了以不同分子量的甲壳胺为载体,制备了侧链含5-氟尿嘧啶的一系列高分子载体药物;通过定氮分析测定了H_2N-基的反应率;由IR、UV和~(13)C-NMR确定了载体药物的结构;模拟生理条件考查了在不同pH的缓冲溶液中5-氟脲嘧啶或其衍生物的水解释放率。体外初步实验结果表明,具有Ⅰ和Ⅱ结构的载体药物对艾氏腹水癌细胞有较强的杀伤作用。     

Biodegradable biocompatible xyloglucan films for various applications

Polysaccharides are known for their film-forming properties which have been intensively investigated for food and non-food applications. Here we have developed a xyloglucan transparent film for various applications especially in controlled release of drugs and cosmetics. The present study evaluated the properties of the composite films of xyloglucan, chitosan and rice starch obtained by the casting/solvent evaporation method. Xyloglucan chitosan blend film shows better mechanical properties. Hydrophobicity and crystallinity of xyloglucan film was increased by blending with chitosan. This was confirmed by X-ray diffraction studies and contact angle measurements. Scanning electron microscopic observations indicated that the xyloglucan chitosan blend films were smooth and homogenous. Thermogravimetric and differential scannining calorimetric analysis showed a high thermal stability and melting temperature of xyloglucan chitosan film compared with others. The swelling properties of the xyloglucan chitosan blend film, studied as a function of pH showed that the sorption ability of the blend film was high at a pH 7.4. This indicates its controlled release property at that pH. Controlled drug release property of the film was studied by using streptomycin as a model drug.     

The influence of chitosan on in vitro properties of Eudragit RS microspheres

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.     

肽类药物口服剂型材料及控制释放性能研究Ⅰ.壳聚糖─海藻酸盐微囊对胰岛素的控释作用

应用壳聚糖-海藻酸盐微囊技术制备了一系列胰岛素微囊，并研究了不同反应条件如海藻酸钠浓度、壳聚糖浓度、壳聚糖分子量及壳聚糖溶液pH值对微囊的胰岛素包封率及其释放性能的影响。结果表明，海藻酸钠浓度越高，微囊对胰岛素的包封率越高，在模拟小肠液中释放速率越低；壳聚糖浓度越大，微囊的胰岛素包封率及其在模拟胃液中释放率越高，在模拟肠液中释放达最大值所需时间越长；而随壳聚糖分子量减小，微囊在胃液中释放率增高；壳聚糖溶液pH值的变化对微囊的胰岛素包封率未造成明显影响。