海藻酸钠壳聚糖微球作为药物载体的研究进展

海藻酸钠壳聚糖微球是具有生物粘附性且能结合和传递大分子药物的天然高分子材料,且在生物医学领域具有广阔应用前景的药物载体。它具有生物黏附性、生物相容性、生物可降解性、对人体无毒性且能够结合和传递大分子药物的天然高分子材料。海藻酸钠壳聚糖微球作为载药微球具有提高药物的生物利用度、延长药物的作用时间等优点。国内外近些年已将其应用于药剂学领域,以及将其作为药物载体经微球化与药物结合形成给药系统的研究也在逐步开展并取得了较多成果。本文主要阐述海藻酸钠壳聚糖微球的主要生物特性、作用特点及其在医学领域中应用的研究进展,并对其应用前景进行探讨。     

壳聚糖及其衍生物作为药物载体研究进展

壳聚糖是甲壳素脱乙酰化的衍生物,是自然界中唯一的碱性多糖.壳聚糖及其衍生物是一类资源丰富、可生物降解的天然聚合物,具有生物相容性、高电荷密度、无毒性和粘膜粘附性,广泛应用于生物医学和药物制剂领域.壳聚糖作为药物载体可以控制药物释放、提高药物疗效、降低药物毒副作用,可以提高疏水性药物对细胞膜的通透性和药物稳定性及改变给药途径,还可以加强制刑的靶向给药能力.本文分别从壳聚糖及其衍生物在大分子药物载体、缓控释系统及不同部位给药系统中的应用进行了综述,以说明壳聚糖及其衍生物是一种优良的药物传递载体和新型药用辅料.     

聚乳酸羟基乙酸纳米微球在肿瘤药物递送中的应用

药物递送载体的应用使得小分子药物、蛋白质药物,以及基因药物能够通过多种给药方式用于癌症的治疗。聚乳酸-羟基乙酸共聚物因其具有良好的生物相容性及生物可降解性,成为广泛采用的抗癌药物载体之一,可以通过静脉、皮下、口服等多种给药途径用于化疗、基因治疗、蛋白治疗给药及接种免疫等诸多方面,显示了良好的应用前景。     

微针用于生物大分子及纳米药物透皮给药的尝试与挑战

生物大分子及纳米药物,比如,亚单位疫苗、DNA疫苗、以及针对真皮层的治疗药物,作为近年来新兴的治疗药物,在有些治疗领域有着透皮给药的需求。由于具有靶向性高,疗效显著等特点,生物大分子及纳米药物逐渐成为新的研究热点。微针作为一种新型的给药技术,不仅具有无痛、给药方便等优点,而且运用物理手段可大幅提高大分子甚至纳米药物的透皮吸收及皮层靶向,能够避过胃肠道消化作用以及肝脏首过效用。将微针技术与生物大分子药物相结合,能够同时发挥两者的优势,实现高靶向生物药物的无痛给药。本文简述微针透皮给药技术、以及生物大分子给药的研究进展,对微针技术用于生物大分子及纳米药物透皮给药的尝试研究做了介绍和总结,对存在的技术挑战进行了分析和展望。     

蛋白质药物口服的研究进展

蛋白质药物口服给药系统因其给药方便、顺应性好,逐渐成为一种最有前景的给药方式.从提高蛋白质药物生物利用度入手,综述采用结构修饰、吸收促进剂、酶抑制剂、结肠定位释药、脉冲式药物给药系统和受体介导靶向载体系统等方式,均可大大提高蛋白质药物的口服生物利用度和在胃肠道中的稳定性.     

壳聚糖在给药系统中的应用

壳聚糖来源丰富,具有良好的生物相容性、生物可降解性、无毒性、成膜性和极强的可塑性,已经作为高分子材料,广泛用于给药系统中.将壳聚糖应用于给药系统中可以提高药物安全性、有效性及可靠性,可以调整药物释放速率,减少给药次数.此外,壳聚糖可塑性强,可制成膜、压成片、制成颗粒、微球或增粘剂等多种剂型.该文就壳聚糖的特性及其在给药系统中的应用予以综述.     

口服抗癌药物纳米载体的研究进展

实现抗癌药物的口服给药,对于癌症的化疗及患者的生活会有很大的方便性。但大多数抗癌药物直接口服给药时,由于受到胃肠道的屏蔽作用导致生物利用度降低,所以寻找一种有效的药物载体,对于实现抗癌药物的口服给药是至关重要的。纳米技术的出现,带动了纳米药物载体的发展,使得抗癌药物的口服给药有了很大的突破。对不同材料,主要包括合成高分子材料、天然高分子材料作为口服抗癌药物载体的特点以及体内体外的研究结果进行回顾和综述。     

纳米技术在药物靶向治疗方面的现状和应用前景

纳米技术应用于药物载体的研究一直是近年生物医学所关注的热点。纳米药物载体在实现靶向性给药、缓释药物、提高难溶性药物与多肽药物的生物利用度、降低药物的毒副作用等方面表现出明显的优势。本文就近些年常见的纳米载药体的种类及其特性、常用制备方法、靶向治疗方面的研究进行综述,并对未来发展前景进行展望。     

生物可降解聚合物纳米粒给药载体

生物可降解聚合物纳米粒用于给药载体具有广阔的前景。本文综述了生物可降解聚合物纳米粒给药载体领域的最新进展 :包括纳米粒表面修饰特性、药物释放、载多肽和蛋白质等生物大分子药物传输中的潜在应用。     

多糖-药物轭合物的研究与展望

多糖类物质作为赋形剂在药物制剂中已被广泛使用,多糖结构中包含了多种活性基团如羟基、羧基、氨基等,具有良好的亲水性、生物可降解性以及生物安全性,使其在聚合物-药物轭合物的构建中成为理想的载体材料.目前天然的多糖大分子及其衍生物作为药物载体的研究方兴未艾,以多糖为载体的聚合物-药物轭合物在定位或靶向给药、组织工程、生物黏附等领域也备受关注.本文以天然多糖-药物轭合物的研究现状为切入点,总结归纳了多糖-药物轭合物的设计与构建途径,介绍了其在药物传递中的应用,讨论并分析了多糖在轭合物体系中的角色和发挥的作用,对以多糖为载体的聚合物-药物轭合物发展的方向予以了讨论.     

Antibacterial Activity and Drug Release of Chitosan Sponge Containing Doxycycline Hyclate

The purpose of the present study was to develop and characterize the chitosan sponges loading with doxycycline hyclate and their antibacterial activities. The pore density of chitosan sponge prepared with freeze drying technique was increased as the higher concentrated chitosan solution was used. The sponge prepared from 10% w/w of the chitosan solution and crosslinking with glutaraldehyde solution was utilized for loading with doxycycline hyclate. The drug release and sustainable antibacterial activity of fabricated sponge were assessed using dissolution test and agar diffusion test, respectively. Drug release from non-crosslinked sponge into phosphate buffer pH7.4 was slower than that from crosslinked sponge since the former could absorb the medium and form gel to retard the initial drug diffusion. Sustainable antibacterial activity of developed sponge was evident against S. aureus and E. coli. In conclusion, the in vitro release profile and antibacterial efficiency indicated that doxycycline hyclate could be sustained using chitosan sponge.     

Preparation and characterization of sodium hexameta phosphate cross-linked chitosan microspheres for controlled and sustained delivery of centchroman

The cross-linked microspheres using chitosan with different molecular weights and degree of deacetylation have been prepared in presence of sodium hexameta polyphosphate (SHMP) as physical cross-linker. The degree of cross-linking through electrostatic interactions in chitosan microspheres has been evaluated by varying the charge density on chitosan and varying degree of dissociation of sodium hexameta polyphosphate by solution pH. The degree of deacetylation and molecular weight of chitosan has controlled electrostatic interactions between hexameta polyphosphate anions and chitosan, which played significant role in swelling, loading and release characteristics of chitosan microspheres for centchroman. The microspheres prepared by hexameta polyphosphate anions cross-linker were compact and more hydrophobic than covalently cross-linked microspheres, which has been attributed to the participation of all amino groups of chitosan in physical cross-linking with added hexameta polyphosphate anions. The microspheres prepared under different experimental conditions have shown an initial step of burst release, which was followed by a step of controlled release for centchroman. The extent of drug release in these steps has shown dependence on properties of chitosan and degree of cross-linking between chitosan and added polyanions. The degree of swelling and release characteristics of microspheres was also studied in presence of organic and inorganic salts, which shown significant effect on controlled characteristics of microspheres due to variations in ionic strength of the medium. The initial step of drug release has followed first order kinetics and become zero order after attaining an equilibrium degree of swelling in these microspheres. The microspheres prepared using chitosan with 62% (w/w) degree of deacetylation and molecular weight of 1134 kg mol⁻¹ have shown a sustained release for centchroman for 50 h at 4% (w/w) degree of cross-linking with SHMP.     

重组人生长激素长效缓释的研究进展

重组人生长激素长效缓释制剂可提高药物生物利用度,延长药物半衰期,减少药物不良反应,给疾病的临床治疗提供了更多的手段和可能。从微球、脂质体、化学修饰等方面综述了重组人生长激素长效缓释的研究进展。     

Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose

The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and 419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release. Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties, and drug release from the obtained pellets. Published: August 10, 2007     

Miscibility study of chitosan/2-hydroxyethyl starch blends and evaluation of their effectiveness as drug sustained release hydrogels

Polymeric matrices of chitosan (CS), 2-hydroxyethyl starch (HES) and their blends prepared by solvent evaporation technique, have been tested as sustained release hydrogels of ropinirole drug. X-Ray diffraction (XRD), infrared spectroscopy (FT-IR) and viscometry measurements showed that the two polymers can form miscible blends. This miscibility is owed to formed hydrogen bonds taking place between the reactive groups of CS and HES and one glass transition is recorded in all blends. Neat polymers were used to prepare solid dispersion formulations with ropinirole drug. It was found that drug was released immediately within 15-30 min from HES while the release was slower from CS matrix. Completely different were the release rates from ropinirole with physical mixtures using neat polymers and their blends. Due to the different solubility and swelling behaviour of CS and HES the release rates showed a sustained profile from the blends containing high amounts of CS.     

纳米微球药物缓释技术

纳米微球作为药物载体被越来越多地应用于医药领域,这一技术得到研究者的广泛重视。目前已有多种纳米微球制剂投入临床使用。纳米微球的深入研究具有重要的意义。我们概述了近年来纳米微球的研究及应用情况,展望了纳米微球药物载体缓释技术的应用前景及需要解决的问题。     

Poly(3-hydroxybutyrate)/chitosan/ketoprofen or piroxicam composite microparticles: Preparation and controlled drug release evaluation

Poly(3-hydroxybutyrate)/chitosan/piroxicam or ketoprofen composite microparticles were prepared by the solid-in-water-in-oil emulsion-solvent evaporation technique with the aim of reducing the burst effect and controlling the drug release. Reservoir-type microparticles, composed of poly(3-hydroxybutyrate) microspheres embedded in a chitosan matrix were prepared. The size and morphological characteristics of the composite microparticles were evaluated in relation to the chitosan concentration and cross-linking with glutaraldehyde. Reservoir-type composite microparticles were obtained using 2.0% and 3.0% w/v chitosan solutions. A significant reduction in the burst effect and prolonged drug release were observed, particularly when higher chitosan and glutaraldehyde concentrations were used.     

尺寸均一的壳聚糖微球的制备及其作为胰岛素控释载体的研究

采用新型微孔膜乳化技术制备了载胰岛素的壳聚糖微球。研究表明,要制备粒径均一的壳聚糖微球,必须将亲水性膜修饰成疏水性;制得的微球粒径和所采用的膜孔径之间存在很好的线性关系,使得微球粒径可控;以胰岛素为模型药物,主要考察了交联剂用量和交联时间对微球表面形态、药物包埋率和微球体外释药特性的影响。结果表明当氨基与醛基的摩尔比为1∶0.7、交联时间为1h时,所得载药微球的包埋率最高,随着戊二醛用量的增加和交联时间的延长,药物体外释放速率减慢。     

Chitosan magnetic nanoparticles for drug delivery systems

The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.     

Chitosan-Modified PLGA Nanoparticles with Versatile Surface for Improved Drug Delivery

Shortage of functional groups on surface of poly(lactide-co-glycolide) (PLGA)-based drug delivery carriers always hampers its wide applications such as passive targeting and conjugation with targeting molecules. In this research, PLGA nanoparticles were modified with chitosan through physical adsorption and chemical binding methods. The surface charges were regulated by altering pH value in chitosan solutions. After the introduction of chitosan, zeta potential of the PLGA nanoparticle surface changed from negative charge to positive one, making the drug carriers more affinity to cancer cells. Functional groups were compared between PLGA nanoparticles and chitosan-modified PLGA nanoparticles. Amine groups were exhibited on PLGA nanoparticle surface after the chitosan modification as confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The modified nanoparticles showed an initial burst release followed by a moderate and sustained release profile. Higher percentage of drugs from cumulative release can be achieved in the same prolonged time range. Therefore, PLGA nanoparticles modified by chitosan showed versatility of surface and a possible improvement in the efficacy of current PLGA-based drug delivery system.