透明质酸及其衍生物在药物递送系统中的研究进展

透明质酸(hyaluronic acid,HA)是一种天然多糖,具有良好的生物相容性和可降解性。天然HA对强酸、强碱、热、自由基及透明质酸酶敏感,对其进行修饰可克服以上问题并获得具有各种优良特性的衍生物。HA及其衍生物可作为药物的缓释载体,能够延缓药物的释放,发挥长效作用,可用于多种药物的递送,如蛋白质、核酸及抗肿瘤药物等。HA及其衍生物可与细胞表面多种受体(CD44,RHAMM,LYVE-1,HARE)特异性结合,可用于靶向药物递送,尤其是抗肿瘤药物的递送。     

壳聚糖及其衍生物在药物载体中的应用

摘 要壳聚糖及其衍生物具有无毒、良好的生物相容性和可降解性、黏膜黏附性和促渗性等优点,在药物载体领域具有较为广阔的研究及应用前景。本文结合国内外最新发表的相关文献,对壳聚糖及其衍生物作为相关药物载体的应用以及作用机制进行分析讨论,并对其作为抗肿瘤药物靶向载体、缓控释药物载体、眼用药物载体、基因载体和凝胶基质的应用及研究进展进行综述。     

壳多糖及其衍生物在动物细胞培养中的应用研究进展

壳多糖作为一种碱性天然多糖 ,由于其无毒且具有良好的生物及组织相容性而备受人们的重视 ,本文综述了壳多糖及其衍生物作为细胞培养微载体材料、生物微胶囊材料、基因转移载体、细胞培养生物因子及作为药物吸收促进因子 5个方面的研究进展。     

壳多糖及其衍生物在动物细胞培养中的应用研究进展

壳多糖作为一种碱性天然多糖,由于其无毒且具有良好的生物及组织相容性而备受人们的重视,本文综述了壳多糖及其衍生物作为细胞培养微载体材料、生物微胶囊材料、基因转移载体、细胞培养生物因子及作为药物吸收促进因子５个方面的研究进展。     

透明质酸衍生物在生物药品传递方面的研究进展

目的综述透明质酸衍生物的制备及近年来在生物药品传递方面的研究进展。方法参考国内外相关文献32篇,进行相关信息的分析、归纳和总结。结果阐述通过化学修饰透明质酸制备衍生物的方法和在传递基因和蛋白质等生物药品方面的应用。结论透明质酸衍生物在药物传递方面将会有广阔的发展的前景。     

多糖及其衍生物在药物传递系统中的应用研究新进展

多糖是一类生物相容性好、无毒、非免疫原性的生物材料,现已广泛应用于药物传递系统。综述海藻酸盐、几丁质、葡聚糖、透明质酸和肝素等多糖及其衍生物的理化和生物学特性以及在药物传递系统中的应用进展。     

透明质酸在紫杉醇新型给药系统中的应用

透明质酸是一种酸性黏多糖,其作为优良的药物载体,具有生物相容性良好,生物可降解的特性,同时可与肿瘤细胞表面富含的CD44、RHAMM等受体结合,目前已成为抗肿瘤药物递送载体研究的主要热点。本综述主要通过查阅近年文献,对透明质酸在紫杉醇新型给药系统中的应用进行综述。     

海藻酸钠及其衍生物在生物医药中的应用进展

目的:总结海藻酸钠及其衍生物在生物医药中的应用进展,为其临床应用与开发提供参考。方法:以"海藻酸钠""衍生物""组织工程""介入治疗""缓释""靶向""载体""Alginate""Derivative""Tissue engineering""Intervention""Control release""Target""Delivery"等为关键词,组合查询1990年1月-2019年4月在中国知网、维普网、ScienceDirect、PubMed等数据库中的相关文献,归纳海藻酸钠衍生物的种类,并从药物递送、创面修复、组织工程、介入治疗等4个方面总结海藻酸钠及其衍生物在生物医药中的应用进展。结果与结论:共检索到相关文献13 387篇,其中有效文献63篇。海藻酸钠衍生物包括基团衍生物(乙酰化衍生物、磷酸化衍生物、硫酸化衍生物)和接枝共聚物。在药物递送方面,海藻酸钠及其衍生物可作为缓控释药物载体、生物大分子载体、靶向给药载体递送药物;在创面修复方面,海藻酸钠及其衍生物可被开发为各类医用敷料,达到止血、抗菌、促进创面愈合等效果;在组织工程方面,海藻酸钠及其衍生物可作为细胞微囊化载体或支架材料,为细胞提供生长支撑的同时还可递送生物活性分子,在软骨、硬骨、皮肤组织修复方面应用广泛;在介入治疗方面,海藻酸钠及其衍生物可将血管栓塞介入治疗和靶向药物治疗相结合,实现药物局部富集,增强疗效。临床上海藻酸钠通常被制成水凝胶进行应用,但存在机械强度差、对疏水性分子负载量低、降解不易控制等缺点,通过乙酰化、磷酸化、硫酸化等形成相应的衍生物可扩大其应用范围,但海藻酸钠及其衍生物的应用仍然存在一些问题,如其力学性能和生物相容性还有待提高、产生的细胞毒性仍需降低,因此,在后续研究中还需深入挖掘海藻酸钠及其衍生物的应用潜能和安全性,为其临床应用提供依据。     

透明质酸修饰的空腔靶向纳米载体制备及其体内外性能评价

目的:制备具有pH响应性的透明质酸衍生物修饰的主动靶向载药空腔纳米球载体,并进行相关性能测定.方法:采用One-pot法制备空腔碳酸钙纳米球,并用透明质酸与壳聚糖的偶联物进行修饰,得到具有pH响应性的靶向给药载体;以阿霉素作为模型药物,对载体的粒径及Zeta电位、包封率、载药量及体外释放进行考察;以人肝癌HepG2细胞...     

环糊精及其衍生物的药学应用进展

环糊精及其衍生物通过非共价结合的包合作用或与药物形成共轭化合物,在提高溶解效率、改善药剂性能和方便药物传输等方面得到了广泛的应用.近年来,环糊精及其衍生物还被用作治疗性基因载体和某些蛋白质生物大分子的新型药物制剂材料,从而开辟了一个崭新的前沿研究领域.     

Hyaluronic acid and its derivatives in drug delivery and imaging: Recent advances and challenges

Hyaluronic acid (HA) is a biodegradable, biocompatible, nontoxic, and non-immunogenic glycosaminoglycan used for various biomedical applications. The interaction of HA with the CD44 receptor, whose expression is elevated on the surface of many types of tumor cells, makes this polymer a promising candidate for intracellular delivery of imaging and anticancer agents exploiting a receptor-mediated active targeting strategy. Therefore, HA and its derivatives have been most investigated for the development of several carrier systems intended for cancer diagnosis and therapy. Nonetheless, different and important delivery applications of the polysaccharide have also been described, including gene and peptide/protein drugs delivery. The aim of this review was to provide an overview of the existing recent literature on the use of HA and its derivatives for drug delivery and imaging. Notable attention is given to nanotheranostic systems obtained after conjugation of HA to nanocarriers as quantum dots, carbon nanotubes and graphene. Meanwhile, attention is also paid to some challenging aspects that need to be addressed in order to allow translation of preclinical models based on HA and its derivatives for drug delivery and imaging purposes to clinical testing and further their development.     

Feasibility Study of Pollen‐Shape Drug Carriers in Dry Powder Inhalation

The feasibility of using pollen‐shape carriers in dry powder inhalation is studied. Pollen‐shape hydroxyapatite (HA) particles are synthesized with a geometric diameter range from 21.1 to 48.6 µm and effective density range from 0.21 to 0.41 g/cm³. The flowability of the particles is characterized by the Carr's compressibility index (CI) and angle of slide (θ). The HA carriers are found to have better flowability than commonly used lactose (LA) carrier with similar size range. The HA carriers are also found to be capable of high drug attachment. The aerosolization and deposition properties of a model drug are compared using HA and LA as carriers. Results indicate that pollen‐shape HA carriers have good potential to be used as drug carrier in dry powder inhalation. It can give higher drug emission and respirable fraction than traditional LA carriers. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1309–1321, 2010     

Hyaluronan--a review of the recent patent literature

A review of patent literature surrounding the use of hyaluronan (HA) and its derivatives, or agents capable of modulating endogenous levels, is presented. Indications are many and varied and include arthritis, abnormal wound healing, neoplasia, prevention of surgical adhesions and dermatological disorders. In many cases, it is the physicochemical and biological properties of HA itself that have been exploited. For example, HA and/or its derivatives have been suggested as a synovial fluid replacement, a vehicle for topical application of drugs, a matrix for sustained drug release and a putative drug delivery system (targeting HA receptors at sites of pathology). In each of these examples, the lack of toxicity of HA and its biocompatability are important considerations.     

透明质酸纳米给药载体的研究进展

透明质酸(hyaluronic acid,HA)是一种天然多糖,具有无毒性、无免疫原性、无致炎性、生物相容性好、生物可降解等诸多优点,同时还具有靶向性,在药物载体领域广泛应用。本文综述了各种HA纳米给药载体的合成、物理化学特点和生物学性质,重点阐述了其体外靶向能力和体内分布,展望了其发展趋势和应用前景。     

透明质酸在肿瘤治疗药物新型给药系统中的应用

透明质酸（hyaluronic acid, HA）因其良好的理化性质和肿瘤靶向性,已作为药物载体或者靶向因子应用于肿瘤治疗的新型给药系统中,并成为肿瘤治疗研究的热点。本文主要对HA在新型给药系统的应用进行介绍。     

聚天冬酰胺及其衍生物在药物释放中的应用

综述了可生物降解的高分子材料聚天各酰胺及其衍生物作为载体在药物控制释放中的应用。     

Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor

The complex system involved in the synthesis, degradation and binding of the high molecular weight glycosaminoglycan hyaluronic acid (hyaluronan or HA) provides a variety of structures that can be exploited for targeted cancer therapy. In many cancers of epithelial origin there is an upregulation of CD44, a receptor that binds HA. In other cancers, HA in the tumor matrix is overexpressed. Both CD44 on cancer cells and HA in the matrix have been targets for anticancer therapy. Even though CD44 is expressed in normal epithelial cells and HA is part of the matrix of normal tissues, selective targeting to cancer is possible. This is because macromolecular carriers predominantly extravasate into the tumor and not normal tissue; thus CD44-HA targeted carriers administered intravenously localize preferentially into tumors. Anti-CD44 antibodies have been used in patients to deliver radioisotopes or mertansine for treatment of CD44 expressing tumors. In early phase clinical trials, patients with breast or head and neck tumors treated with anti-CD44 conjugates experienced stabilized disease. A dose-limiting toxicity was associated with distribution of the antibody-drug conjugate to the skin, a site in the body with a high level of CD44. HA has been used as a drug carrier and a ligand on liposomes or nanoparticles to target drugs to CD44 overexpressing cells. Drugs can be attached to HA via the carboxylate on the glucuronic acid residue, the hydroxyl on the N-acetylglucosamine or the reducing end which are located on a repeating disaccharide. Drugs delivered in HA-modified liposomes exhibited excellent antitumor activity both in vitro and in murine tumor models. The HA matrix is also a potential target for anticancer therapies. By manipulating the interaction of HA with cell surface receptors, either by degrading it with hyaluronidase or by interfering with CD44-HA interactions using soluble CD44 proteins, tumor progression was blocked. Finally, cytotoxic drugs or prodrug converting enzymes can be attached to the HA matrix to generate a cytotoxic fence around the tumor. This review describes how the complex interplay among cancer biology, the CD44-HA interaction, drug carriers and drug targeting has been used to improve anticancer therapies. As these approaches evolve, they hold forth the prospect of significantly improved targeted anticancer treatments.     

壳聚糖介导的靶向药物传递系统

目的:综述了以壳聚糖或其衍生物为基础的多种特殊靶向载体系统的研究现状。方法:以国内外近年有代表性的文献为依据,进行分析、整理和归纳。结果与结论:由于壳聚糖具有一些独特的物理和生物特性,并且通过修饰后增加了壳聚糖的一些性质,使其成为优良的药物载体,从而实现药物的靶向性。这一载体材料近年来逐渐受到重视,具有良好的开发和应用前景。     

壳聚糖及其衍生物在药物递送中的研究进展

壳聚糖是自然界中存在的唯一的带正电的碱性氨基多糖,具有来源丰富、无毒、低免疫原性、良好的生物可降解性和生物相容性等优点。壳聚糖的活性氨基和羟基,经各种化学修饰如羧基化、巯基化、季铵化、疏水修饰、长循环修饰和靶向修饰,可获得具有特殊功能特性的衍生物,广泛用作药物和基因的载体材料。是近年来药剂学领域的研究热点。本文就近年来壳聚糖及其衍生物在药物递送中的研究进展作一综述。