高分子药物及载体材料

高分子药物由于具有良好的生物降解性和生物相容性,可以控制药物释放速度,能够降低药物的毒副作用,减少抗药性,提高药物的稳定性和有效利用率,从而引起国内外广泛关注.本文从自身具有药理活性的高分子、高分子载体药物两个方面综述了近年来高分子药物及载体材料的研究进展.按化学结合力不同将高分子载体药物分为高分子前药和高分子络合物药...     

热敏性可降解高分子胶束药物载体的研究进展

近年来刺激响应性聚合物胶束作为一种极有潜力的纳米药物载体得到了越来越广泛的关注,也是高分子领域研究的热点。本文概述了载药高分子胶束的发展特点和应用面临的主要困境,主要总结了温度敏感性高分子及其胶束的类别和特点,并重点阐述了热敏性可降解高分子及其胶束药物载体的最新研究进展,探讨了高分子胶束药物载体进入临床应用面临的挑战和解决问题的一些简单思路,相信多功能化的稳定的温敏性可降解载药高分子胶束系统在解决临床治疗问题上前景光明。     

高分子化学键载药物体系的制备与应用研究进展

高分子化学键载药物体系具有良好的稳定性、优异的药物缓释性和特定药物的靶向性,近年来备受关注。通常,其制备方法既可以是单体先聚合再负载药物,也可以是单体先负载药物再聚合成高分子。本文按照制备方式进行分类,综述了近年来高分子化学键载药物体系的研究现状。由于生物可降解高分子作为载体在高分子化学键载药物体系的应用中具有体内可降解、避免二次手术等优势,先键载后聚合的制备法具有流程简单、方法便捷、载药量高等优势,它们是目前高分子化学键载药物体系的重要发展方向。其中,集载体制备和药物键载于一体的一步法制备生物降解材料基化学键载药物,特别值得关注。     

蛋白质高分子药物载体研究进展

作为一类具有独特优势的生物高分子,蛋白质具有很好的生物相容性、生物可降解性、生物稳定性、极低的细胞毒性,且具有较高的载药性。在现有的多种药物载体中,基于动物蛋白的药物载体是最有潜力和值得关注的载药系统。常用于药物载体的动物蛋白中,使用较多的是白蛋白、胶原蛋白、乳清蛋白、角蛋白等。本文就几类重要的动物蛋白质载体的研究进展进行综述,并指出蛋白质高分子药物载体的发展方向。     

天然高分子药物微球载体材料的研究进展

综述了国内外在天然高分子药物微球载体材料研究及应用中的进展状况,主要从天然高分子药物微球载体材料的分类、微球的制备方法及特点、载药微球的给药途径和应用等进行概括,并对目前所存在的问题进行了描述。     

甲基乙烯基亚砜的合成

含亚砜基功能高分子可用作高分子药物载体,高分子螯合剂,高分子催化剂及气体分离膜材料等,近年来已引起各国学者的兴     

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。     

控制药物释放体系及其机理

药物控制释放是目前药物学发展的一个重要领域,用于药物控制释放的载体一般是高分子材料。本文主要介绍药物控制释放的种类、机理、高分子材料及其应用。     

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

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,而且还影响和控制药物的缓释机理。文章为第一部分,主要介绍生物高分子材料在药物传递系统中的降解机理与表征方法。     

高分子包囊药物释放体系

用高分子作为载体的高分子微包囊和纳米级包囊药物制剂不仅能控制药物以一定的速度释放，而且可对生物体的生理指标变化作出反馈，因而可以成为靶向药物释放体系。通过用高分子包囊还可以延长蛋白质和多肽类药物的生理活性，提高药物稳定性，使之成为长效药物，并使一些难以口服的药物能够制成口服制剂。文章在介绍有关高分子药物释放体系的一些基本原理，以及与之相关的药学、药理学、物理化学和高分子材料科学方面知识的基础上，较全面地综述了高分子包囊药物的制备技术和应用。阐述了高分子包囊的粒径、表面积、孔度、药物性能和药含量，以及高分子包囊材料的性能对药物释放行为的影响。对药物传送机理亦进行了扼要的介绍。     

Polymers for targeted and/or sustained drug delivery

Recent advances in the use of polymers for passive targeting of drugs attached or incorporated into polymeric species (enhanced permeability and retention, EPR) as well as active targeting of drugs by ligands or antibodies of receptors overexpressed on the surface of the targeted cells, is discussed in the present review. Examples of sustained, slow release of a drug incorporated into a polymeric matrix are cited. Drugs used for passive modes of targeting have been described in the context of polymer‐drug conjugates, drugs in the polymer coated liposomes, and drugs inserted into polymeric micelles. Active targeting of the drugs and their internalization by receptors, on the surface of the targeted cells, was also discussed. Release of the drugs inside cells, after are broken the environmentally sensitive links attaching them to polymeric platforms was described. Examples illustrate targeting drug by local heat generated by ultrasound, or by photodynamic treatment. Delivery modes of drugs incorporated into other nanoparticles and the concept of prodrugs have been investigated. Copyright © 2008 John Wiley & Sons, Ltd.     

Mechanochemical solid-state polymerization (XI): effect of water-insoluble pharmaceutical aids on drug release from mechanically synthesized polymeric prodrugs

We discuss here the effect of water-insoluble pharmaceutical aids on the nature of drug release from composite polymeric prodrugs synthesized by mechanochemical solid-state polymerization. Magnesium stearate (Mgst) and hydrogen castor oil (HCO) were used as water-insoluble pharmaceutical aids. Composite polymeric prodrugs were synthesized by the mechanochemical solid-state polymerization of a vinyl monomer of 5-fluorouracil (I) in the presence of Mgst or HCO. The molecular weight of the resulting polymeric prodrugs increased with increasing the content of Mgst or HCO. Prodrug hydrolysis was carried out in a heterogeneous system in phosphate buffer at pH 6.8 and 37 degrees C. The rate of drug release from the composite polymeric prodrug containing Mgst (Poly-Mgst) was faster than that from polymeric prodrug containing no pharmaceutical aids (Poly-Non), while hydrolysis of the composite polymeric prodrug containing HCO (Poly-HCO) was slower than Poly-Non. Scanning electron microscope (SEM) photos showed the surface of Poly-HCO was smoother than that of Poly-Non and Poly-Mgst. It was suggested that the slower drug release from Poly-HCO may be responsible for the smaller specific surface area than that of Poly-Non. It was also shown that the rate of drug release from the composite polymeric prodrugs decreases with increasing the content of Mgst or HCO. Hence, novel composite polymeric prodrugs with a variety of drug release rates can be prepared by mechanochemical solid-state polymerization in a totally dry process.     

Application of thermal analysis to the study of lipidic prodrug incorporation into nanocarriers

Anti HIV molecules as numerous drugs cannot efficiently penetrate into the brain. Prodrug synthesis and encapsulation into pegylated nanocarriers have been proposed as an approach for brain delivery. Pegylated polymeric nanoparticles and liposomes were chosen to incorporate glycerolipidic prodrugs of didanosine. Differential scanning calorimetry experiments were performed on mixtures of prodrugs and lipids or polymer in order to study their interaction. The optimal incorporation ratios were determined for each prodrug and compared for both types of nanocarriers. All these results would be used to prepare optimised formulations of didanosine prodrugs loaded into pegylated nanocarriers for brain drug delivery.     

In vitro and in vivo evaluation of microparticulate drug delivery systems composed of macromolecular prodrugs

Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.     

含葡糖基酮洛芬乙烯醇酯共聚物的合成及其药物释放性能

分别利用化学法和酶促法合成了酮洛芬乙烯酯和葡萄糖丁二酸乙烯酯（6-O-乙烯丁二酰-D-葡萄糖）2种聚合单体,通过2种单体的自由基聚合反应制备了具有较高分子量的酮洛芬葡萄糖共聚物前药,通过IR、NMR对聚合物的结构进行了表征,用GPC方法测定共聚物分子量。 研究了聚合单体投料比例对共聚物分子量和载药量的影响。 结果表明,随着药物乙烯酯在投料中比例的增加,聚合物前药的分子量逐渐下降,聚合物中酮洛芬的载药量逐渐增加。 酮洛芬含糖聚合物前药的体外释放研究表明,酮洛芬的释放时间大大延长,达到了缓释的目的,释药速率随着聚合物前药中葡萄糖含量增加而加快。 聚合物前药的释放动力学模拟结果显示,共聚物释药更符合一级动力学释放模型。     

Facile preparation of pH-responsive PEGylated prodrugs for activated intracellular drug delivery

The acid-cleavable amphiphilic prodrug DOX-PEG-DOX self-assemble to form nanoparticles and enter the cell by endocytosis for the pH-triggered intracellular delivery of DOX.     

Facile preparation of pH-responsive PEGylated prodrugs for activated intracellular drug delivery

PEGylated prodrug, covalent attaching polyethylene glycol (PEG) polymer chains to therapeutic drugs, is one of the most promising techniques to improve the water-solubility, stability, and therapeutic effect of drugs. In this study, three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights, were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin (DOX). This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution. The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. It turned out that the nanoparticles could be kept stable in the physiological environment, but degraded in acidic medium. Subsequently, we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property. The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells, which have the potential for use in cancer therapy.     

PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA–docetaxel conjugates

Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs, but suffers from poor compatibility between drugs and nanocarriers. Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines. However, the influence of hydrophobic length o...     

Lipases,liposomes and lipid-prodrugs

Colloidal and interfacial phenomena lie at the core of drug formulation, drug delivery, as well as drug binding and action at diseased sites, e.g., in cancer therapy. We review a class of liposome-based drug-delivery systems whose design and functional properties are intimately controlled by the stability of sub-micron structures, lipid-bilayer interfaces, and interfacially activated enzymes that can be exploited to target and deliver drugs. Moreover these drugs can themselves be special lipid molecules in the form of lipid prodrugs that both form the liposomal carrier as well as the substrate for endogenously upregulated lipases that turn the prodrugs into potent drugs precisely at the diseased site.